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The Iowa Orthopaedic Journal 2024
The 2024 Michael Bonfiglio Award for Student Research in Orthopaedic Surgery The 2024 Iowa Orthopaedic Society Medical Student Research Award for Musculoskeletal Research.
PubMed: 38919340
DOI: No ID Found -
Cell Reports Jun 2024With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23),...
With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-β-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes. The D enantiomer, described to be elevated with exercise in humans, can also induce Fgf23 but through a delayed, indirect process via sclerostin. The two enantiomers both signal through the same receptor, Mas-related G-protein-coupled receptor type D, but activate distinct signaling pathways; L-BAIBA increases Fgf23 through Gαs/cAMP/PKA/CBP/β-catenin and Gαq/PKC/CREB, whereas D-BAIBA increases Fgf23 indirectly through sclerostin via Gαi/NF-κB. In vivo, both enantiomers increased Fgf23 in bone in parallel with elevated urinary phosphate excretion. Thus, exercise-induced increases in BAIBA and FGF23 work together to maintain phosphate homeostasis.
PubMed: 38935499
DOI: 10.1016/j.celrep.2024.114397 -
Frontiers in Pharmacology 2024Polypharmacy, the use of multiple medications, is a growing concern among middle-aged and older patients, posing potential risks and challenges in healthcare management.
INTRODUCTION
Polypharmacy, the use of multiple medications, is a growing concern among middle-aged and older patients, posing potential risks and challenges in healthcare management.
AIM
This study aimed to identify the prevalence of polypharmacy and hyper-polypharmacy among populations of middle-aged vs older patients and identify its associated common comorbidities and prescribed medications in Qatif Central Hospital (QCH), Saudi Arabia.
METHODS
Patients aged 40 years or older who presented to an outpatient medical care clinic at QCH, Saudi Arabia, between 1 January and 31 December 2021 were included, and their comorbidities, prescribed medications, and recent clinical laboratory test results were collected. The Charlson comorbidity index (CCI) score was calculated to predict the risk of mortality. Logistic regression was used to compute the association between the prevalence of polypharmacy and patient characteristics. The results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs).
RESULTS
A total of 14,081 patients were included; 31% of the cohort comprised older patients, and 66% of the cohort was identified with polypharmacy. The majority of the polymedicated patients were presented to an internal medicine care unit (34%). The prevalence of polypharmacy was positively associated with CCI (OR = 3.4, 95% CI 3.3-3.6), having a disease related to the musculoskeletal system (MSD) (OR = 4.2, 95% CI 3.8-4.7), and alimentary tract and metabolism (ATM) (OR = 3.8, 95% CI 3.4-4.2). Conversely, the prevalence of polypharmacy was negatively associated with age (OR = 0.9, 95% CI 0.89-0.91) and patients with cardiovascular diseases (OR = 0.6, 95% CI 0.5-0.7).
CONCLUSION
Polypharmacy is still an ongoing concern. Patients, particularly those with diseases related to MSD or ATM, should be considered for reviewing prescriptions by pharmacists to reduce the risk of adverse drug reactions and future consequences of polypharmacy.
PubMed: 38933679
DOI: 10.3389/fphar.2024.1357171 -
Frontiers in Bioengineering and... 2024Achieving an adequate level of detail is a crucial part of any modeling process. Thus, oversimplification of complex systems can lead to overestimation,...
Achieving an adequate level of detail is a crucial part of any modeling process. Thus, oversimplification of complex systems can lead to overestimation, underestimation, and general bias of effects, while elaborate models run the risk of losing validity due to the uncontrolled interaction of multiple influencing factors and error propagation. We used a validated pipeline for the automated generation of multi-body models of the trunk to create 279 models based on CT data from 93 patients to investigate how different degrees of individualization affect the observed effects of different morphological characteristics on lumbar loads. Specifically, individual parameters related to spinal morphology (thoracic kyphosis (TK), lumbar lordosis (LL), and torso height (TH)), as well as torso weight (TW) and distribution, were fully or partly considered in the respective models according to their degree of individualization, and the effect strengths of these parameters on spinal loading were compared between semi- and highly individualized models. T-distributed stochastic neighbor embedding (T-SNE) analysis was performed for overarching pattern recognition and multiple regression analyses to evaluate changes in occurring effects and significance. We were able to identify significant effects ( < 0.05) of various morphological parameters on lumbar loads in models with different degrees of individualization. Torso weight and lumbar lordosis showed the strongest effects on compression ( ≈ 0.9) and anterior-posterior shear forces ( ≈ 0.7), respectively. We could further show that the effect strength of individual parameters tended to decrease if more individual characteristics were included in the models. The induced variability due to model individualization could only partly be explained by simple morphological parameters. Our study shows that model simplification can lead to an emphasis on individual effects, which needs to be critically assessed with regard to complexity. At the same time, we demonstrated that individualized models representing a population-based cohort are still able to identify relevant influences on spinal loading while considering a variety of influencing factors and their interactions.
