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Ghosal S. Impact of Methodological Assumptions and Covariates on the Cutoff Estimation in ROC Analysis. Biom J 2025; 67:e70053. [PMID: 40289475 PMCID: PMC12035111 DOI: 10.1002/bimj.70053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 10/29/2024] [Accepted: 11/11/2024] [Indexed: 04/30/2025]
Abstract
The receiver operating characteristic (ROC) curve stands as a cornerstone in assessing the efficacy of biomarkers for disease diagnosis. Beyond merely evaluating performance, it provides with an optimal cutoff for biomarker values, crucial for disease categorization. While diverse methodologies exist for cutoff estimation, less attention has been paid to integrating covariate impact into this process. Covariates can strongly impact diagnostic summaries, leading to variations across different covariate levels. Therefore, a tailored covariate-based framework is imperative for outlining covariate-specific optimal cutoffs. Moreover, recent investigations into cutoff estimators have overlooked the influence of ROC curve estimation methodologies. This study endeavors to bridge this gap by addressing the research void. Extensive simulation studies are conducted to scrutinize the performance of ROC curve estimation models in estimating different cutoffs in varying scenarios, encompassing diverse data-generating mechanisms and covariate effects. In addition, leveraging the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set, the research assesses the performance of different biomarkers in diagnosing Alzheimer's disease and determines the suitable optimal cutoffs.
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Affiliation(s)
- Soutik Ghosal
- Division of BiostatisticsDepartment of Public Health SciencesSchool of MedicineUniversity of VirginiaCharlottesvilleVirginiaUSA
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2
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Hardy L, Martin M, Barré C, Tanquerel L. Prevalence of gastric ulcers in horses from the French Republican Guard cavalry regiment and association with plasma gamma-glutamyl transpeptidase activity. J Equine Vet Sci 2025; 149:105566. [PMID: 40204167 DOI: 10.1016/j.jevs.2025.105566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 02/28/2025] [Accepted: 04/06/2025] [Indexed: 04/11/2025]
Abstract
Equine gastric ulceration syndrome (EGUS) is a common condition, affecting both glandular (EGGD) and squamous (ESGD) mucosa of the stomach. It has a high prevalence, particularly in racehorses and sport horses, causing clinical signs from poor performance to colic. Gastroscopy, the reference standard diagnostic method, is expensive, prompting the search for alternative tests. Previous studies noted changes in blood markers, including elevated gamma-glutamyl transpeptidase (GGT) activity in ulcerated horses. This study aimed to report the prevalence of EGUS in sport horses and evaluate the association of plasma GGT activity to a diagnosis of EGUS. Fifty-nine horses, with and without EGUS clinical signs, from a cavalry regiment underwent gastroscopy and plasma biochemical analysis. EGUS, ESGD, and EGGD were found in 88 % (95 % confidence interval (95CI); 80 - 96 %), 80 % (95CI, 69 - 90), and 42 % (95CI, 30 - 55), respectively. A significant association was noted between EGUS prevalence and the squadron of the horse but not between EGUS or any of its components and plasma GGT activity. Horses affected by EGGD had higher average GGT activity (28.2 IU/L vs. 9.7 IU/L). Receiver operating characteristic curve analysis suggested a plasma GGT threshold of 21 IU/L for diagnosing EGGD (sensitivity and specificity of 80 % and 100 % respectively). However, some limitations were identified in this study including sample size, failure to visualise the pylori in some horses and body condition score as a confounding factor. Further studies are needed to evaluate the potential of plasma GGT activity in supporting a diagnosis of EGUS.
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Affiliation(s)
- Lorenzo Hardy
- École Nationale Vétérinaire d'Alfort, 7, avenue du Général de Gaulle, 94700, Maisons-Alfort, France; 1(er) Centre médical des armées, 23(e) groupe vétérinaire, 18, boulevard Henri IV, 75004, Paris, France.
| | - Marion Martin
- 1(er) Centre médical des armées, 23(e) groupe vétérinaire, 18, boulevard Henri IV, 75004, Paris, France
| | - Charles Barré
- Nutrition Équine, 1, Place de l'Église, 72360, Verneil-le-Chétif, France
| | - Ludovic Tanquerel
- École Nationale Vétérinaire d'Alfort, CHUV-EQ, ACAP3, 1504, Route de l'Église, 14430, Goustranville, France
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3
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Budak S. Haemodialysis distress thermometer scale: Turkish validity and reliability study. Int Urol Nephrol 2025:10.1007/s11255-025-04574-3. [PMID: 40397363 DOI: 10.1007/s11255-025-04574-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 05/10/2025] [Indexed: 05/22/2025]
Abstract
PURPOSE This study aimed to translate and adapt the "Haemodialysis Distress Thermometer Scale" (HDDT) into Turkish and assess its validity and reliability. METHODS This study collected data from 223 haemodialysis patients across three public hospitals in Kütahya province, Türkiye, over a seven-week period. RESULTS In this study, the content validity index of the scale was determined to be 0.96. Validity analysis results indicated that factor loadings ranged between 0.45 and 0.82, the total variance explained was 59.25%, and the fit indices were X2/df = 1.149 and RMSEA = 0.026. Reliability analysis showed that the total Cronbach's α coefficient was 0.80, with item-total correlation coefficients ranging from 0.37 to 0.73. The cut-off score for the HDDT barometer was identified as 6.5. The final structure of the HDDT scale comprised 40 items, four factors, and an 11-point barometer, consistent with the original scale. CONCLUSION The Turkish version of the HDDT is a valid and reliable instrument for assessing distress in patients undergoing haemodialysis treatment. It may serve as a valuable tool for nurses in identifying and addressing patient distress during haemodialysis care.
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Affiliation(s)
- Serkan Budak
- Simav Vocational School of Health Services, Department of Health Care Services, Kütahya Health Sciences University, Kütahya, Türkiye.
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4
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Drouet J, López-Medina C, Molto A, Granger B, Fautrel B, Gaujoux-Viala C, Kiltz U, Dougados M, Gossec L. Global health in axial spondyloarthritis: thresholds for the Assessment of SpondyloArthritis international Society Health Index and the EuroQol score: analysis of the ASAS-PerSpA study. Scand J Rheumatol 2025; 54:175-183. [PMID: 39679471 DOI: 10.1080/03009742.2024.2424085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 10/29/2024] [Indexed: 12/17/2024]
Abstract
OBJECTIVES In axial spondyloarthritis (axSpA), patient-perceived quality of life/global functioning and health (GH) can be assessed using disease-specific [Assessment of SpondyloArthrit is international Society Health Index (ASAS-HI)] or generic [(3-level EuroQol 5 Dimensions (EQ-5D-3L)] scores. Our objectives were to explore the link between these scores and to define thresholds for good and poor GH. METHOD We conducted a post-hoc analysis of the cross-sectional ASAS-PerSpA study for patients fulfilling ASAS criteria for axSpA. The ASAS-HI and EQ-5D scores were analysed visually (distribution, scatterplot) and through Spearman correlation and agreement (deciles). To determine cut-offs for good and poor GH on EQ-5D based on the validated ≤5 and ≥12 cut-offs for ASAS-HI, respectively, receiver operating characteristics (ROC) curves and distribution-based methods were applied. Validity was assessed using crude concordance and prevalence-adjusted bias-adjusted kappa; discordance between groups was explored. RESULTS In 2651 patients (median age 41.0 years, 66.5% men), the correlation between ASAS-HI and EQ-5D was high (r = -0.73) and agreement (between deciles) was moderate (weighted kappa = 0.51). Both ROC areas under the curve were 0.86; thresholds of 0.69 and 0.54 for EQ-5D were chosen for good and poor GH, respectively. Crude concordances and agreement were satisfactory (0.80-0.81 and 0.60-0.61, respectively). The EQ-5D cut-off for good GH performed better than that for poor GH. CONCLUSION ASAS-HI and EQ-5D were highly correlated but did not fully overlap. We propose EQ-5D thresholds corresponding to the ASAS-HI thresholds for good and poor GH; however, caution is needed when assessing poor GH with EQ-5D. These findings will be useful to compare GH when only one of the outcome measures is available.
