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BMC Musculoskeletal Disorders Jun 2024Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is...
BACKGROUND
Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is still largely unknown. In this study, we aim to evaluate the predictive power of different ML algorithms in this area and identify key features associated with the risk of subsequent fragility fractures in osteoporotic patients.
METHODS
We retrospectively analyzed data from patients presented with fragility fractures at our Fracture Liaison Service, categorizing them into index fragility fracture (n = 905) and subsequent fragility fracture groups (n = 195). We independently trained ML models using 27 features for both male and female cohorts. The algorithms tested include Random Forest, XGBoost, CatBoost, Logistic Regression, LightGBM, AdaBoost, Multi-Layer Perceptron, and Support Vector Machine. Model performance was evaluated through 10-fold cross-validation.
RESULTS
The CatBoost model outperformed other models, achieving 87% accuracy and an AUC of 0.951 for females, and 93.4% accuracy with an AUC of 0.990 for males. The most significant predictors for females included age, serum C-reactive protein (CRP), 25(OH)D, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), femoral neck Z-score, menopause age, number of pregnancies, phosphorus, calcium, and body mass index (BMI); for males, the predictors were serum CRP, femoral neck T-score, PTH, hip T-score, BMI, BUN, creatinine, alkaline phosphatase, and spinal Z-score.
CONCLUSION
ML models, especially CatBoost, offer a valuable approach for predicting subsequent fragility fractures in osteoporotic patients. These models hold the potential to enhance clinical decision-making by supporting the development of personalized preventative strategies.
Topics: Humans; Male; Female; Machine Learning; Aged; Retrospective Studies; Osteoporotic Fractures; Middle Aged; Aged, 80 and over; Predictive Value of Tests; Risk Assessment; Risk Factors; Osteoporosis; Algorithms
PubMed: 38834975
DOI: 10.1186/s12891-024-07559-y -
Calcified Tissue International Jun 2024Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to... (Review)
Review
Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.
PubMed: 38833001
DOI: 10.1007/s00223-024-01227-y -
BMC Public Health Jun 2024This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality...
BACKGROUND
This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality outcomes in hemodialysis patients during this Omicron surge.
METHODS
According to whether they are infected, they are divided into two groups: SARS-CoV-2-positive and SARS-CoV-2-negative. The SARS-CoV-2-positive group was divided into a survival group and a non-survival group for comparison.
RESULTS
366 of 457 hemodialysis patients were infected with SARS-CoV-2. The most common symptoms observed were fever (43.2%) and cough (29.8%), Followed by diarrhea (1.4%). Hemodialysis patients with hypertension were more susceptible to SARS-CoV-2 infection. The lymphocyte count, serum creatinine, serum potassium, and serum phosphorus in the SARS-CoV-2-positive group were significantly lower than those in the SARS-CoV-2-negative group. The all-cause mortality rate for infection with SARS-CoV-2 was 5.2%. Only 7 of 366 SARS-CoV-2-positive patients were admitted to the intensive care unit, but 6 of them died. Intensive care unit hospitalization rates were significantly higher in the non-survival group compared with the survival group. White blood cells count, neutrophil count, C-reactive protein, AST, and D-dimer in the non-survival group were higher than those in the survival group. The lymphocyte count, hemoglobin concentration, serum creatinine, serum albumin, serum phosphorus and parathyroid hormone in the non-survival group were lower than those in the survival group. Age > 65 years, elevated C-reactive protein and AST are independent risk factors for death. Finally, no significant difference in vaccination status was found between the SARS-CoV-2-positive group and the negative group.
CONCLUSIONS
Hemodialysis patients are at high risk for SARS-CoV-2 infection. Ensuring the adequacy of hemodialysis treatment and maintaining good physical condition of patients are the top priorities.
Topics: Humans; COVID-19; Renal Dialysis; Male; Female; Middle Aged; Aged; SARS-CoV-2; Adult; Kidney Failure, Chronic; Hospitalization
PubMed: 38831260
DOI: 10.1186/s12889-024-18999-5 -
Terapevticheskii Arkhiv Jun 2024To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA).
AIM
To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA).
