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Frontiers in Aging Neuroscience 2024Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday...
Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.
BACKGROUND
Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults.
METHODS
Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education.
RESULTS
Amyloid [unstandardized partial regression coefficient estimate (β) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [β = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time.
CONCLUSION
Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.
PubMed: 38934017
DOI: 10.3389/fnagi.2024.1420290 -
Frontiers in Endocrinology 2024Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC)...
OBJECTIVE
Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC) required to achieve proficiency are still lacking.
MATERIALS AND METHODS
The first 179 RFA procedures performed by a single operator in patients with non-functioning BTN were retrospectively analyzed. Six-month nodule volume reduction rate (VRR) ≥ 50% was regarded as reflection of proficiency. Multiple linear regression analysis has been performed to determine the relationship between the VRR and clinical variables. Cumulative sum (CUSUM) charts were plotted to assess LCs for all consecutive procedures and in relation to basal nodule size. In details, Group 1 (G1): 57 patients with small nodules (<10 ml); Group 2 (G2): 87 patients with intermediate nodules (10 - 25 ml); Group 3 (G3): 35 patients with large size (> 25 ml).
RESULTS
LC of all 179 procedures showed 3 phases: initial learning (1-39 procedures); consolidation (40-145 procedures); and experienced period (146-179 procedures). For G1 and G2 proficiency is achieved starting from the 10th procedure within the group (or 37th considering consecutively all procedures) and from the 59th procedure within the group (or 116th considering consecutively all procedures), respectively. LC of G3 did not detect operator proficiency.
CONCLUSION
Specific LCs exist concerning the basal size of the nodule treated with RFA. In nodules with baseline volume > 25 ml suboptimal VRR has to be expected. Previously achieved experience on small-intermediate nodules does not seem to provide advantages in terms of higher VRR in the treatment of large nodules. Other potential and non-modifiable factors likely play a key role in the final volume reduction independently from the increased skill of the operator.
Topics: Humans; Thyroid Nodule; Female; Male; Radiofrequency Ablation; Retrospective Studies; Middle Aged; Adult; Learning Curve; Clinical Competence; Aged; Treatment Outcome
PubMed: 38933827
DOI: 10.3389/fendo.2024.1399912 -
Frontiers in Endocrinology 2024The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective...
OBJECTIVES
The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI).
METHODS
Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter.
RESULTS
The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I treatment.
CONCLUSION
This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Lung Neoplasms; Female; Male; Middle Aged; Adult; Aged; Deep Learning; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Cohort Studies
PubMed: 38933823
DOI: 10.3389/fendo.2024.1429115 -
Frontiers in Oncology 2024Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human...
INTRODUCTION
Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR).
PATIENTS AND METHODS
Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model.
RESULTS
Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925).
CONCLUSION
In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.
PubMed: 38933451
DOI: 10.3389/fonc.2024.1377842 -
European Heart Journal Open May 2024Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and...
AIMS
Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.
METHODS AND RESULTS
To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.
CONCLUSION
These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.
PubMed: 38933427
DOI: 10.1093/ehjopen/oeae043 -
Frontiers in Immunology 2024To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC)...
OBJECTIVES
To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image.
METHODS
This retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV).
RESULTS
In the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686.
CONCLUSION
The quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Male; Female; Neoadjuvant Therapy; Middle Aged; Retrospective Studies; Aged; Tomography, X-Ray Computed; Treatment Outcome; Machine Learning; Immunotherapy; Adult; Pathologic Complete Response
PubMed: 38933281
DOI: 10.3389/fimmu.2024.1414954 -
Frontiers in Immunology 2024Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches...
OBJECTIVE
Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches are mostly clinical trials and have reached various conclusions. Our objective is to investigate the efficacy of PD-1 inhibitor-based treatment as first-line therapy for MGC, utilizing real-world data from China, and further analyze predictive biomarkers for efficacy.
METHODS
This retrospective study comprised 105 patients diagnosed with MGC who underwent various PD-1 inhibitor-based treatments as first-line therapy at West China Hospital of Sichuan University from January 2018 to December 2022. Patient characteristics, treatment regimens, and tumor responses were extracted. We also conducted univariate and multivariate analyses to assess the relationship between clinical features and treatment outcomes. Additionally, we evaluated the predictive efficacy of several commonly used biomarkers for PD-1 inhibitor treatments.