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Affiliation(s)
- Jms Drouet
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France
| | - C López-Medina
- Reina Sofia University Hospital, IMIBIC, University of Córdoba, Córdoba, Spain
| | - A Molto
- Rheumatology Department, Cochin Hospital, Paris, France
- INSERM U-1183, CRESS, Université Paris Cité, Paris, France
| | - B Granger
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France
- Public Health Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - B Fautrel
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France
- Rheumatology Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - C Gaujoux-Viala
- Rheumatology Department, IDESP Univ Montpellier, INSERM, CHU Nîmes, Montpellier, France
| | - U Kiltz
- Rheumazentrum Ruhrgebiet, Ruhr Universität Bochum, Herne, Germany
| | - M Dougados
- Rheumatology Department, Cochin Hospital, Paris, France
- INSERM U-1183, CRESS, Université Paris Cité, Paris, France
| | - L Gossec
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France
- Rheumatology Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
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Pirayeh N, Shahoori F, Goharpey S, Mostafaee N. Responsiveness of a Persian version of the international knee documentation committee and the anterior cruciate ligament-quality of life questionnaires in athletes with anterior cruciate ligament reconstruction following physiotherapy intervention. Physiother Theory Pract 2025; 41:959-967. [PMID: 39099189 DOI: 10.1080/09593985.2024.2388111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/22/2024] [Accepted: 07/22/2024] [Indexed: 08/06/2024]
Abstract
INTRODUCTION The International Knee Documentation Committee (IKDC) and Anterior Cruciate Ligament - Quality of Life Questionnaire (ACL-QOL) are frequently used patient-reported instruments designed for individuals with anterior cruciate ligament reconstruction (ACL-R). PURPOSE To evaluate responsiveness and determine minimal important change (MIC) for the Persian-version of IKDC and ACL-QOL in athletes with ACL-R following physiotherapy intervention. METHOD One hundred athletes with ACL-R, undergoing 16-week physiotherapy completed IKDC and ACL-QOL at weeks 4 and 20 post ACL-R. Participants also rated their overall changes on a 7-point global rating of change at follow-up. Responsiveness was evaluated using the receiver operating characteristics (ROC) curve and correlation analysis. In addition, the minimal important change (MIC) was determined on the ROC curve. RESULTS Acceptable responsiveness was reached by the IKDC and most of the subscales of ACL-QOL (area under the ROC curve (AUC) of 0.72-0.79). Also, the subscale of Lifestyle issues of ACL-QOL (AUC of 0.81 (95% CI = 0.72-0.89) and the overall of ACL-QOL (AUC of 0.87 (95% CI = 0.80-0.93) showed the good level of responsiveness. The MIC scores of IKDC and the Overall ACL-QOL were determined 25 and 26 points, respectively. CONCLUSION The IKDC and ACL-QOL questionnaires have adequate responsiveness and are able to measure the change in athletes with ACL-R following a 16-week physiotherapy intervention.
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Affiliation(s)
- Nahid Pirayeh
- Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Physiotherapy, School of Rehabilitation Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Fatemeh Shahoori
- Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Shahin Goharpey
- Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Physiotherapy, School of Rehabilitation Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Neda Mostafaee
- Department of Physiotherapy, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
- Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Roussel T, Dartus J, Pasquier G, Duhamel A, Preda C, Migaud H, Putman S. Can the minimal clinically important difference (MCID) for the Oxford score, KOOS and its derivatives be identified in a French sample of total knee arthroplasties? Orthop Traumatol Surg Res 2025; 111:103965. [PMID: 39089421 DOI: 10.1016/j.otsr.2024.103965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 06/28/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024]
Abstract
CONTEXT To assess the effect of a surgical procedure on a patient, it is conventional to use clinical scores before and after the procedure, but it is increasingly common and recommended to weight the results of these scores with the notion of minimal clinically important difference ("MCID"). This MCID should be determined using either the data distribution method based on score variation, or the anchor method, which uses an external question to categorize the results. MCIDs vary from one population to another, and to our knowledge there has been no investigation in France for total knee arthroplasties (TKAs). We therefore conducted a prospective study on a population of TKAs in order to: 1) Define MCID in France on a population of TKAs for the Oxford score, KOOS (Knee injury and Osteoarthritis Outcome Score) and its derivatives, 2) Determine whether MCID for these scores in France is comparable to results in the literature. HYPOTHESIS Is the MCID for total knee arthroplasty in France comparable to other results in the literature? MATERIAL AND METHOD This was a prospective observational study in which 218 patients (85 men, 133 women) with a mean age of 72 years [27-90] who had undergone a primary TKA out of 300 initially included responded, before and after surgery, to the Oxford-12, KOOS and Forgotten Joint Score (FJS) questions (mean follow-up 24 months). MCID was calculated using the distribution method as well as the anchor method ("improvement 1 to 5" and "improvement yes or no"). RESULTS At a mean follow-up of 24 months [18-36], the Oxford-12 score increased from 16 ± 8 [0-41] to 34 ± 11 [6-48] (p < 0.001), all components of the KOOS score were improved and the FJS at follow-up was 47 ± 32 [0-100]. For the anchor "improvement 1 to 5", there were 14 unimproved patients, 23 patients in identical condition and 179 patients improved by surgery. For the anchor "are you improved yes/no", there were 8 unimproved patients, 22 in identical condition and 187 surgically-improved patients. The mean MCID for all methods (anchor method and distribution) was 10 [7-13] for Oxford-12, 12 [12-12] for KOOS Symptom, 14 [12-17] for KOOS Pain, 12 [11-14] for KOOS Function, 14 [12-16] for KOOS Sport, 15 [15-16] for KOOS Quality of Life (QOL), 11 [10-12] for KOOS 12, 15 [12-18] for KOOS 12 Pa in. 12 [12-13] for KOOS 12 Function, 15 [15-15] for KOOS 12 QOL, 14 [13-14] for KOOS Physical Function Short-form (PS) and 14 [13-16] for KOOS Joint Replacement (JR). DISCUSSION The MCID for the Oxford-12, KOOS and its derivatives scores in a French population is comparable to that observed in other populations in the literature. LEVEL OF EVIDENCE IV; prospective study without control group.
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Affiliation(s)
- Tom Roussel
- CHU Lille, Service d'Orthopédie, Place de Verdun, Hôpital Salengro, F-59000 Lille, France; Lille University, 59000, France.
| | - Julien Dartus
- CHU Lille, Service d'Orthopédie, Place de Verdun, Hôpital Salengro, F-59000 Lille, France; Lille University, 59000, France
| | - Gilles Pasquier
- CHU Lille, Service d'Orthopédie, Place de Verdun, Hôpital Salengro, F-59000 Lille, France; Lille University, 59000, France
| | - Alain Duhamel
- Lille University, 59000, France; Univ. Lille, CHU Lille, ULR2694-METRICS : évaluation des technologies de santé et des pratiques médicales, F-59000 Lille, France; CHU Lille, Department of Biostatistics, F-59000 Lille, France
| | - Cristian Preda
- Lille University, 59000, France; Laboratory of Mathematics Paul Painlevé, UMR CNRS 8524, University of Lille, France; Lille Catholics Hospitals, Biostatistics Department Delegation for Clinical Research and Innovation, Lille Catholic University, Lille, France
| | - Henri Migaud
- CHU Lille, Service d'Orthopédie, Place de Verdun, Hôpital Salengro, F-59000 Lille, France; Lille University, 59000, France
| | - Sophie Putman
- CHU Lille, Service d'Orthopédie, Place de Verdun, Hôpital Salengro, F-59000 Lille, France; Lille University, 59000, France; Univ. Lille, CHU Lille, ULR2694-METRICS : évaluation des technologies de santé et des pratiques médicales, F-59000 Lille, France; CHU Lille, Department of Biostatistics, F-59000 Lille, France
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7
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Capelusnik D, Ramiro S, Nikiphorou E, Maksymowych WP, Magrey MN, Marzo-Ortega H, Boonen A. Unacceptable Work State in Rheumatoid Arthritis: Establishment of Thresholds for Presenteeism and Clinical Measurement Instruments. J Rheumatol 2025; 52:436-443. [PMID: 39892889 DOI: 10.3899/jrheum.2024-0833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2025] [Indexed: 02/04/2025]
Abstract
OBJECTIVE We aimed to identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed patients with rheumatoid arthritis (RA) and whether those thresholds can predict future adverse work outcomes (AWOs). Additionally, we assessed the performance of presenteeism thresholds previously established in axial spondyloarthritis (axSpA) among patients with RA for the same instruments. METHODS Data from the multinational Patient-Reported Outcomes in Employment Study in Rheumatoid Arthritis (RA-PROSE) study were used. Thresholds to determine when patients consider themselves in an "unacceptable work state" were calculated at baseline for 4 instruments assessing presenteeism and for the patient global assessment of RA-related pain. Different approaches derived from the receiver-operating characteristic methodology were used. Accuracy of thresholds to predict AWO throughout 12 months was assessed and previously developed presenteeism thresholds for axSpA were also tested. RESULTS A total of 104 employed patients were included: 15% of the patients considered themselves in an unacceptable work state, of which 7 (7%) had at least 1 AWO over 12 months. Thresholds of all instruments specifically developed in RA showed good performance vs the external criterion (area under the curve [AUC] > 0.75), except for the Quantity and Quality (QQ) method (AUC 0.62). The available axSpA thresholds were more accurate by reducing overestimation. The final optimal thresholds were Work Productivity and Activity Impairment Questionnaire (WPAI)-presenteeism ≥ 40, QQ method < 97, Workplace Activity Limitations Scale ≥ 0.75, 25-item Work Limitations Questionnaire with modified physical demands scale ≥ 29, and pain intensity ≥ 4. For AWO over 12 months, pain and WPAI performed best in predicting AWO. CONCLUSION The final thresholds to assess unacceptable presenteeism for axSpA were also chosen as most accurate for use in RA. In addition, accurate thresholds of pain reflecting unacceptable work state are available.
