Tag: pubmed

J Orthop Surg Res. 2023 Oct 4;18(1):750. doi: 10.1186/s13018-023-04235-0.

ABSTRACT

BACKGROUND: Osteonecrosis of the femoral head is a degenerative condition linked to corticosteroids, alcoholism, or trauma. With its rising prevalence due to increased hormone drug use and its debilitating effects on young to middle-aged individuals, understanding its association with specific laboratory indicators can aid early diagnosis and prevention.

METHODS: Upon retrospective analysis of the clinical data pertaining to individuals diagnosed with femoral head necrosis, spanning from January 2016 to January 2022, a comprehensive evaluation was conducted within the same time frame. The study aimed to ascertain the presence of femoral head necrosis in a total of 1176 individuals. A total of 1036 healthy patients were recruited randomly, ensuring that their ages matched. The risk variables associated with the utilization of logistic regression analysis and analysis techniques are employed. The patient examines the age distribution within a specific age group.

RESULTS: The levels of high-density lipoprotein, low-density lipoprotein A1, lipoprotein B1, total protein, albumin, globulin, and other lipophilic metabolism and coagulation markers exhibited a statistically significant increase compared to the control group. A multifactor logistic regression analysis was conducted to identify potential risk factors associated with femoral head necrosis in patients.

CONCLUSION: Femoral head necrosis is associated with a range of variables including coagulation malfunction, lipid metabolic abnormalities, and inflammation.

PMID:37794495 | DOI:10.1186/s13018-023-04235-0

Genome Med. 2023 Oct 4;15(1):79. doi: 10.1186/s13073-023-01233-z.

ABSTRACT

BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.

METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.

RESULTS: Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.

CONCLUSIONS: These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.

PMID:37794492 | DOI:10.1186/s13073-023-01233-z

EBioMedicine. 2023 Oct 2;97:104823. doi: 10.1016/j.ebiom.2023.104823. Online ahead of print.

ABSTRACT

BACKGROUND: Excessive use of blood cultures (BCs) in Emergency Departments (EDs) results in low yields and high contamination rates, associated with increased antibiotic use and unnecessary diagnostics. Our team previously developed and validated a machine learning model to predict BC outcomes and enhance diagnostic stewardship. While the model showed promising initial results, concerns over performance drift due to evolving patient demographics, clinical practices, and outcome rates warrant continual monitoring and evaluation of such models.

METHODS: A real-time evaluation of the model’s performance was conducted between October 2021 and September 2022. The model was integrated into Amsterdam UMC’s Electronic Health Record system, predicting BC outcomes for all adult patients with BC draws in real time. The model’s performance was assessed monthly using metrics including the Area Under the Curve (AUC), Area Under the Precision-Recall Curve (AUPRC), and Brier scores. Statistical Process Control (SPC) charts were used to monitor variation over time.

FINDINGS: Across 3.035 unique adult patient visits, the model achieved an average AUC of 0.78, AUPRC of 0.41, and a Brier score of 0.10 for predicting the outcome of BCs drawn in the ED. While specific population characteristics changed over time, no statistical points outside the statistical control range were detected in the AUC, AUPRC, and Brier scores, indicating stable model performance. The average BC positivity rate during the study period was 13.4%.

INTERPRETATION: Despite significant changes in clinical practice, our BC stewardship tool exhibited stable performance, suggesting its robustness to changing environments. Using SPC charts for various metrics enables simple and effective monitoring of potential performance drift. The assessment of the variation of outcome rates and population changes may guide the specific interventions, such as intercept correction or recalibration, that may be needed to maintain a stable model performance over time. This study suggested no need to recalibrate or correct our BC stewardship tool.

FUNDING: No funding to disclose.

PMID:37793210 | DOI:10.1016/j.ebiom.2023.104823

Tissue Cell. 2023 Sep 27;85:102226. doi: 10.1016/j.tice.2023.102226. Online ahead of print.