MATERIALS AND METHODS
The study included 173 women with RA (age 61.0 [56.0; 66.0] years). A survey, dual-energy X-ray absorptiometry to measure the BMD of the lumbar spine (L-L), femoral neck (FN) and total hip (TH), routine blood chemistry, measurement of C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies (CCPA), parathyroid hormone (PTH), vitamin D, myostatin, follistatin, interleukin-6 (IL-6), IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, and tumor necrosis factor SF12 were performed.
RESULTS
PTH (β=-0.22, -0.35 and -0.30 for L-L, FN and TH, respectively), CRP (β=-0.18, 0.23 and -0.22 for L-L, FN and TH, respectively) and leptin (β=0.35, 0.32 and 0.42 for L-L, FN and TH, respectively) were shown a significant association with BMD in all sites of measurement. It was independent of age, body mass index and postmenopause duration. Associations were also found between adiponectin and BMD of L-L and TH (β=-0.36 and -0.28, respectively), CCPA and BMD of FN and TH (β=-0.21, -0.24, respectively) and IL-6 and BMD of FN (β=0.37).
CONCLUSION
The study of biochemical and immunological markers in women with RA demonstrated that CRP, CCPA, PTH, IL-6, adiponectin, and leptin influenced BMD.
Topics: Humans; Female; Arthritis, Rheumatoid; Bone Density; Middle Aged; Biomarkers; Absorptiometry, Photon; Aged; Postmenopause; C-Reactive Protein; Adiponectin; Osteoporosis, Postmenopausal; Leptin
PubMed: 38829811
DOI: 10.26442/00403660.2024.05.202705 -
Therapeutic Apheresis and Dialysis :... Jun 2024The aim of this study was to determine the level of frailty in older hemodialysis patients and to examine the relationship between their functional capacity, depression,...
INTRODUCTION
The aim of this study was to determine the level of frailty in older hemodialysis patients and to examine the relationship between their functional capacity, depression, and laboratory variables.
METHOD
This was a cross-sectional study, and the data were collected 243 dialysis patients aged 65 and over between May 2021 and May 2022.
RESULTS
The frailty rate was 49%. A statistically significant positive correlation was found between the frailty and age, hemodialysis vintage, and the number of hospitalizations. The frailty was negatively correlated with body mass index, Kt/V, Albumin, and parathyroid hormone. There was a statistically significant positive correlation between frailty and depression and a negative correlation between functional capacity.
CONCLUSION
A relationship was found between frailty and depression, functional capacity, and laboratory variables. In addition, the variables affecting the level of frailty in geriatric dialysis patients included dialysis vintage, dialysis adequacy, number of hospitalizations, albumin level, and patient weight.
PubMed: 38828537
DOI: 10.1111/1744-9987.14164 -
Journal of Lipid and Atherosclerosis May 2024This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease...
OBJECTIVE
This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD).
METHODS
The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques.
RESULTS
CAC patients had considerably higher levels of TNF-α (<0.001), IL-6 (<0.001), hs-CRP (=0.006), TC, TG, parathyroid hormone (PTH) (<0.001) and phosphorus (<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (=0.046), age (=0.009), TNF-α (=0.027), IL-6 (=0.005), TG (=0.002), PTH (=0.002), and phosphorus (=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (=0.045).
CONCLUSION
Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.
PubMed: 38826181
DOI: 10.12997/jla.2024.13.2.194 -
Archives of Medical Research Jun 2024Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions...
BACKGROUND
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up.
OBJECTIVE
To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors.
METHODS
Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons.
RESULTS
Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine.
CONCLUSIONS
More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.
Topics: Humans; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Phenotype; Parathyroid Hormone; Phosphorus; Vitamin D; Renal Dialysis; Renal Insufficiency, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder; Calcium
PubMed: 38824883
DOI: 10.1016/j.arcmed.2024.103008 -
Nature Communications Jun 2024Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological...
Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling ("biased agonism") with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present an approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
Topics: Ligands; Humans; Receptor, Parathyroid Hormone, Type 1; Single-Domain Antibodies; HEK293 Cells; Signal Transduction; Receptors, G-Protein-Coupled; Protein Binding; Animals; Peptides
PubMed: 38824166
DOI: 10.1038/s41467-024-49068-5 -
Scientific Reports May 2024The close link between intestinal microbiota and bone health ('gut-bone' axis) has recently been revealed: the modulation of the amount and nature of bacteria present in...