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Affiliation(s)
- Dafne Capelusnik
- D. Capelusnik, MD, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands, and Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;
| | - Sofia Ramiro
- S. Ramiro, MD, PhD, Department of Rheumatology, Leiden University Medical Center, Leiden, and Department of Rheumatology, Zuyderland Medical Center, Heerlen, the Netherlands
| | - Elena Nikiphorou
- E. Nikiphorou, MD, PhD Centre for Rheumatic Diseases, King's College London, and Department of Rheumatology, King's College Hospital, London, UK
| | - Walter P Maksymowych
- W.P. Maksymowych, MD, PhD, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Marina Nighat Magrey
- M. Nighat Magrey, MD, Department of Rheumatology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Helena Marzo-Ortega
- H. Marzo-Ortega, MD, PhD, National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, LTHT, and LIRMM, University of Leeds, Leeds, UK
| | - Annelies Boonen
- A. Boonen, MD, PhD, CAPHRI, Maastricht University, and Department of Rheumatology, Maastricht University Medical Center, Maastricht, the Netherlands
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Miller CJ, Farrar JT. Methodology for determining minimally clinically important differences in acute pain intensity with the double stopwatch technique. THE JOURNAL OF PAIN 2025; 30:104759. [PMID: 39689766 DOI: 10.1016/j.jpain.2024.104759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 12/04/2024] [Accepted: 12/11/2024] [Indexed: 12/19/2024]
Abstract
Minimum clinically important differences (MCIDs) in acute pain intensity have not been well established. Conventional approaches for estimating MCIDs require an independent reference scale, with a threshold that must be presumed to accurately classify meaningful change in pain for all study participants, to serve as an anchor. The double stopwatch technique is the gold standard for measuring the time to meaningful relief, where participants actively press the second stopwatch when they experience pain relief that is meaningful to them. This technique eliminates the problem of misclassification with arbitrary anchors at a single time point, but the censored nature of the data is not amenable for determining MCIDs using standard methods. We propose a stopwatch-based MCID methodology that employs the double stopwatch technique to identify individualized thresholds for meaningful change in pain. This approach enables direct classification of changes in pain for each participant based on whether they perceived the change as meaningful and whether it exceeded the study cut-off being tested. Pain values of participants who do not achieve meaningful relief are incorporated into the analysis to address censoring and avoid bias. The performance (e.g., sensitivity, specificity) of different thresholds to serve as an MCID can be estimated using standard approaches with variance estimates derived by cluster bootstrapping. The advantages of the stopwatch-based MCID methodology are illustrated relative to a conventional approach using data from a randomized trial in third molar extraction. PERSPECTIVE: This article describes a methodology for determining MCIDs using the double stopwatch technique, the gold standard for assessing meaningful changes in acute pain. This methodology can be used to establish MCIDs in different acute pain settings, providing a useful basis to evaluate the meaningfulness of clinical trial results.
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Affiliation(s)
- Christopher J Miller
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
| | - John T Farrar
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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9
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Waikar SS, Mogg R, Baker AF, Frendl G, Topper M, Adler S, Sultana S, Zhao R, King NMP, Piccoli SP, Sauer JM, Hoffmann S, Nunes I, Sistare FD. Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury. Clin Pharmacol Ther 2025; 117:1272-1283. [PMID: 39754474 DOI: 10.1002/cpt.3531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 11/26/2024] [Indexed: 01/06/2025]
Abstract
Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days. Using receiver-operating characteristics curves, "statistically significant thresholds" established peak longitudinal changes for 8 biomarkers to differentiate mesothelioma patients who developed acute kidney injury (AKI) from normal healthy volunteers. We also assessed "medically significant thresholds" to differentiate mesothelioma patients who did vs. did not develop AKI. Statistically and medically significant thresholds for a fold-change from baseline of urine creatinine (UCr)-normalized values were established for 6 biomarkers: clusterin (2.2, 5.1); osteopontin (3.1, 7.1); N-acetyl-ß-D-glucosaminidase (2.7, 8.1); kidney injury molecule-1 (4.3, 7.5); cystatin C (1.8, 4.5); neutrophil gelatinase-associated lipocalin (2.9, 7.8). For urine albumin and total protein, thresholds were established based on UCr-normalized absolute values: (> upper limit normal, > 10× upper limit normal). Statistically significant thresholds for all biomarkers outperformed eGFR at discriminating mesothelioma subjects exposed to cisplatin from healthy volunteers, demonstrating their utility for enhancing safe drug development. Medically significant thresholds provide perspective on when patients begin to exhibit AKI. These studies have established guideposts for confirmatory studies with additional cohorts and nephrotoxicants to formally qualify the selected biomarkers with worldwide regulatory authorities.
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Affiliation(s)
- Sushrut S Waikar
- Department of Medicine and Section of Nephrology, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts, USA
| | - Robin Mogg
- Merck & Co., Inc., Rahway, New Jersey, USA
| | | | - Gyorgy Frendl
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | | | | | - Runqi Zhao
- Department of Medicine and Section of Nephrology, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts, USA
| | | | | | | | - Steve Hoffmann
- Foundation for the National Institutes of Health, North Bethesda, Maryland, USA
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10
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Berge MB, Kessler J, Staff AC, Jacobsen AF. The diagnostic accuracy of different fetal blood sample lactate cutoffs in labor, utilizing the StatStrip Xpress® lactate-meter: A population-based observational study. Acta Obstet Gynecol Scand 2025. [PMID: 40304212 DOI: 10.1111/aogs.15140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 03/18/2025] [Accepted: 04/12/2025] [Indexed: 05/02/2025]
Abstract
INTRODUCTION A recent study recommended 5.2 mmol/L as a cutoff for fetal blood sample (FBS) lactate in labor for the StatStrip Lactate®/Lactate Xpress® lactate meter. In the present study, we validated FBS lactate cutoffs in a larger population-based setting, with different CTG guidelines, testing external validity. MATERIAL AND METHODS We conducted a prospective population-based study at Oslo University Hospital, Ullevål, Norway, a tertiary referral obstetric department with 7000 annual deliveries. Women with a singleton fetus in cephalic presentation in gestational week ≥36 + 0 were included in the analyses. We used ROC curves to calculate the area under the curve (AUC) and estimate the optimal cutoff for the following adverse neonatal outcomes: Umbilical cord pH ≤7.10, umbilical cord pH ≤7.05, metabolic acidosis (pH <7.0 and Base deficitextracellular fluid > 12 mmol/L), 1-minute Apgar score <4, 5-min Apgar score <7, hypoxic ischemic encephalopathy, and transfer to the neonatal intensive care unit. Analyses were restricted to women with a FBS lactate within 25 min prior to delivery. The study is registered in clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT04779294). RESULTS Of 7816 included women, 1466 (19%) had a FBS lactate measurement within 25 min prior to delivery. The calculated optimal cutoff for FBS lactate varied by outcomes: 5-min Apgar score <7: AUC 0.69 (0.57-0.80), cutoff 4.0 mmol/L; metabolic acidosis: AUC 0.92 (0.78-1.00), cutoff 7.0 mmol/L; hypoxic ischemic encephalopathy: AUC 0.95 (0.86-1.00), cutoff 4.7 mmol/L. Sensitivity increased for some of the outcomes with a decreasing cutoff. Specificity increased for all outcomes with an increasing cutoff. CONCLUSIONS We consider an FBS lactate cutoff of ≥5.2 mmol/L a good balance between high sensitivity for adverse neonatal outcomes and an acceptable number of needed interventions.
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Affiliation(s)
- Magnus B Berge
- Division of Gynaecology and Obstetrics, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Jørg Kessler
- Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Anne Cathrine Staff
- Division of Gynaecology and Obstetrics, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Anne Flem Jacobsen
- Division of Gynaecology and Obstetrics, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Hassanzad M, Hajian-Tilaki K, Bouzari Z, Yazdani S. Comparison of methods of optimal cut-point selection for biomarkers in diagnostic medicine: a simulation study with application of clinical data in health informatics. BMC Res Notes 2025; 18:193. [PMID: 40269988 PMCID: PMC12020263 DOI: 10.1186/s13104-025-07245-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/07/2025] [Indexed: 04/25/2025] Open
Abstract
OBJECTIVES Several methods of cut-point selection for biomarkers have been suggested in biomedical research but the superiority of them over others was not studied comprehensively under different pairs of distributions, degree of overlap, and the ratio of sample sizes. This simulation study was aimed to compare five popular methods with application of clinical examples. RESULTS The data of simulation was generated from the 12 configurations of binormal, bigamma, and biexponential pairs with different sample sizes The results showed that the four popular methods of Youden, Euclidean, Product, and Index of Union (IU) yielded identical optimal cut-point under binormal model with homoscedastic. While, with high AUC, the Youden may produce less bias and MSE, but for moderate and low AUC, Euclidean has less bias and MSE than other methods. The IU yielded more precise findings than the Youden for moderate and low AUC in binormal pairs, but its performance was lower with skewed distributions. In contrast, the cut-points produced by diagnostic odds ratio (DOR) were extremely high with low sensitivity and high MSE and bias. The results of clinical data showed that when AUC > 0.95, the five methods may produce identical cut-point, but DOR yields an extremely high value of cut-point for AUC < 0.95.