RESULTS
Overall, after 28.0 months of follow-up among the 105 patients included in our study, the objective response rate (ORR) was 30.5%, and the disease control rate (DCR) was 89.5% post-treatment, with two individuals (1.9%) achieving complete response (CR). The median progression-free survival (mPFS) was 9.0 months, and the median overall survival (mOS) was 22.0 months. According to both univariate and multivariate analyses, favorable OS was associated with patients having Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. Additionally, normal baseline levels of carcinoembryonic antigen (CEA), as well as the combination of PD-1 inhibitors with chemotherapy and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive MGC, independently predicted longer PFS and OS. However, microsatellite instability/mismatch repair (MSI/MMR) status and Epstein-Barr virus (EBV) infection status were not significantly correlated with PFS or OS extension.
CONCLUSION
As the first-line treatment, PD-1 inhibitors, either as monotherapy or in combination therapy, are promising to prolong survival for patients with metastatic gastric cancer. Additionally, baseline level of CEA is a potential predictive biomarker for identifying patients mostly responsive to PD-1 inhibitors.
Topics: Humans; Stomach Neoplasms; Male; Female; Retrospective Studies; Middle Aged; Aged; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Adult; China; Biomarkers, Tumor; Treatment Outcome; Neoplasm Metastasis; Antineoplastic Combined Chemotherapy Protocols; East Asian People
PubMed: 38933261
DOI: 10.3389/fimmu.2024.1370860 -
Frontiers in Public Health 2024Uncertainty and inconsistency in terminology regarding the risk factors (RFs) for in-hospital falls are present in the literature. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uncertainty and inconsistency in terminology regarding the risk factors (RFs) for in-hospital falls are present in the literature.
OBJECTIVE
(1) To perform a literature review to identify the fall RFs among hospitalized adults; (2) to link the found RFs to the corresponding categories of international health classifications to reduce the heterogeneity of their definitions; (3) to perform a meta-analysis on the risk categories to identify the significant RFs; (4) to refine the final list of significant categories to avoid redundancies.
METHODS
Four databases were investigated. We included observational studies assessing patients who had experienced in-hospital falls. Two independent reviewers performed the inclusion and extrapolation process and evaluated the methodological quality of the included studies. RFs were grouped into categories according to three health classifications (ICF, ICD-10, and ATC). Meta-analyses were performed to obtain an overall pooled odds ratio for each RF. Finally, protective RFs or redundant RFs across different classifications were excluded.
RESULTS
Thirty-six articles were included in the meta-analysis. One thousand one hundred and eleven RFs were identified; 616 were linked to ICF classification, 450 to ICD-10, and 260 to ATC. The meta-analyses and subsequent refinement of the categories yielded 53 significant RFs. Overall, the initial number of RFs was reduced by about 21 times.
CONCLUSION
We identified 53 significant RF categories for in-hospital falls. These results provide proof of concept of the feasibility and validity of the proposed methodology. The list of significant RFs can be used as a template to build more accurate measurement instruments to predict in-hospital falls.
Topics: Accidental Falls; Humans; Risk Factors; Proof of Concept Study; Hospitalization
PubMed: 38932769
DOI: 10.3389/fpubh.2024.1390185 -
Vaccines May 2024Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and...
Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids.
PubMed: 38932291
DOI: 10.3390/vaccines12060562 -
Viruses Jun 2024Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in...
Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in Victoria, Australia, who inject drugs or are living with hepatitis C, to identify missed opportunities for hepatitis C care. Adult hospital inpatients and emergency department (ED) attendees from 2018 to 2021 with indications for intravenous drug use (IDU) or hepatitis C on their discharge or ED summary were included. Data sources: hospital admissions, pathology, hospital pharmacy, and outpatients. We assessed progression through the testing cascade and performed logistic regression analysis for predictors of hepatitis C care, including testing and treatment. Of 79,923 adults admitted, 1345 (1.7%) had IDU-coded separations and 628 (0.8%) had hepatitis C-coded separations (N = 1892). Hepatitis C virus (HCV) status at the end of the study was unknown for 1569 (82.9%). ED admissions were associated with increased odds of not providing hepatitis C care (odds ratio 3.29, 95% confidence interval 2.42-4.48). More than 2% of inpatients at our hospital have an indication for testing, however, most are not being tested despite their hospital contact. As we work toward HCV elimination in our region, we need to incorporate testing and linkage strategies within hospital departments with a higher prevalence of people at risk of infection.
Topics: Humans; Retrospective Studies; Male; Hepatitis C; Female; Middle Aged; Adult; Inpatients; Hepacivirus; Substance Abuse, Intravenous; Hospitalization; Victoria; Aged; Emergency Service, Hospital; Mass Screening; Young Adult
PubMed: 38932269
DOI: 10.3390/v16060979