Tag: pubmed

J Am Chem Soc. 2024 Dec 17. doi: 10.1021/jacs.4c12607. Online ahead of print.

ABSTRACT

NMR is a central tool in the field of metabolomics, thanks to its ability to provide valuable structural and quantitative information with high precision. Most NMR-based metabolomics studies rely on 1D ¹H detection, which is heavily limited by strong peak overlap. ¹³C NMR benefits from a wider spectral dispersion and narrower signal line width but is barely used in metabolomics due to its low sensitivity. Dissolution dynamic nuclear polarization (d-DNP) offers an opportunity to improve ¹³C NMR sensitivity by several orders of magnitude. Here, we show that this emerging hyperpolarized metabolomics approach can provide meaningful information about clinical samples. Achieving sub-mM limits of detection with ¹³C at natural abundance in urine samples was made possible by a meticulous design of the experimental workflow. The analysis of human urine samples from patients with different stages of chronic kidney disease (CKD) was performed using ¹³C d-DNP NMR and benchmarked to conventional ¹H NMR metabolomics at a high magnetic field to explore the complementarity between the two methods. Multivariate analysis of the d-DNP ¹³C NMR dataset provided a statistical model able to distinguish patients with CKD from control patients. Moreover, ¹³C d-DNP NMR spectra highlighted several biomarkers known to be biologically relevant. Some of them were in agreement with those obtained with conventional ¹H NMR, and the results also highlighted the complementarity of biomarker coverage between hyperpolarized and conventional NMR metabolomics. In particular, ¹³C hyperpolarized NMR allowed the annotation of two biomarkers that could not be detected by ¹H NMR because of peak overlap (i.e., guanine and guanidoacetate).

PMID:39690120 | DOI:10.1021/jacs.4c12607

J Magn Reson Imaging. 2024 Dec 17. doi: 10.1002/jmri.29672. Online ahead of print.

ABSTRACT

BACKGROUND: Deep learning (DL) often requires an image quality metric; however, widely used metrics are not designed for medical images.

PURPOSE: To develop an image quality metric that is specific to MRI using radiologists image rankings and DL models.

STUDY TYPE: Retrospective.

POPULATION: A total of 19,344 rankings on 2916 unique image pairs from the NYU fastMRI Initiative neuro database was used for the neural network-based image quality metrics training with an 80%/20% training/validation split and fivefold cross-validation.

FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T T1, T1 postcontrast, T2, and FLuid Attenuated Inversion Recovery (FLAIR).

ASSESSMENT: Synthetically corrupted image pairs were ranked by radiologists (N = 7), with a subset also scoring images using a Likert scale (N = 2). DL models were trained to match rankings using two architectures (EfficientNet and IQ-Net) with and without reference image subtraction and compared to ranking based on mean squared error (MSE) and structural similarity (SSIM). Image quality assessing DL models were evaluated as alternatives to MSE and SSIM as optimization targets for DL denoising and reconstruction.

STATISTICAL TESTS: Radiologists’ agreement was assessed by a percentage metric and quadratic weighted Cohen’s kappa. Ranking accuracies were compared using repeated measurements analysis of variance. Reconstruction models trained with IQ-Net score, MSE and SSIM were compared by paired t test. P < 0.05 was considered significant.

RESULTS: Compared to direct Likert scoring, ranking produced a higher level of agreement between radiologists (70.4% vs. 25%). Image ranking was subjective with a high level of intraobserver agreement ( $94.9\%\pm 2.4\%$ ) and lower interobserver agreement ( $61.47\%\pm 5.51\%$ ). IQ-Net and EfficientNet accurately predicted rankings with a reference image ( $75.2\%\pm 1.3\%$ and $79.2\%\pm 1.7\%$ ). However, EfficientNet resulted in images with artifacts and high MSE when used in denoising tasks while IQ-Net optimized networks performed well for both denoising and reconstruction tasks.