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Affiliation(s)
- Mojtaba Hassanzad
- Student Research Center, Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Karimollah Hajian-Tilaki
- Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran.
- Social Determinant Health Research Center, Research Institute, Babol University of Medical Sciences, Babol, Iran.
| | - Zinatossadat Bouzari
- Department of Obstetrics and Gynecology, Ayatollah Rohani Hospital, Babol University of Medical Sciences, Babol, Iran
| | - Shahla Yazdani
- Department of Obstetrics and Gynecology, Ayatollah Rohani Hospital, Babol University of Medical Sciences, Babol, Iran
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12
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Bär S, Knuuti J, Saraste A, Klén R, Kero T, Nabeta T, Bax JJ, Danad I, Nurmohamed NS, Jukema RA, Knaapen P, Maaniitty T. Derivation and Validation of an Artificial Intelligence-Based Plaque Burden Safety Cut-Off for Long-Term Acute Coronary Syndrome from Coronary Computed Tomography Angiography. Eur Heart J Cardiovasc Imaging 2025:jeaf121. [PMID: 40243706 DOI: 10.1093/ehjci/jeaf121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/29/2025] [Accepted: 04/01/2025] [Indexed: 04/18/2025] Open
Abstract
AIMS Artificial intelligence (AI) has enabled accurate and fast plaque quantification from coronary computed tomography angiography (CCTA). However, AI detects any coronary plaque in up to 97% of patients. To avoid overdiagnosis, a plaque burden safety cut-off for future coronary events is needed. METHODS AND RESULTS Percent atheroma volume (PAV) was quantified with artificial intelligence-guided quantitative computed tomography (AI-QCT) in a blinded fashion. Safety cut-off derivation was performed in the Turku CCTA registry, Finland, and pre-defined as ≥90% sensitivity for acute coronary syndrome (ACS). External validation was performed in the Amsterdam CCTA registry, Netherlands. In the derivation cohort, 100/2271 (4.4%) patients experienced ACS (median follow-up 6.9 years). A threshold of PAV ≥2.6% was derived with 90.0% sensitivity and negative predictive value (NPV) of 99.0%. In the validation cohort 27/568 (4.8%) experienced ACS (median follow-up 6.7 years) with PAV ≥2.6% showing 92.6% sensitivity and 99.0% NPV for ACS. In the derivation cohort, 45.2% of patients had PAV <2.6% vs. 4.3% with PAV 0% (no plaque) (p<0.001) (validation cohort: 34.3% PAV <2.6% vs. 2.6% PAV 0%; p<0.001). Patients with PAV ≥2.6% had higher adjusted ACS rates in the derivation (HR 4.65, 95% CI 2.33-9.28, p<0.001) and validation cohort (HR 7.31, 95% CI 1.62-33.08, p=0.010), respectively. CONCLUSION This study suggests that PAV up to 2.6% quantified by AI is associated with low ACS risk in two independent patient cohorts. This cut-off may be helpful for clinical application of AI-guided CCTA analysis, which detects any plaque in up to 96-97% of patients.
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Affiliation(s)
- Sarah Bär
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
- Bern University Hospital Inselspital, Department of Cardiology, Bern, Switzerland
| | - Juhani Knuuti
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
- Department of Clinical Physiology, Nuclear Medicine, and PET, Turku University Hospital, Turku, Finland
| | - Antti Saraste
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
- Heart Center, Turku University Hospital and University of Turku, Turku, Finland
| | - Riku Klén
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
| | - Tanja Kero
- Nuclear Medicine & PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Takeru Nabeta
- Leiden University Medical Center, Department of Cardiology, Leiden, the Netherlands
| | - Jeroen J Bax
- Leiden University Medical Center, Department of Cardiology, Leiden, the Netherlands
| | - Ibrahim Danad
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Nick S Nurmohamed
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Ruurt A Jukema
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Paul Knaapen
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Teemu Maaniitty
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
- Department of Clinical Physiology, Nuclear Medicine, and PET, Turku University Hospital, Turku, Finland
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13
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Ku KC, Zhong J, Song E, Fong CHY, Lam KSL, Xu A, Lee CH, Cheung CYY. Clinical utility of glycated albumin and 1,5-anhydroglucitol in the screening and prediction of diabetes: A multi-center study. World J Diabetes 2025; 16:102867. [PMID: 40236844 PMCID: PMC11947923 DOI: 10.4239/wjd.v16.i4.102867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/24/2024] [Accepted: 02/12/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Despite being the gold standard, the use of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) for diagnosing dysglycemia is imperfect. In particular, a low level of agreement between HbA1c and FPG in detecting prediabetes and diabetes has led to difficulties in clinical interpretation. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) may potentially serve as biomarkers for the detection and prediction of diabetes, as well as glycemic monitoring. AIM To explore the diagnostic performance of GA and 1,5-AG for screening dysglycemia; assess whether they can be used for glycemic monitoring in Chinese morbidly-obese patients; and examine their predictive ability for incident diabetes in a Chinese community-based cohort. METHODS GA and 1,5-AG concentrations were measured in 462 morbidly-obese patients from the Obese Chinese Cohort (OCC). A sub-group of diabetes subjects (n = 24) was prospectively followed-up after bariatric surgery. Differences between baseline and post-surgery biomarker values were converted to percentage change from baseline to assess the response to glycemic control. Predictive ability of the biomarkers was assessed in 132 incident diabetes cases and 132 matched non-diabetes controls in the community-based Cardiovascular Risk Factor Prevalence Study (CRISPS). A prediction model was developed and compared with clinical models based on conventional risk factors. RESULTS GA exhibited an excellent diagnostic value with an area under the receiver operating characteristic curve (AUC) of 0.919 (95%CI: 0.884-0.955) for identifying diabetes and a high agreement in the classification of diabetes with both FPG and HbA1c in the OCC. GA demonstrated the fastest response to glycemic control. In CRISPS, the 'B3A' prediction model, which consisted of body mass index (BMI) and 3 biomarkers (HbA1c, GA and 1,5-AG), achieved a comparable predictive value [AUC (95%CI): 0.793 (0.744-0.843)] to that of a clinical model comprising BMI, HbA1c, FPG and 2-hour glucose (2hG) [AUC (95%CI): 0.783 (0.733-0.834); DeLong P value = 0.736]. The 'B3A' was significantly superior to a clinical model including BMI, HbA1c, FPG and triglycerides [AUC (95%CI): 0.729 (0.673-0.784); DeLong P value = 0.027]. CONCLUSION GA and 1,5-AG have the potential to act as robust biomarkers for the screening and risk prediction of diabetes. FPG and 2hG may be replaced by GA and 1,5-AG in future diabetes predictions.
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Affiliation(s)
- Kam-Ching Ku
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Junda Zhong
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Erfei Song
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Carol Ho-Yi Fong
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Karen Siu-Ling Lam
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Aimin Xu
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Chi-Ho Lee
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Chloe Yu-Yan Cheung
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
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Nakamura K, Kurobe Y, Sue K, Sakurai S, Sasaki T, Yamamoto S, Ushiyama N, Taga M, Momose K. Impact of early postoperative ambulation on gait recovery after hip fracture surgery: a multicenter cohort study. Sci Rep 2025; 15:12893. [PMID: 40234556 PMCID: PMC12000283 DOI: 10.1038/s41598-025-97632-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 04/07/2025] [Indexed: 04/17/2025] Open
Abstract
The study aimed to investigate the effect of early postoperative ambulation on gait recovery at the initial postoperative week and at discharge after hip fracture surgery in older patients. In this prospective cohort study, 882 patients aged ≥ 65 years from 10 acute hospitals in Japan were divided into early-ambulation (EA) (ambulation initiated on postoperative day 1 or 2) and late-ambulation (LA) (ambulation initiated on postoperative day 3 or later) groups. The Functional Independence Measure (FIM) was assessed 1 day postoperatively, 1 week postoperatively, and at discharge. Independent walking regardless of walking aids was defined as walking FIM ≥ 5. Multivariate logistic regression analysis and a generalized linear mixed model, accounting for inter-hospital variability, determined whether EA affected independent walking at 1 week postoperatively and at discharge. The number of patients walking independently 1 week postoperatively and at discharge was 156 (17.7%) and 292 (33.1%), respectively. On multivariate logistic regression analysis, EA was associated with independent walking at 1 week postoperatively (odds ratio [OR] 3.27; 95% confidence interval [CI] 2.17-4.94; P < 0.0001) and at discharge (OR 3.33; 95% CI 2.38-4.69; P < 0.0001). This study highlights the importance of EA in promoting postoperative independent walking, regardless of hospital setting.