PubMed: 38933541
DOI: 10.3389/fbioe.2024.1363081 -
Frontiers in Immunology 2024This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize...
BACKGROUND
This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize the assessment of immunotherapy response.
METHODS
A training set comprising 305 HCC cases was obtained from The Cancer Genome Atlas (TCGA) database. Initially, a screening process was undertaken to identify prognostically significant immune-related genes (IRGs), followed by the application of logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods for gene modeling. Subsequently, the final model was constructed using support vector machines-recursive feature elimination (SVM-RFE). Following model evaluation, quantitative polymerase chain reaction (qPCR) was employed to examine the gene expression profiles in tissue samples obtained from our cohort of 54 patients with HCC and an independent cohort of 231 patients, and the prognostic relevance of the model was substantiated. Thereafter, the association of the model with the immune responses was examined, and its predictive value regarding the efficacy of immunotherapy was corroborated through studies involving three cohorts undergoing immunotherapy. Finally, the study uncovered the potential mechanism by which the model contributed to prognosticating HCC outcomes and assessing immunotherapy effectiveness.
RESULTS
SVM-RFE modeling was applied to develop an OS prognostic model based on six IRGs (CMTM7, HDAC1, HRAS, PSMD1, RAET1E, and TXLNA). The performance of the model was assessed by AUC values on the ROC curves, resulting in values of 0.83, 0.73, and 0.75 for the predictions at 1, 3, and 5 years, respectively. A marked difference in OS outcomes was noted when comparing the high-risk group (HRG) with the low-risk group (LRG), as demonstrated in both the initial training set (0.0001) and the subsequent validation cohort (0.0001). Additionally, the SVMRS in the HRG demonstrated a notable positive correlation with key immune checkpoint genes (CTLA-4, PD-1, and PD-L1). The results obtained from the examination of three cohorts undergoing immunotherapy affirmed the potential capability of this model in predicting immunotherapy effectiveness.
CONCLUSIONS
The HCC predictive model developed in this study, comprising six genes, demonstrates a robust capability to predict the OS of patients with HCC and immunotherapy effectiveness in tumor management.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Immunotherapy; Prognosis; Biomarkers, Tumor; Male; Female; Transcriptome; Middle Aged; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Support Vector Machine; Treatment Outcome
PubMed: 38933262
DOI: 10.3389/fimmu.2024.1371829 -
Pharmaceutics May 2024Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and...
Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.
PubMed: 38931826
DOI: 10.3390/pharmaceutics16060702 -
Sensors (Basel, Switzerland) Jun 2024The present pilot study aimed to propose an innovative scale-independent measure based on electroencephalographic (EEG) signals for the identification and quantification...
OBJECTIVE
The present pilot study aimed to propose an innovative scale-independent measure based on electroencephalographic (EEG) signals for the identification and quantification of the magnitude of chronic pain.
METHODS
EEG data were collected from three groups of participants at rest: seven healthy participants with pain, 15 healthy participants submitted to thermal pain, and 66 participants living with chronic pain. Every 30 s, the pain intensity score felt by the participant was also recorded. Electrodes positioned in the contralateral motor region were of interest. After EEG preprocessing, a complex analytical signal was obtained using Hilbert transform, and the upper envelope of the EEG signal was extracted. The average coefficient of variation of the upper envelope of the signal was then calculated for the beta (13-30 Hz) band and proposed as a new EEG-based indicator, namely Piq, to identify and quantify pain.
MAIN RESULTS
The main results are as follows: (1) A Piq threshold at 10%, that is, Piq ≥ 10%, indicates the presence of pain, and (2) the higher the Piq (%), the higher the extent of pain.
CONCLUSIONS
This finding indicates that Piq can objectively identify and quantify pain in a population living with chronic pain. This new EEG-based indicator can be used for objective pain assessment based on the neurophysiological body response to pain.
SIGNIFICANCE
Objective pain assessment is a valuable decision-making aid and an important contribution to pain management and monitoring.
Topics: Humans; Electroencephalography; Pilot Projects; Male; Female; Adult; Chronic Pain; Pain Measurement; Middle Aged; Signal Processing, Computer-Assisted; Young Adult
PubMed: 38931657
DOI: 10.3390/s24123873 -
Sensors (Basel, Switzerland) Jun 2024For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated...