DATA CONCLUSION: Image quality networks can be trained from image ranking and used to optimize DL tasks.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

PMID:39690114 | DOI:10.1002/jmri.29672

Bull Cancer. 2024 Dec 16:S0007-4551(24)00461-2. doi: 10.1016/j.bulcan.2024.11.005. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to explore the mechanism by which HIV infection promotes cervical cancer and precancerous lesions.

METHODS: This was a retrospective observational study including 96 patients with high-risk HPV-16 infection who underwent cervical biopsy, cervical conization, or hysterectomy. Among them, 43 patients were diagnosed with both HIV and cervical cancer or precancerous lesions. High-risk HPV infection (HPV16+) positive samples were collected, and total RNA was extracted and amplified by fluorescence quantitative PCR. The expression of HPV E2 and E6 in cervical tissues of HIV-infected and non-HIV-infected patients with high-risk HPV was determined.

RESULTS: As the degree of cervical tissue lesions increased, the proportions of integrated HPV-16 increased significantly within both HIV-negative (P=0.008) and HIV-positive groups (P=0.027). In comparison to the HIV-positive group, although the HIV-negative group had a higher proportion of free type HPV-16 infection (64.3% vs. 35.7%) and a lower proportion of integrated type infection (41.7% vs. 58.3%), the differences were not statistically significant (P=0.117). The lower the CD4+ T lymphocyte level, the greater the possibility of HPV-16 integrated infection.

CONCLUSIONS: Patients with HIV and HPV-16 infection exhibit a significantly higher rate of integrated HPV-16 infection, which is closely linked to HIV-induced immunosuppression, particularly the depletion of CD4+ T lymphocytes. This integration accelerates the progression of cervical lesions, increasing the risk of developing high-grade cervical intraepithelial neoplasia or cervical cancer. These findings underscore the need for targeted screening and therapeutic strategies in HIV-positive women to prevent HPV-related malignancies.

PMID:39690095 | DOI:10.1016/j.bulcan.2024.11.005

Nutr Metab Cardiovasc Dis. 2024 Nov 9:103789. doi: 10.1016/j.numecd.2024.103789. Online ahead of print.

ABSTRACT

AIMS: Atherosclerosis is a life-threatening disease that develops when a plaque builds up inside an artery and progresses silently. Identifying the early pathological changes and the biomarkers of atherosclerosis deserves attention. We aimed to systematically study and integrate the various metabolites of atherosclerosis in the level of disease to provide more evidences to support early prevention and treatment of atherosclerosis.

DATA SYNTHESIS: The protocol was registered with PROPSERO (CRD42023441845). We searched 14,985 records via EMBASE, PubMed, Web of Science, WanFang data, VIP data, and CNKI databases. The collected metabolites were for qualitative and quantitative meta-analysis. The I² statistic estimated heterogeneity, with over 50 % considered to adopt the random-effects model. A total of 49 articles were included in the meta-analysis. We finally integrated 83 and 16 metabolites presented more than two times in inclusion studies, respectively in blood (plasma and serum) and urine. Among them, the level of citric acid (SMD = -10.35 [95%CI -15.03, -5.67], p < 0.001), lactic acid (SMD = 6.32 [95%CI 0.12, 12.52], p < 0.001) and TMAO (SMD = 1.40 [95%CI 0.27, 2.53], p < 0.001) had significant differences between atherosclerosis and controls. And we observed blood stasis syndrome of atherosclerosis patients present arterial ischemia and energy disorder obviously.

CONCLUSIONS: The study provides an in-depth understanding of the roles of metabolites on atherosclerosis progression and prediction primarily in Chinese population, which contributing to development of prevention and therapeutic potential in the future.

PMID:39690044 | DOI:10.1016/j.numecd.2024.103789

Jt Comm J Qual Patient Saf. 2024 Nov 2:S1553-7250(24)00330-1. doi: 10.1016/j.jcjq.2024.10.012. Online ahead of print.