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Affiliation(s)
- Keisuke Nakamura
- Department of Physical Therapy, School of Health Sciences, Shinshu University, Matsumoto, Nagano, 390-8621, Japan.
| | - Yasushi Kurobe
- Department of Rehabilitation, Fujimi-Kogen Hospital, Fujimi-Kogen Medical Center, Fujimi Town, Nagano, 399-0214, Japan
| | - Keita Sue
- Department of Rehabilitation, JA Nagano Kouseiren, Kakeyu-Misayama Rehabilitation Center Kakeyu Hospital, Ueda, Nagano, 386-0322, Japan
| | - Shinichi Sakurai
- Department of Rehabilitation, Saku Central Hospital, Saku, Nagano, 385-0051, Japan
| | - Tomohiro Sasaki
- Department of Rehabilitation, Matsumoto City Hospital, Matsumoto, Nagano, 390-1401, Japan
| | - Shuhei Yamamoto
- Department of Rehabilitation, Shinshu University Hospital, Matsumoto, Nagano, 390-8621, Japan
| | - Naoko Ushiyama
- Department of Rehabilitation, Fujimi-Kogen Hospital, Fujimi-Kogen Medical Center, Fujimi Town, Nagano, 399-0214, Japan
| | - Masahito Taga
- Department of Rehabilitation, Ina Central Hospital, Ina, Nagano, 396-8555, Japan
| | - Kimito Momose
- Department of Physical Therapy, School of Health Sciences, Shinshu University, Matsumoto, Nagano, 390-8621, Japan
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Agulnik A, Robles‐Murguia M, Chen Y, Muñiz‐Talavera H, Pham L, Carrillo A, Cardenas‐Aguirre A, Costa J, Mendez Aceituno A, Acuña Aguirre C, Aguilar Roman AB, Alvarez Arellano SY, Andrade Sarmiento LA, Arce Cabrera D, Blasco Arriaga EE, De León Gutiérrez CM, Diaz‐Coronado R, Diniz Borborema MDC, do Nascimento Othero Campacci M, Drumond Alberto L, Gonzalez NS, Herrera Almanza M, Jimenez Antolinez V, Laffont Ortiz MD, Lemos De Mendonça E. Fontes L, López Facundo NA, López Vázquez CB, Lozano Lozano IM, Mijares Tobias JM, Mora Robles LN, Noriega Acuña B, Endo Marques FP, Pérez Fermín CK, Quijano Lievano ML, Ribeiro Pereira Aguiar De Paula A, Rios L, Rivera J, Sahonero MA, Salas Mendoza B, Sánchez‐Martín M, Sepúlveda Ramírez J, Soto Chávez V, Velásquez Cabrera DM, Villanueva Hoyos EE, Zuñiga Quijano LY, Devidas M, Rodriguez‐Galindo C, for the Escala de Valoracion de Alerta Temprana Study Group. Multilevel mortality risk factors among pediatric hematology-oncology patients with deterioration. Cancer 2025; 131:e35818. [PMID: 40193253 PMCID: PMC11975202 DOI: 10.1002/cncr.35818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 01/30/2025] [Accepted: 02/20/2025] [Indexed: 04/09/2025]
Abstract
BACKGROUND Hospitalized pediatric hematology-oncology patients have frequent clinical deterioration events (CDEs) requiring intensive care unit (ICU) interventions and resulting in high mortality, particularly in resource-limited settings. This study identifies independent risk factors for CDE mortality in hospitals providing childhood cancer care in Latin America and Spain. METHODS Centers implemented a prospective CDE registry, defined as unplanned transfer to a higher level of care, use of ICU-level interventions on the ward, or nonpalliative ward death. The authors analyzed registry data from April 2017 to December 2022. The primary outcome was CDEs mortality, defined as death occurring during ICU admission, <24 hours of ICU discharge, or end of ward-based ICU interventions. Multilevel modeling identified event-, patient-, and hospital-level independent risk factors for CDE mortality. RESULTS Among 69 participating hospitals in 18 countries, 4134 CDEs were reported in 3319 pediatric hematology-oncology patients with an event mortality of 26.8% (1108 events). Of all CDEs, 33.7% used ICU interventions on the ward and 87.5% were transferred to a higher level of care. In multilevel modeling, significant independent risk factors for event mortality present at the start of deterioration included patient (disease relapse) and event (e.g., reason for hospital admission, use of ICU intervention on wards, abnormal lactate, platelets, or C-reactive protein, reason for deterioration, and number of organs with dysfunction); hospital factors were not significant predictors of mortality. CONCLUSIONS Hospitalized pediatric hematology-oncology patients with CDE have high mortality with significant variability across centers. Mortality, however, is largely driven by modifiable event-level factors, demonstrating the need for targeted interventions to improve survival.
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Affiliation(s)
- Asya Agulnik
- St. Jude Children's Research HospitalMemphisTennesseeUSA
| | | | - Yichen Chen
- St. Jude Children's Research HospitalMemphisTennesseeUSA
| | | | - Linh Pham
- St. Jude Children's Research HospitalMemphisTennesseeUSA
| | | | | | - Juliana Costa
- St. Jude Children's Research HospitalMemphisTennesseeUSA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Ligia Rios
- Hospital Nacional Edgardo Rebagliati MartinsLimaPerú
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Bella-Fernández M, Suero Suñé M, Ferrer-Mendieta A, Gil-Gómez de Liaño B. One factor to bind them all: visual foraging organization to predict patch leaving behavior with ROC curves. Cogn Res Princ Implic 2025; 10:16. [PMID: 40188319 PMCID: PMC11972240 DOI: 10.1186/s41235-025-00624-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 02/28/2025] [Indexed: 04/07/2025] Open
Abstract
Predicting quitting rules is critical in visual search: Did I search enough for a cancer nodule in a breast X-ray or a threat in a baggage airport scanner? This study examines the predictive power of search organization indexes like best-r, mean ITD, PAO, or intersection rates as optimal criteria to leave a search in foraging (looking for several targets among distractors). In a sample of 29 adults, we compared static and dynamic foraging. Also, we reanalyze data from diverse foraging tasks in the lifespan already published to replicate results. Using ROC curves, all results consistently show that organization measures outperform classic intake rates commonly used in animal models to predict optimal human quitting behavior. Importantly, a combination of organization and traditional intake rates within a unitary factor is the best predictor. Our findings open a new research line for studying optimal decisions in visual search tasks based on search organization.
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Affiliation(s)
- Marcos Bella-Fernández
- Universidad Autónoma de Madrid, Madrid, Spain
- UNIE Universidad, Madrid, Spain
- Universidad Pontificia de Comillas, Madrid, Spain
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17
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Ramsperger S, Witthöft M, Bräscher AK. Bridging the feedback implementation gap: A comparison of empirical and rational decision rules in naturalistic psychotherapy. Psychother Res 2025; 35:679-693. [PMID: 38607372 DOI: 10.1080/10503307.2024.2334047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 03/07/2024] [Accepted: 03/14/2024] [Indexed: 04/13/2024] Open
Abstract
Objective: Previous research indicates positive effects of feedback based on rational or empirical decision rules in psychotherapy. The implementation of these usually session-to-session-based feedback systems into clinical practice, however, remains challenging. This study aims to evaluate decision rules based on routine outcome monitoring with reduced assessment frequency. Method: Data routinely collected every 5-20 sessions of N = 3758 patients treated with CBT in an outpatient clinic (Msessions = 42.8, SD = 15.4) were used to develop feedback decision rules based on the expected treatment response and nearest neighbors approach, the reliable change index, and method of percental improvement. The detection of patients at risk of treatment failure served as primary endpoint. Results: Significantly lower reliable improvement, higher reliable deterioration rates, and smaller effect sizes were found for patients identified at risk of treatment failure by all rules. The nearest neighbors-based approach showed the highest sensitivity regarding the detection of reliably deteriorated cases. Conclusion: Consistent with previous research, the empirical models outperformed the rational rules. Still, the first-time used percental improvement-based rule also showed satisfactory results. Overall, the results point to the potential of basic feedback systems that might be easier to implement in practice than session-to-session based systems.
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Affiliation(s)
- Stephan Ramsperger
- Department for Clinical Psychology, Psychotherapy and Experimental Psychopathology, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Michael Witthöft
- Department for Clinical Psychology, Psychotherapy and Experimental Psychopathology, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Anne-Kathrin Bräscher
- Department for Clinical Psychology, Psychotherapy and Experimental Psychopathology, Johannes Gutenberg University Mainz, Mainz, Germany
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18
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Burger CD, Saunders H, Hodge DO, Safford RE, Helgeson SA, Moss JE, DuBrock HM, Cartin-Ceba R, Cajigas HR, Krowka MJ. Echocardiography Screening of Consecutive Patients With Portal Hypertension Referred to Mayo Clinic for Liver Transplant Evaluation. Mayo Clin Proc 2025; 100:668-679. [PMID: 39520417 DOI: 10.1016/j.mayocp.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 07/12/2024] [Accepted: 08/07/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE To determine the prevalence of portopulmonary hypertension in patients referred for liver transplant evaluation. METHODS Medical records were reviewed for 986 consecutive patients referred for liver transplant evaluation who were screened for pulmonary hypertension with echocardiography from February 1, 2021, to January 31, 2022, across 3 liver transplant centers. RESULTS Of 934 patients eligible for analysis, mean (SD) age was 57 (11) years, 558 (59.7%) were men, and 859 (92.0%) were White. Alcoholic cirrhosis and nonalcoholic steatohepatitis represented 640 (68.5%) of the liver diseases. Right ventricular systolic pressure estimated by echocardiography was 35 mm Hg or greater in 147 (15.7%) and less than 35 mm Hg in 475 (50.9%; unable to estimate in 312 [33.4%]). Right-sided heart catheterization was performed in 42 (4.5%) patients; hemodynamic profiles revealed that 12 (28.6%) did not have pulmonary hypertension, 15 (35.7%) had postcapillary venous pulmonary hypertension, 7 (16.7%) had portopulmonary hypertension, 6 (14.3%) had unclassifiable pulmonary hypertension, and 2 (4.8%) had combined pre- and postcapillary pulmonary hypertension. CONCLUSION The percentage of portopulmonary hypertension in patients referred for liver transplant was considerably lower, 7 of 934 (0.7%), than in previous studies, but the reason was unclear.