The close link between intestinal microbiota and bone health ('gut-bone' axis) has recently been revealed: the modulation of the amount and nature of bacteria present in the intestinal tract has an impact on bone health and calcium (Ca) metabolism. Probiotics are known to favorably impact the intestinal microbiota. The objective of this study was to investigate the effect of Pediococcus acidilactici CNCM I-4622 (PA) on laying performance, egg/eggshell quality, Ca metabolism and bone mineralization and resistance in relatively old layers (50 wks old at the beginning of the experiment) during 14 weeks. 480 Hy Line brown layers were divided into 2 groups (CON and PA: 3 layers/rep, 80 rep/group) and fed with a diet formulated to be suboptimal in calcium (Ca) and phosphorus (P) (- 10% of the requirements). The total egg weight was improved by 1.1% overall with PA, related to an improvement of the weight of marketable eggs (+ 0.9%). PA induced a decreased % of downgraded eggs, mainly broken eggs (- 0.4 pts) and FCR improvement (- 0.8% for all eggs, - 0.9% for marketable eggs). PA also led to higher Haugh units (HU: + 7.4%). PA tended to decrease crypt depth after the 14 weeks of supplementation period in the jejunum (- 25.2%) and ileum (- 17.6%). As a consequence, the VH/CD ratio appeared increased by PA at the end of the trial in the jejunum (+ 63.0%) and ileum (+ 48.0%). Ca and P retention were increased by 4 pts following PA supplementation, translating into increased bone hardness (+ 19%), bone cohesiveness (+ 43%) and bone Ca & P (+ 1 pt) for PA-supplemented layers. Blood Ca and P were respectively improved by 5% and 12% with PA. In addition, blood calcitriol and osteocalcin concentrations were respectively improved by + 83% and + 3% in PA group at the end of the trial, compared to CON group. There was no difference between the 2 groups for ALP (alkaline phosphatase) and PTH (parathyroid hormone). PA significantly decreased the expression of the following genes: occludin in the small intestine, calbindin 1 in the ovarian tissue and actin B in the bone. PA therefore improved zootechnical performance of these relatively old layers, and egg quality. The parallel increase in Ca and P in the blood and in the bone following PA supplementation suggests an improvement of the mineral supply for eggshell formation without impacting bone integrity, and even increasing bone resistance.
Topics: Animals; Probiotics; Pediococcus acidilactici; Chickens; Phosphorus; Calcium; Female; Dietary Supplements; Animal Feed; Eggs; Oviposition; Gastrointestinal Microbiome
PubMed: 38821966
DOI: 10.1038/s41598-024-62779-5 -
Journal of Clinical Pathology May 2024This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and...
AIMS
This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and calcium levels.
METHODS
A historical cohort study was conducted on adult patients with solitary PTA removed in the Gold Coast Health Precinct, Australia, between 2017 and 2022.
RESULTS
PTA weight is correlated with the change in day 1 PTH level (r=0.26, p=0.036), the change in day 1 corrected calcium level (r=0.20, p=0.033), and the change in follow-up corrected calcium level (r=0.47, p<0.001). The largest dimension (size) of PTA is also correlated with the change in day 1 PTH (r=0.30, p=0.011) and the change in follow-up corrected calcium level (r=0.40, p<0.001). Adjusted for age and gender, a statistically significant negative correlation was found between day 1 PTH level and adenoma size, resulting in a 0.5% change in size for every percentage change in PTH level (equating to a 5.0% increase in variance explained, p=0.038). Similarly, a negative correlation was identified in day 1 corrected calcium levels and weight, with a 4.7% change in weight for every percentage of change in day 1 corrected calcium level (an increase of 5.6% variance explained, p=0.010). In addition, a negative correlation was identified, where every 3.1% change in size (an increase of 17.4% variance explained, p<0.001) and 7.6% change in weight (an increase of 22.7% variance explained, p<0.001) was seen with every percentage change in follow-up corrected calcium levels. Clear-cell PTA had the most significant percentage fall in day 1 corrected calcium levels compared with other PTA subtypes (p=0.007).
CONCLUSIONS
Preoperative calcium and PTH levels correlate with PTA weight and size. The degree of change in postoperative corrected calcium levels behaved differently in the clear-cell subtype.
PubMed: 38821854
DOI: 10.1136/jcp-2023-209340