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic affected quality improvement work that was key to hospital-acquired infection (HAI) prevention efforts for many hospitals. Central line-associated bloodstream infection (CLABSI) standardized infection ratios (SIRs) were highly affected by the pandemic.

METHODS: After seeing an increase in CLABSI SIRs through early 2021, a health care system including 12 acute care hospitals in the midwestern United States focused on processes and process measures for CLABSI prevention. Each hospital was asked to identify a medical provider, nursing, and infection prevention lead to champion the work (identified as a CLABSI triad). CLABSI triads emphasized best practice expectations, standardized technology and products, and implemented reporting and trending of compliance. Work started in July 2021, with multiple initiatives rolled out through the end of 2022. CLABSI SIRs and standardized utilization ratios (SURs) were analyzed with interrupted time series analysis; changes in several process measures were analyzed using Wilcoxon rank sum exact testing.

RESULTS: A 47.5% decrease was seen in CLABSI SIR through the study period, with SIR = 0.61 from 2023 to April 2024. The slope of the trend line for CLABSI SIR and central line utilization had a significant downward trend in the intervention time frame (p = 0.04 and p < 0.01, respectively). CLABSI prevention best practices improved statistically during the study period.

CONCLUSION: Intense focus by leadership on key CLABSI prevention process measures was associated with lower CLABSI SIRs.

PMID:39690035 | DOI:10.1016/j.jcjq.2024.10.012

Clin Ther. 2024 Dec 16:S0149-2918(24)00371-0. doi: 10.1016/j.clinthera.2024.11.023. Online ahead of print.

ABSTRACT

PURPOSE: Down syndrome regression disorder (DSRD) is a rare neuropsychiatric condition affecting otherwise healthy individuals with Down syndrome. Multiple studies on DSRD have revealed that immunotherapy with intravenous immunoglobulin (IVIg) is both safe and effective, although site of infusion has never been studied. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD receiving home-based infusions.

METHODS: A single-center, retrospective chart review evaluating infusion reactions was performed for individuals meeting criteria for DSRD and having received IVIg infusions between 2019 and 2024. Adverse events (AEs) were evaluated for severity and need for alterations in infusion plan. A cohort of individuals receiving home-based infusions was compared with a cohort of individuals receiving infusions at an academic medical center.

FINDINGS: A total of 315 individuals (162 institutional infusions [51%] and 153 home infusions [49%]) met the inclusion criteria. There were no statistical differences between the demographic and clinical features of the cohorts. Individuals receiving home infusions had the same rate of AE during an infusion (P = 0.14), although they did have a lower number of total AEs (P < 0.001). Individuals receiving home infusions experienced a lower number of behavioral issues with infusions (P = 0.03) and had significantly lower discontinuations of infusions secondary to behavioral issues (P = 0.04).

IMPLICATIONS: Rates of AEs and serious AEs in those with DSRD were the same regardless of site of infusion. These data should be considered in policy regarding the appropriateness of home-based infusions as a safe alternative, when suitable for patients and caregivers, for individuals with DSRD.

PMID:39690018 | DOI:10.1016/j.clinthera.2024.11.023

Surgery. 2024 Dec 16:108937. doi: 10.1016/j.surg.2024.09.050. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic lymphocytic thyroiditis is an autoimmune thyroid disorder and the most common cause of hypothyroidism in women. Many studies suggest that chronic lymphocytic thyroiditis contributes to a diagnostic challenge in thyroid nodules and may increase the risk of developing papillary thyroid cancer. This study examines preoperative clinical factors and tumor characteristics associated with papillary thyroid cancer among patients with chronic lymphocytic thyroiditis.

METHODS: A retrospective review of prospectively collected data of patients who underwent total thyroidectomy between 2009 and 2020 at a tertiary institution was performed. Sociodemographic factors, comorbidities, surgeon-performed ultrasound, fine needle aspiration, tumor characteristics, and final histopathology were studied. Patients were subdivided into 2 groups based on final histopathology: chronic lymphocytic thyroiditis alone and chronic lymphocytic thyroiditis with papillary thyroid cancer. χ² tests were used for independence among categorical variables, and comparisons were based on t tests.