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Affiliation(s)
- Charles D Burger
- Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, Jacksonville, FL.
| | - Hollie Saunders
- Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Jacksonville, FL
| | - David O Hodge
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL
| | - Robert E Safford
- Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL
| | - Scott A Helgeson
- Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, Jacksonville, FL
| | - John E Moss
- Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, Jacksonville, FL
| | - Hilary M DuBrock
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | | | - Hector R Cajigas
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | - Michael J Krowka
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
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Shimada H, Doi T, Tsutsumimoto K, Makino K, Harada K, Tomida K, Morikawa M, Arai H. Combined effects of social isolation and loneliness on disability incidence in older adults. Arch Gerontol Geriatr 2025; 131:105749. [PMID: 39799619 DOI: 10.1016/j.archger.2025.105749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 12/18/2024] [Accepted: 01/02/2025] [Indexed: 01/15/2025]
Abstract
OBJECTIVES Relationships among social isolation, loneliness, and disability onset remain unclear. We investigated the distinct patterns of disability development among Japanese older adults who experience social isolation and loneliness. DESIGN This study applied a prospective observational approach. PARTICIPANTS Data from 4,716 community-dwelling independent older adults were analyzed. MEASUREMENTS The Japanese version of the University of California, Los Angeles Loneliness Scale Version 3 and the Social Isolation Scale were used to measure loneliness and social isolation, respectively. The long-term care insurer conducted monthly follow-ups with participants over two years to determine their care needs. Disability onset was defined as the point at which participants were certified by a care manager as requiring long-term care. RESULTS During the follow-up period, 265 participants (5.6 %) required long-term care insurance certification due to disability onset. The incidence of disability in the lonely and not lonely groups was 8.0 % and 4.5 %, respectively. In the socially isolated and not socially isolated groups, it was 7.1 % and 4.4 %, respectively. The Cox proportional hazards regression model revealed a significantly higher risk of disability incidence in the lonely and socially isolated groups. The high-risk group experiencing both loneliness and social isolation exhibited significantly higher hazard ratios than the low-risk group without these symptoms. CONCLUSIONS The results indicated that older adults experiencing both social isolation and loneliness were at high-risk for future disability incidence. This finding provides insight into the complex interplay between social factors and disability, which can contribute to the development of effective interventions to promote healthy aging and prevent disability.
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Affiliation(s)
- Hiroyuki Shimada
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan.
| | - Takehiko Doi
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan
| | - Kota Tsutsumimoto
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan
| | - Keitaro Makino
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan
| | - Kenji Harada
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan
| | - Kouki Tomida
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan
| | - Masanori Morikawa
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, Research Institute, National Centre for Geriatrics and Gerontology, Obu, Japan
| | - Hidenori Arai
- Centre for Gerontology and Social Science, National Centre for Geriatrics and Gerontology, Obu, Japan
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20
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Guimarães V, Sousa I, Correia MV. Detecting cognitive impairment in cerebrovascular disease using gait, dual tasks, and machine learning. BMC Med Inform Decis Mak 2025; 25:157. [PMID: 40170023 PMCID: PMC11963529 DOI: 10.1186/s12911-025-02979-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 03/18/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Cognitive impairment is common after a stroke, but it can often go undetected. In this study, we investigated whether using gait and dual tasks could help detect cognitive impairment after stroke. METHODS We analyzed gait and neuropsychological data from 47 participants who were part of the Ontario Neurodegenerative Disease Research Initiative. Based on neuropsychological criteria, participants were categorized as impaired (n = 29) or cognitively normal (n = 18). Nested cross-validation was used for model training, hyperparameter tuning, and evaluation. Grid search with cross-validation was used to optimize the hyperparameters of a set of feature selectors and classifiers. Different gait tests were assessed separately. RESULTS The best classification performance was achieved using a comprehensive set of gait metrics, measured by the electronic walkway, that included dual-task costs while performing subtractions by ones. Using a Support Vector Machine (SVM), we could achieve a sensitivity of 96.6%, and a specificity of 61.1%. An optimized threshold of 27 in the Montreal Cognitive Assessment (MoCA) revealed lower classification performance than the gait metrics, although differences in classification results were not significant. Combining the classifications provided by MoCA with those provided by gait metrics in a majority voting approach resulted in a higher specificity of 72.2%, and a high sensitivity of 93.1%. CONCLUSIONS Our results suggest that gait analysis can be a useful tool for detecting cognitive impairment in patients with cerebrovascular disease, serving as a suitable alternative or complement to MoCA in the screening for cognitive impairment.
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Affiliation(s)
- Vânia Guimarães
- Fraunhofer Portugal AICOS, Rua Alfredo Allen 455/461, Porto, 4200-135, Portugal.
- Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal.
| | - Inês Sousa
- Fraunhofer Portugal AICOS, Rua Alfredo Allen 455/461, Porto, 4200-135, Portugal
| | - Miguel Velhote Correia
- Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal
- INESC TEC, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal
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21
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Colledani D, Mikulincer M, Shaver PR, Meneghini AM. Using the K-Means Node Clustering Method and ROC Curve Analysis to Define Cut-Off Scores for the Caregiving System Scale. INTERNATIONAL JOURNAL OF PSYCHOLOGY 2025; 60:e70038. [PMID: 40059112 PMCID: PMC11891118 DOI: 10.1002/ijop.70038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 02/24/2025] [Accepted: 02/26/2025] [Indexed: 05/13/2025]
Abstract
This study was conducted to establish cut-off scores for the subscales of the Caregiving System Scale (CSS). Two samples of Italian adults (N's = 682 and 227) completed the CSS. In the first sample, K-means node clustering and ROC curve analyses were conducted. Four caregiving profiles were identified and cut-off scores were calculated for classifying participants into these profiles. In the second sample, participants completed the CSS and the Attachment Style Questionnaire. Findings supported the presence of unique CSS profiles and meaningful connections between them and attachment orientations. This work offers a method for determining cut-off scores when gold-standard measures needed to run ROC curve analyses are unavailable.
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Affiliation(s)
- Daiana Colledani
- Department of Psychology, Faculty of Medicine and PsychologySapienza University of RomeRomeItaly
| | - Mario Mikulincer
- Baruch Ivcher School of PsychologyReichman UniversityHerzliyaIsrael
| | - Phillip R. Shaver
- Department of PsychologyUniversity of California DavisDavisCaliforniaUSA
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22
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Farina A, Villagrán-García M, Abichou-Klich A, Benaiteau M, Bernard E, Campetella L, Cluse F, Desestret V, Dumez P, Fabien N, Goncalves D, Muñiz-Castrillo S, Picard G, Pinto AL, Rogemond V, Vogrig A, Joubert B, Honnorat J. Application of the anti-IgLON5 disease composite score to assess severity, clinical course, and mortality in a French cohort. J Neurol 2025; 272:273. [PMID: 40106089 PMCID: PMC11922985 DOI: 10.1007/s00415-025-13001-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 02/27/2025] [Indexed: 03/22/2025]
Abstract
Anti-IgLON5 disease presents with diverse symptoms, whose severity can be measured by the anti-IgLON5 disease composite score (ICS). This study applied the ICS to a retrospective anti-IgLON5 disease cohort (n = 52; median age 72 years, 63% male) diagnosed in the French Reference Center on Autoimmune Encephalitis (2016-2024), aiming to describe severity and clinical course, and to assess its potential to predict mortality. At diagnosis, the ICS distribution (median 18) aligned with previous publications and correlated with the time to diagnosis (median 19 months); all patients had symptoms in ≥ 2 ICS domains: bulbar (88%), sleep (84%), movement disorders (90%), cognition (64%), and/or other (78%). Of 46 patients with follow-up data, 7 (16%) died shortly after diagnosis; for the others, changes in the ICS mirrored the clinical course: at last visit, it decreased in improving patients (16/46, 35%; median 12 vs 17; p = 0.004), increased in worsening patients (11/39, 24%; median 26 vs 21; p = 0.006) and did not change significantly in stable patients (12/46, 26%; median 16 vs 15; p = 0.222). In the ROC analyses, 2-year mortality was predicted by the total ICS at diagnosis (AUC 69.51, 95% CI [50.19; 88.83]; optimal cut-off > 20, sensitivity 59%, specificity 77%), and by the bulbar score at diagnosis (AUC 74.68, 95% CI [56.17, 93.19]; optimal cut-off > 3, sensitivity 83%, specificity 62%). The ICS is a reproducible tool for assessing anti-IgLON5 disease severity and clinical course. Higher total and bulbar ICS at diagnosis are associated with increased mortality risk, underscoring the need for early and intensive management of bulbar dysfunction.