ABSTRACT

This study aimed to investigate the protective effect of melatonin against the acute toxicity of cisplatin in ocular tissues. The eyes of 40 rats were divided into 4 groups: Control group (10 rats), Melatonin (Mel) group (10 rats), Cisplatin (Cis) group (10 rats), Melatonin (Mel) + Cisplatin (Cis) group (10 rats). Retina, cornea, and ciliary body tissues were examined after hematoxylin-eosin staining of sections obtained from the eyes and were scored for disorganization and degeneration. Apoptotic cells were counted for the retina, cornea, and ciliary body with the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) method. The total antioxidant status (TAS) / total oxidant status (TOS) of homogenized eye tissues were measured. While apoptotic cells were found to increase in the cornea of the Cisplatin (Cis) group, no difference was found regarding the retina and ciliary body cell count. An increased number of apoptotic cells in the cornea of the Cis group was found while there was a decrease in the group where Cisplatin and Melatonin were administered together (Mel+Cis group). There was no statistically significant difference amongst groups for TOS or TAS. Melatonin had a partial protective effect against histological damage.

PMID:37793209 | DOI:10.1016/j.tice.2023.102226

Clin Exp Dermatol. 2023 Oct 4:llad319. doi: 10.1093/ced/llad319. Online ahead of print.

ABSTRACT

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG), and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described.

OBJECTIVE: Characterization of serum reactivities in DH.

METHODS: This multicenter international study analyzed sera from 242 DH patients taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analyzed by indirect immunofluorescence (IF) on monkey esophagus, and by enzyme-linked immune sorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG, and deamidated gliadin (GAF3X).

RESULTS: IgA indirect IF microscopy on monkey esophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, 99.0%), IgA TG3/eTG ELISA (72.7%, 95.0%), and IgA GAF3X ELISA (69.0%, 98.5%).

CONCLUSION: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG, and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey esophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 3.5% when combined with IgA TG2/tTG ELISA.

PMID:37793183 | DOI:10.1093/ced/llad319

J Clin Endocrinol Metab. 2023 Oct 4:dgad584. doi: 10.1210/clinem/dgad584. Online ahead of print.

ABSTRACT

CONTEXT: Volatile organic compounds (VOCs) are pervasive environmental pollutants that have been linked to various adverse health effects. However, the impact of ambient VOCs, whether individually or in mixtures, on diabetes remains uncertain and requires further investigation.

OBJECTIVE: This study investigates the effects of ambient VOCs exposure, whether single or mixed, on diabetes mellitus and glucose homeostasis in the general population.

METHODS: Urinary concentrations of VOCs metabolites were obtained from National Health and Nutrition Examination Survey. Survey-weighted logistic regression and generalized linear regression were used to explore the associations between individual VOC exposure and diabetes risk and glucose homeostasis indicators, respectively. Weighted quantile sum (WQS) regression models were applied to assess the combined effects of VOCs mixtures.

RESULTS: Out of 8468 participants, 1504 had diabetes mellitus. Eight VOCs metabolites showed positive associations with diabetes mellitus (OR ranged from 1.15 to 1.43, all P<0.05), insulin resistance (OR ranged from 1.02 to 1.06, P＜0.05), and other glucose homeostasis indicators (β ranged from 0.04 to 2.32, all P<0.05). Mixed-VOCs models revealed positive correlations between the WQS indices and diabetes risk (OR=1.52, 95% CI: 1.29-1.81), insulin resistance (OR=1.36, 95% CI=1.14-1.62), and other glucose homeostasis indicators (β ranged from 0.17 to 2.22, all P<0.05).

CONCLUSION: Urinary metabolites of ambient VOCs are significantly associated with an increased diabetes risk and impaired glucose homeostasis. Thus, primary prevention policies aimed at reducing ambient VOCs could attenuate diabetes burden.

PMID:37793167 | DOI:10.1210/clinem/dgad584

Oral Dis. 2023 Oct 4. doi: 10.1111/odi.14754. Online ahead of print.

ABSTRACT

OBJECTIVE: Opiorphin is a pentapeptide secreted in saliva and has a strong analgesic effect. Salivary opiorphin has been shown to increase in orofacial pain and may act as a pain reliever in pain caused by denture-related ulcers. The current study aimed to evaluate the salivary opiorphin levels in traumatic ulcers caused by ill-fitting dentures and demonstrate whether there is any correlation between trauma-related pain levels and salivary opiorphin levels.

MATERIALS AND METHODS: Twenty-two individuals with new full dentures and a complaint of pain due to ill-fitting were included in this study. Patients were asked to rate their level of pain on a visual analog scale (VAS). Then, saliva specimens were collected at the first visit with the complaint of pain and 7 days following the denture adjustment.