RESULTS: Of 2,200 total thyroidectomy patients, the majority of 250 patients with chronic lymphocytic thyroiditis were women (90.4%) and had a mean age of 50 (±13) years. All patients with chronic lymphocytic thyroiditis underwent preoperative ultrasound, 89.2% (n = 223) underwent fine needle aspiration preoperatively, and 25.2% (n = 63) presented with obstructive symptoms, whereas 53.6% (n = 134) had papillary thyroid cancer on final histopathology and 74.8% (n = 187) underwent central neck lymph node removal. When comparing patients with chronic lymphocytic thyroiditis alone with those with chronic lymphocytic thyroiditis and papillary thyroid cancer, no differences for sex, race, nodule density, nodule size, echogenicity, irregular borders, and number of nodules were identified, but there was a statistically significant difference for obstructive symptoms (37.1% vs 14.9%), multinodular goiter (55.8% vs 32.3%), microcalcifications (18.4% vs 36.6%), Bethesda III fine needle aspiration results (41.4% vs 27.4%), and central neck lymph node removal (58.6% vs 88.8%), respectively (P < .05). Preoperative fine needle aspiration in patients with chronic lymphocytic thyroiditis for papillary thyroid cancer had a positive predictive value of 92.9%, negative predictive value of 83.3%, false positive rate of 13.8%, and false negative rate of 8.8%.

CONCLUSION: Although thyroid ultrasound features may have limited utility for malignancy, fine needle aspiration of index thyroid nodules still demonstrates a high positive predictive value in stratifying patients with chronic lymphocytic thyroiditis with papillary thyroid cancer. A higher level of suspicion preoperatively may be needed to avoid unnecessary lymph node removal for patients with chronic lymphocytic thyroiditis.

PMID:39690015 | DOI:10.1016/j.surg.2024.09.050

Aust Crit Care. 2024 Dec 16:101147. doi: 10.1016/j.aucc.2024.101147. Online ahead of print.

ABSTRACT

BACKGROUND: The provision of end-of-life care (EOLC) is an ongoing component of practice in intensive care units (ICUs). Interdisciplinary, multicomponent interventions may enhance the quality of EOLC for patients and the experience of family members and ICU clinicians during this period.

OBJECTIVES: This study aimed to assess the impact of a multicomponent intervention on EOLC practices in the ICU and family members’ and clinicians’ perceptions of EOLC.

METHODS: A before-and-after interventional study design was used. Interventions comprising of EOLC guidelines, environmental and memory-making resources, EOLC education day for nurses, web-based resources, and changes to EOLC documentation processes were implemented in a 30-bed adult tertiary ICU from September 2020 onwards. Data collection included electronic health record audits of care provided post initiation of EOLC and family and clinician surveys. Open-ended survey questions were analysed using content analysis. Data from before and after the intervention were compared using the Chi-squared test for categorical variables, unpaired two-sample t-tests for normally distributed continuous measurements, and Mann-Whitney U tests for non-normally distributed data.

FINDINGS: A reduction in documented observations and medications and an increased removal of invasive devices unrelated to EOLC were observed post the intervention. The mean overall satisfaction of family members improved from 4.5 to 5 (out of 5); however, this was not statistically significant. Statistically significant improvements in clinicians’ perception of overall quality of EOLC (mean difference = 0.28, 95% confidence interval: 0.18, 0.37; t₂₈₂ = 5.8, P < 0.01) were found. Although statistically significant improvements were evident in all subscales measured, clinicians’ work stress related to EOLC and support for staff, patients, and their families were identified as needing further improvement.

CONCLUSIONS: The development and implementation of a multicomponent interdisciplinary intervention successfully improved EOLC quality, as measured by chart audit and family and clinician perceptions. Continuing interdisciplinary collaboration is needed to drive further change to continue to support high-quality EOLC for patients, families, and clinicians in the ICU.