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Affiliation(s)
- Antonio Farina
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Macarena Villagrán-García
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Amna Abichou-Klich
- Service de Biostatistique et Bioinformatique, Hospices Civils de Lyon, Pôle Santé Publique, Lyon, France
| | - Marie Benaiteau
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Emilien Bernard
- French Reference Centre on Amyotrophic Lateral Sclerosis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France
| | - Lucia Campetella
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Florent Cluse
- French Reference Centre on Amyotrophic Lateral Sclerosis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France
- Electroneuromyography and Neuromuscular Diseases Unit, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France
| | - Virginie Desestret
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
| | - Pauline Dumez
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Nicole Fabien
- Service d'Immunologie, Centre de Biologie et Pathologie Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - David Goncalves
- Service d'Immunologie, Centre de Biologie et Pathologie Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Sergio Muñiz-Castrillo
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- Department of Neurology, Hospital Universitario, 12 de Octubre, Madrid, Spain
| | - Géraldine Picard
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Anne-Laurie Pinto
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Véronique Rogemond
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Alberto Vogrig
- Department of Medicine (DMED), University of Udine, Udine, Italy
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Udine, Italy
| | - Bastien Joubert
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
| | - Jérôme Honnorat
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France.
- MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France.
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23
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Vedaei F, Srinivasan D, Parker D, Erus G, Dolui S, Sorond FA, Jacobs DR, Launer LJ, Lackland DT, Davatzikos C, Bryan RN, Nasrallah IM. Spatial and signal features of white matter integrity and associations with clinical factors: A CARDIA brain MRI study. Neuroimage Clin 2025; 46:103768. [PMID: 40101673 PMCID: PMC11964671 DOI: 10.1016/j.nicl.2025.103768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/23/2025] [Accepted: 03/10/2025] [Indexed: 03/20/2025]
Abstract
White matter hyperintensities (WMH) may be indicative of age-related cerebrovascular diseases and contribute to cognitive and functional decline. Normal appearing WM (NAWM) adjacent to WMH, termed "penumbra," is known to be vulnerable to future WMH pathology. WM integrity can be evaluated using multiple magnetic resonance imaging (MRI) modalities. We aimed to identify MRI features predictive of WMH growth and to compare the implications of these features based on spatial proximity to existing WMH versus signal features in baseline NAWM. We used baseline and 5-year follow-up MRI scans in 485 middle-aged participants form the Coronary Artery Risk Development in Young Adults (CARDIA). Multimodal MRI at baseline, including fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging (DTI), and cerebral blood flow (CBF), was measured within WM ROIs including baseline WMH and regions that later developed into new WMH, within and external to the baseline penumbra. Overall, we found that 80% of new WMH appeared within the baseline penumbra. We also found lower fractional anisotropy (FA) and CBF and higher FLAIR and median diffusivity (MD) in NAWM at baseline in regions with subsequent WMH growth compared to those without WMH growth. For NAWM regions defined by signal features, subthreshold FA and suprathreshold MD and FLAIR abnormality at baseline were the most robust predictors of WMH growth. Baseline systolic blood pressure had significant associations with baseline abnormalities in NAWM and subsequently with cognitive decline, particularly for FA and MD measures. The findings support the use of DTI as the predictor of WMH growth, which is correlated with subtle, adverse WM alterations and cognitive function years before developing to WMH. The results may contribute to future clinical trials aimed at preserving WM integrity.
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Affiliation(s)
- Faezeh Vedaei
- AI(2)D, Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
| | - Dhivya Srinivasan
- AI(2)D, Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA
| | - Drew Parker
- Department of Radiology, Diffusion and Connectomics in Precision Healthcare Research Lab, University of Pennsylvania, Philadelphia, PA, USA
| | - Guray Erus
- AI(2)D, Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA
| | - Sudipto Dolui
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Farzaneh A Sorond
- Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - David R Jacobs
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, MN, USA
| | - Lenore J Launer
- Neuroepidemiology Section, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA
| | - Daniel T Lackland
- Division of Translational Neurosciences and Population Studies, Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
| | - Christos Davatzikos
- AI(2)D, Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA
| | - R Nick Bryan
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Ilya M Nasrallah
- AI(2)D, Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
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24
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Becker W, Vintonyak O, Kassubek J. Joint examination of reflexive vertical saccades and small involuntary fixational saccades improves the classification of patients with progressive supranuclear palsy (PSP): a ROC study. Exp Brain Res 2025; 243:90. [PMID: 40080162 PMCID: PMC11906540 DOI: 10.1007/s00221-025-07031-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 02/16/2025] [Indexed: 03/15/2025]
Abstract
A slowing of saccadic eye movements is one of the key symptoms of progressive supranuclear palsy and therefore represents a core functional domain of the current diagnostic criteria. However, there is considerable overlap between the saccade velocities of healthy people and patients in early stages. Therefore, a highly specific discrimination between patients and controls based on eye velocity often results in a considerable loss of sensitivity. Another symptom of progressive supranuclear palsy is a high frequency of square wave jerks formed by small involuntary fixational saccades. Using ROC analyses of 50 patients and 50 controls and focusing on points of 100 and 90% specificity or sensitivity, we investigated whether the velocity and gain data of visually guided reflexive saccades could be combined with each other and with parameters of fixational saccades to improve discriminability compared to considering saccade velocity alone. Both approaches were successful in patients with long disease duration but less so in cases of short duration. The displacement rate produced by square waves during fixation proved helpful because its frequency distributions in patients and controls had value ranges that were not shared by the two groups. This fact allowed an a priori classification of some subjects as either patients or controls. Modified ROC analyses using this a priori information are expected to work equally well in patients with short and long disease duration. In future studies it might be addressed if these methods can also improve the discrimination between PSP and other Parkinsonian disorders.
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Affiliation(s)
- Wolfgang Becker
- Section of Neurophysiology, Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
| | - Olga Vintonyak
- Department of Neurology, University of Ulm, Ulm, Germany
| | - Jan Kassubek
- Section of Neurophysiology, Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany
- Department of Neurology, University of Ulm, Ulm, Germany
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25
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Cottrell TR, Lotze MT, Ali A, Bifulco CB, Capitini CM, Chow LQM, Cillo AR, Collyar D, Cope L, Deutsch JS, Dubrovsky G, Gnjatic S, Goh D, Halabi S, Kohanbash G, Maecker HT, Maleki Vareki S, Mullin S, Seliger B, Taube J, Vos W, Yeong J, Anderson KG, Bruno TC, Chiuzan C, Diaz-Padilla I, Garrett-Mayer E, Glitza Oliva IC, Grandi P, Hill EG, Hobbs BP, Najjar YG, Pettit Nassi P, Simons VH, Subudhi SK, Sullivan RJ, Takimoto CH. Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols. J Immunother Cancer 2025; 13:e010928. [PMID: 40054999 PMCID: PMC11891540 DOI: 10.1136/jitc-2024-010928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 02/05/2025] [Indexed: 03/12/2025] Open
Abstract
Immunotherapy of cancer is now an essential pillar of treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration of new treatment strategies incorporating immune agents in cancer clinical practice. Immunotherapies perturb a complex system of interactions among genomically unstable tumor cells, diverse cells within the tumor microenvironment including the systemic adaptive and innate immune cells. The drive to develop increasingly effective immunotherapy regimens is tempered by the risk of immune-related adverse events. Evidence-based biomarkers that measure the potential for therapeutic response and/or toxicity are critical to guide optimal patient care and contextualize the results of immunotherapy clinical trials. Responding to the lack of guidance on biomarker testing in early-phase immunotherapy clinical trials, we propose a definition and listing of essential biomarkers recommended for inclusion in all such protocols. These recommendations are based on consensus provided by the Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Network (SCION) faculty with input from the SITC Pathology and Biomarker Committees and the Journal for ImmunoTherapy of Cancer readership. A consensus-based selection of essential biomarkers was conducted using a Delphi survey of SCION faculty. Regular updates to these recommendations are planned. The inaugural list of essential biomarkers includes complete blood count with differential to generate a neutrophil-to-lymphocyte ratio or systemic immune-inflammation index, serum lactate dehydrogenase and albumin, programmed death-ligand 1 immunohistochemistry, microsatellite stability assessment, and tumor mutational burden. Inclusion of these biomarkers across early-phase immunotherapy clinical trials will capture variation among trials, provide deeper insight into the novel and established therapies, and support improved patient selection and stratification for later-phase clinical trials.