For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated position. Functional neuromuscular stimulation (FNS) can restore seated posture and other motor functions after paralysis by applying small electrical currents to the peripheral motor nerves. In particular, the Networked Neuroprosthesis (NNP) is a fully implanted, modular FNS system that is also capable of capturing information from embedded accelerometers for measuring trunk tilt for feedback control of stimulation. The NNP modules containing the accelerometers are located in the body based on surgical constraints. As such, their exact orientations are generally unknown and cannot be easily assessed. In this study, a method for estimating trunk tilt that employed the Gram-Schmidt method to reorient acceleration signals to the anatomical axes of the body was developed and deployed in individuals with SCI using the implanted NNP system. An anatomically realistic model of a human trunk and five accelerometer sensors was developed to verify the accuracy of the reorientation algorithm. Correlation coefficients and root mean square errors (RMSEs) were calculated to compare target trunk tilt estimates and tilt estimates derived from simulated accelerometer signals under a variety of conditions. Simulated trunk tilt estimates with correlation coefficients above 0.92 and RMSEs below 5° were achieved. The algorithm was then applied to accelerometer signals from implanted sensors installed in three NNP recipients. Error analysis was performed by comparing the correlation coefficients and RMSEs derived from trunk tilt estimates calculated from implanted sensor signals to those calculated via motion capture data, which served as the gold standard. NNP-derived trunk tilt estimates exhibited correlation coefficients between 0.80 and 0.95 and RMSEs below 13° for both pitch and roll in most cases. These findings suggest that the algorithm is effective at estimating trunk tilt with the implanted sensors of the NNP system, which implies that the method may be appropriate for extracting feedback signals for control systems for seated stability with NNP technology for individuals who have reduced control of their trunk due to paralysis.
Topics: Humans; Algorithms; Accelerometry; Torso; Spinal Cord Injuries; Neural Prostheses; Posture
PubMed: 38931600
DOI: 10.3390/s24123816 -
Pharmaceuticals (Basel, Switzerland) May 2024Pirfenidone and Nintedanib are specific drugs used against idiopathic pulmonary fibrosis (IPF) that showed efficacy in non-IPF fibrosing interstitial lung diseases... (Review)
Review
Pirfenidone and Nintedanib are specific drugs used against idiopathic pulmonary fibrosis (IPF) that showed efficacy in non-IPF fibrosing interstitial lung diseases (ILD). Both drugs have side effects that affect patients in different ways and have different levels of severity, making treatment even more challenging for patients and clinicians. The present review aims to assess the effectiveness and potential complications of Pirfenidone and Nintedanib treatment regimens across various ILD diseases. A detailed search was performed in relevant articles published between 2018 and 2023 listed in PubMed, UpToDate, Google Scholar, and ResearchGate, supplemented with manual research. The following keywords were searched in the databases in all possible combinations: Nintedanib; Pirfenidone, interstitial lung disease, and idiopathic pulmonary fibrosis. The most widely accepted method for evaluating the progression of ILD is through the decline in forced vital capacity (FVC), as determined by respiratory function tests. Specifically, a decrease in FVC over a 6-12-month period correlates directly with increased mortality rates. Antifibrotic drugs Pirfenidone and Nintedanib have been extensively validated; however, some patients reported several side effects, predominantly gastrointestinal symptoms (such as diarrhea, dyspepsia, and vomiting), as well as photosensitivity and skin rashes, particularly associated with Pirfenidone. In cases where the side effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. However, further research is needed to optimize the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. Finally, other studies are requested to establish the treatments that can stop ILD progression.
PubMed: 38931376
DOI: 10.3390/ph17060709 -
Journal of Clinical Medicine Jun 2024Neck pain is a pathology with a high impact in terms of physical disability in modern society. The position of the head is related to neck pain. The Frankfort plane...
Neck pain is a pathology with a high impact in terms of physical disability in modern society. The position of the head is related to neck pain. The Frankfort plane determines the position of the skull in space. The profile photograph of the subjects was used to determine the Frankfort plane and to study its degree of inclination. Myofascial pain syndrome is one of the most common causes of musculoskeletal pain. Trigger points are hyperirritable spots located in a palpable taut band of skeletal muscle that is painful on compression or stretch and causes a local twitch in response to snapping or palpation of the band. The aim of this study was to analyze the relationship between the Frankfort plane and the presence of myofascial trigger points causing cervical myofascial pain. : This is a cross-sectional descriptive observational study. All subjects underwent a photographic study to determine the degree of Frankfort plane inclination, and the posterior cervical musculature was palpated to find myofascial trigger points that were measured with a pressure algometer in three cervical locations on the right and left sides. Our study included 47 subjects who had suffered at least one episode of cervical pain in their lifetimes. The mean age was 22.3 ± 2.9 years. Statistically significant results were found in the first right location and sports practice ( = 0.007), in the second right location and gender ( = 0.0097), in the second right location and sports practice ( = 0.0486), in the third right location and gender ( = 0.0098), and in the first, second, and third left locations and gender ( = 0.0083; = 0.024; = 0.0016, respectively). In the correlation between the Frankfort plane and the presence of myofascial trigger points, all locations were positive, with the first right location being statistically significant ( = 0.048). A positive relationship was found between the Frankfort plane and the presence of myofascial trigger points. The greater the angle of the Frankfort plane, the less the myofascial pain.
PubMed: 38930143
DOI: 10.3390/jcm13123614