PMID:39689996 | DOI:10.1016/j.aucc.2024.101147

Semin Thromb Hemost. 2024 Dec 17. doi: 10.1055/s-0044-1800980. Online ahead of print.

ABSTRACT

An increasing number of Mendelian randomization (MR) studies have evaluated the causal link between smoking and venous thromboembolism (VTE). However, previous studies often rely on single genetic variants related to smoking quantity and exhibit various other shortcomings, making them prone to pleiotropy and potentially leading to imprecise causal estimates. Thus, the deeper causal mechanisms remain largely unexplored. This MR study reassessed the causal relationship between smoking and VTE, including its subtypes-deep vein thrombosis (DVT) and pulmonary embolism (PE). Data on VTE were sourced from the FinnGen consortium with nonoverlapping sample sizes. The smoking phenotypes analyzed included smoking initiation, lifetime smoking, the number of cigarettes smoked per day by both current and former smokers (CigDay), and total pack-years of smoking in adulthood. The primary analytical method was inverse-variance-weighted (IVW), supplemented by multiple verification methods to ensure robust results. Statistical rigor was ensured through LDtrait pruning and Steiger filtering for reverse causation, with comprehensive sensitivity analyses including RadialMR confirming the findings’ robustness. After Bonferroni correction, this study demonstrates significant causal evidence linking lifetime smoking with the incidence of VTE (odds ratio [OR]_IVW = 1.50, 95% confidence interval [CI] 1.21-1.85, p = 1.75 × 10^-4) and PE (OR_IVW = 1.69, 95% CI 1.25-2.28, p = 6.55 × 10^-4), and suggestive evidence with DVT, consistent in direction with previous studies but showing considerable differences in effect sizes and significance. Additionally, CigDay (past and current) increases the risks of VTE and DVT, while no causal link was found between smoking initiation and VTE or its subtypes (p < 0.05), both directly contradicting previous conclusions. Furthermore, our study is the first to suggest a causal link between pack-years and an increased risk of VTE. This MR study employed rigorous statistical pruning of its instrumental variables, using the most comprehensive smoking phenotype to date. It successfully mitigated biases such as winner’s curse, yielding causal effect results distinct from previous studies.

PMID:39689867 | DOI:10.1055/s-0044-1800980

Angle Orthod. 2025 Jan 1;95(1):35-42. doi: 10.2319/050224-349.1.

ABSTRACT

OBJECTIVES: To compare the biomechanics of labial and lingual fixed orthodontic treatment options for a simulated curve of Spee malocclusion.

MATERIALS AND METHODS: An in vitro electromechanical orthodontic simulator was used to measure the three-dimensional forces and moments on each tooth of a mandibular arch. Labial and lingual brackets, both with 0.018-inch slot sizes, were bonded to mechanical teeth. Three archwire forms were considered: labial straight, lingual straight, and lingual mushroom. The simulator was set in a passive levelled position with 0.016-inch × 0.022-inch stainless steel archwires, then teeth were moved to a curve of Spee maloclussion with the first premolar intruded 1.5 mm and the canine and second premolar intruded 0.75 mm. Two-way mixed multivariate analysis of variance (α = 0.05) was used to compare forces and moments generated among the three archwires.

RESULTS: Statistical differences were found in 55 of 63 comparisons of forces and moments between archwire types for each tooth around the arch. The lowest force magnitudes were measured for labial straight archwires at each tooth position. The lateral incisor experienced the largest gingival forces with all archwire forms. The first premolar and first molar experienced labial-lingual crown tipping moments in opposite directions between labial and the two lingual archwire forms.

CONCLUSIONS: Biomechanical differences between labial, lingual straight, and lingual mushroom treatment modalities for the correction of curve of Spee misalignments were elucidated. Labial straight archwire exerted the lowest force magnitudes overall. For both lingual archwire forms, the labial-lingual inclination of the first premolar could be highly variable during levelling.

PMID:39689862 | DOI:10.2319/050224-349.1