RESULTS: The average saliva opiorphin level before and after denture adjustment were 19.29 ± 5.44 and 15.78 ± 3.95 ng/mL, respectively. A dependent (paired) t-test determined that the mean salivary opiorphin level differed statistically significantly before and after the adjustment of the dentures.

CONCLUSIONS: The findings show that salivary opiorphin levels increase in pain associated with denture-related traumatic ulcers. Adjusting the dentures resulted in pain relief and a statistically significant reduction in opiorphin levels.

PMID:37793134 | DOI:10.1111/odi.14754

Neuro Oncol. 2023 Oct 4;25(Supplement_4):iv1-iv99. doi: 10.1093/neuonc/noad149.

ABSTRACT

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.

PMID:37793125 | DOI:10.1093/neuonc/noad149

Epidemiology. 2023 Oct 2. doi: 10.1097/EDE.0000000000001680. Online ahead of print.

ABSTRACT

BACKGROUND: To meet regulatory approval, interventions must demonstrate efficacy against a primary outcome in randomized clinical trials. However, when there are multiple clinically relevant outcomes, selecting a single primary outcome is challenging. Incorporating data from multiple outcomes may increase statistical power in clinical trials. We examined methods for analyzing data on multiple endpoints, inspired by real-world trials of interventions against respiratory syncytial virus (RSV).

METHOD: We developed a novel permutation test representing a weighted average of individual outcome test statistics (wavP) to evaluate intervention efficacy in a multiple-endpoint analysis. We compared the power and type I error rate of this approach to the Bonferroni correction (bonfT) and the minP permutation test. We evaluated the different approaches using simulated data from three hypothetical trials varying the intervention efficacy, correlation, and incidence of the outcomes, as well as data from a real-world RSV clinical trial.

RESULTS: When the vaccine efficacy against different outcomes was similar, wavP yielded higher power than bonfT and minP; in some scenarios the improvement in power was substantial. In settings where vaccine efficacy was notably larger against one endpoint compared to the others, all three methods had similar power. We developed an R package, PERMEATE, to guide selection of the most appropriate method for analyzing multiple endpoints in clinical trials.

CONCLUSIONS: Analyzing multiple endpoints using a weighted permutation method can increase power while controlling the type I error rate compared to established methods under conditions mirroring real-world RSV clinical trials.

PMID:37793120 | DOI:10.1097/EDE.0000000000001680

Med Phys. 2023 Oct 4. doi: 10.1002/mp.16774. Online ahead of print.

ABSTRACT

BACKGROUND: Pulsed wave Doppler ultrasound is a useful modality for assessing vascular health as it quantifies blood flow characteristics. To facilitate accurate diagnosis, accuracy and consistency of this modality should be assessed through Doppler quality assurance (QA).

PURPOSE: The purpose of this study was to characterize the accuracy, reproducibility, and inter-scanner variability of ultrasound flow velocity measurements via a flow phantom, with a focus on the effect of systematic acquisition parameters on measured flow velocity accuracy.

METHODS: Using a manufacturer-calibrated flow phantom, pulsed wave measurements were acquired on five clinical systems (iU22, Philips) with three models of transducers, including both linear and curvilinear models. The peak and mean flow velocities were estimated by vendor-supplied spectral analysis tools. To investigate intra- and inter-scanner variability, measurements were repeated using each scanner-transducer pair under a standardized set of conditions. Inter-scanner variability was assessed using ANOVA. Flow velocity accuracy was investigated by mean absolute percentage error. The impacts of receive gain, measurement depth, and beam steering on measured flow velocity accuracy were examined by varying each parameter over its available range and comparing to the ground truth flow velocity.

RESULTS: Inter-scanner variability was statistically significant for peak flow measurements made using both linear and curvilinear transducers, though absolute differences in measured velocity were small. Inter-scanner variability was not statistically significant for mean flow velocity. Receive gain, measurement depth, and beam steering were all found to impact the accuracy of measured flow characteristics for linear transducers. Accuracy of the flow measurements made with the curvilinear transducer demonstrated high consistency to changes in receive gain at a constant depth, though were impacted by increasing the measurement depth.

CONCLUSIONS: Carefully and consistently selected acquisition and set-up parameters are essential in order to establish a reliable and meaningful QA program.

PMID:37793117 | DOI:10.1002/mp.16774