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Affiliation(s)
- Tricia R Cottrell
- Queen's University Sinclair Cancer Research Institute, Kingston, Ontario, Canada
| | | | - Alaa Ali
- Stem Cell Transplant and Cellular Immunotherapy Program, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, Washington, DC, USA
| | - Carlo B Bifulco
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA
| | - Christian M Capitini
- University of Wisconsin School of Medicine and Public Health and Carbone Cancer Center, Madison, Wisconsin, USA
| | | | - Anthony R Cillo
- UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
- Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Deborah Collyar
- Patient Advocates In Research (PAIR), Danville, California, USA
| | - Leslie Cope
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | | | | | - Sacha Gnjatic
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Denise Goh
- Institute of Molecular and Cell Biology (IMCB), Agency of Science, Technology and Research (A*STAR), Singapore
| | - Susan Halabi
- Duke School of Medicine and Duke Cancer Institute, Durham, North Carolina, USA
| | - Gary Kohanbash
- Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Holden T Maecker
- Stanford University School of Medicine, Stanford, California, USA
| | - Saman Maleki Vareki
- Department of Oncology and Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
| | - Sarah Mullin
- Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Barbara Seliger
- Campus Brandenburg an der Havel, Brandenburg Medical School, Halle, Germany
| | - Janis Taube
- Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Wim Vos
- Radiomics.bio, Liège, Belgium
| | - Joe Yeong
- Institute of Molecular and Cell Biology (IMCB), Agency of Science, Technology and Research (A*STAR), Singapore
- Department of Anatomical Pathology, Singapore General Hospital, Singapore
| | - Kristin G Anderson
- Department of Microbiology, Immunology and Cancer Biology, Department of Obstetrics and Gynecology, Beirne B. Carter Center for Immunology Research and the University of Virginia Comprehensive Cancer Center, University of Virginia, Charlottesville, Virginia, USA
| | - Tullia C Bruno
- UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
- Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - Codruta Chiuzan
- Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
| | | | | | | | | | - Elizabeth G Hill
- Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Brian P Hobbs
- Dell Medical School, The University of Texas, Austin, Texas, USA
| | - Yana G Najjar
- UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | | | | | - Sumit K Subudhi
- The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ryan J Sullivan
- Massachusetts General Hospital, Harvard Medical School, Needham, Massachusetts, USA
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26
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Li G, He X, Yao Q, Dong X. Is the social withdrawal subscale a valid instrument to assess social withdrawal among colorectal cancer survivors with permanent stomas? A validation study. BMC Psychiatry 2025; 25:202. [PMID: 40045225 PMCID: PMC11881444 DOI: 10.1186/s12888-025-06641-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 02/20/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Although social withdrawal is common among colorectal cancer (CRC) survivors with permanent stomas, it has been poorly addressed due to a lack of valid assessment tools. The social withdrawal subscale (SWS) from the Internalized Stigma of Mental Illness (ISMI) scale shows promise for assessing social withdrawal. However, there was no available data on its validity for this purpose. This study aimed to investigate the reliability and validity of the SWS as a screening tool for identifying survivors at risk of social withdrawal. METHODS Two separate convenience samples of 127 and 245 CRC survivors with permanent stomas were selected. Item analysis and exploratory factor analysis (EFA) were conducted with the first sample of 127 survivors. Confirmatory factor analysis (CFA), reliability analysis, and tests for convergent and discriminant validity were performed with the second sample of 245 survivors. Additionally, the screening cut-off score and accuracy of the SWS scores were determined using receiver operating characteristic (ROC) curves. RESULTS The item-total correlation coefficients of the SWS ranged from 0.530 to 0.787. The EFA demonstrated a single-factor structure for the SWS. The CFA confirmed appropriate construct validity (χ²/df = 103.115/52 = 1.983, goodness-of-fit index (GFI) = 0.925, comparative fit index (CFI) = 0.959, and root mean square error of approximation (RMSEA) = 0.068). The test-retest reliability was 0.849. Pearson correlation analysis showed significant and moderate to large relationships between the SWS and the chosen criterion measures, supporting its good convergent validity. ROC analysis identified SWS scores of ≥ 15 as the optimal screening cut-off, with a sensitivity of 86.5%, specificity of 50.5%, and an area under the curve (AUC) of 0.748 (95% CI: 0.673-0.823, P < 0.001). CONCLUSION The SWS demonstrates acceptable reliability and validity for measuring social withdrawal among CRC survivors with permanent stomas. Future studies should further evaluate its utility in clinical settings.
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Affiliation(s)
- Guopeng Li
- School of Nursing and Rehabilitation, Shandong University, 44 Wenhua West Road, Jinan, China
| | - Xudong He
- School of Nursing and Rehabilitation, Shandong University, 44 Wenhua West Road, Jinan, China
| | - Qi Yao
- Colorectal Surgery Ward I, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, P.R. China
| | - Xiaoling Dong
- Colorectal Surgery Ward I, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, P.R. China.
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Klukowska AM, Dol MG, Vandertop WP, Schröder ML, Staartjes VE. Estimating the minimum clinically important difference (MCID) of the five-repetition sit-to-stand test in patients with lumbar disc herniation. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2025; 34:1107-1114. [PMID: 39680122 DOI: 10.1007/s00586-024-08582-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/06/2024] [Accepted: 11/18/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND The impact of surgical interventions on lumbar disc herniation (LDH) is often assessed using objective functional impairment (OFI) tests like the five-repetition sit-to-stand (5R-STS) test. This study calculates the minimum clinically important difference (MCID) for 5R-STS improvement in patients with LDH one year after surgery. METHODS Adult patients with LDH scheduled for surgery were prospectively recruited from a Dutch short-stay spinal clinic. The 5R-STS time, Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ), Numeric Rating Scale for back and leg pain, EQ-5D-3L health-related quality of life questionnaire and EQ5D-VAS were recorded preoperatively, at 6-weeks and 1-year post-operatively. The MCID was calculated using anchor-based methods (within-patient change; between-patient change; and receiver-operating characteristic approaches) and distribution-based methods (0.5 standard deviation (SD); effect size; standard error of measurement; standardized response mean; and 95% minimum detectable change (MDC)). The final MCID value was based on the "gold standard": an averaging of the anchor-based methods using ODI and RMDQ as the closest available anchors. RESULTS We prospectively recruited 134 patients. One-year follow-up was completed by 103 (76.8%) of patients. The MCID values derived using different methods varied from 0.7 to 5.1 s (s). The final, averaged, anchor-based MCID for improvement was 3.6 s. Within distribution-based methods, 95% MDC and 0.5SD approach, yielded an MCID of 3.0 and 3.8 s, respectively, aligning closely with the overall anchor-derived MCID for 5R-STS. CONCLUSION In a patient with LDH, an improvement in 5R-STS performance of at least 3.6 s can be regarded as a clinically relevant improvement.
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Affiliation(s)
- Anita M Klukowska
- Department of Neurosurgery, Bergman Clinics, Amsterdam, The Netherlands
- Amsterdam UMC, Neurosurgery, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Neurosurgery, Medical University of Bialystok, Bialystok, Poland
| | - Manon G Dol
- Department of Neurosurgery, Bergman Clinics, Amsterdam, The Netherlands
| | - W Peter Vandertop
- Amsterdam UMC, Neurosurgery, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Marc L Schröder
- Department of Neurosurgery, Bergman Clinics, Amsterdam, The Netherlands
| | - Victor E Staartjes
- Machine Intelligence in Clinical Neuroscience and Microsurgical Neuroanatomy (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland.
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Siriwong N, Sriphoosanaphan S, Decharatanachart P, Yongpisarn T, Kerr SJ, Treeprasertsuk S, Tiyarattanachai T, Apiparakoon T, Hagström H, Akbari C, Ekstedt M, Yip TCF, Wong GLH, Ito T, Ishigami M, Toyoda H, Peleg N, Shlomai A, Seko Y, Sumida Y, Kawanaka M, Hino K, Chaiteerakij R. Role of noninvasive tests on the prediction of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without cirrhosis: a systematic review and meta-analysis of aggregate and individual patient data. Eur J Gastroenterol Hepatol 2025; 37:358-369. [PMID: 39919008 DOI: 10.1097/meg.0000000000002912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has been identified as an emerging risk factor for hepatocellular carcinoma (HCC). Identifying non-cirrhotic NAFLD patients at risk for HCC is crucial. We aimed to investigate the utility of noninvasive tests (NITs) as predictors for HCC and to determine optimal and cost-effective NIT cutoffs for HCC surveillance in non-cirrhotic NAFLD patients. METHODS Medline, EMBASE, and Scopus databases were searched for studies evaluating the relationship between NITs and HCC in this population. Random-effects models were used to estimate hazard ratios or risk ratios and 95% confidence interval (95% CI). Cutoffs of NITs for identifying high-risk patients for HCC were determined. RESULTS This systematic review comprised 20 studies. A meta-analysis of 379 194 patients was conducted using six studies with individual patient data and five studies with aggregate data. Among NITs studied, fibrosis-4 index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) were significantly associated with HCC, with pooled risk ratio (95% CI) of 9.21 (5.79-14.64), pooled hazard ratio of 12.53 (6.57-23.90), and 13.32 (6.48-27.37), respectively. FIB-4, APRI, and NFS of more than 2.06, 0.65, and 0.51 resulted in the highest area under the receiver operating characteristics of 0.83, 0.80, and 0.85, respectively. Surveillance in patients with FIB-4 ≥ 5.91 and NFS ≥ 2.85 would be cost-effective with an annual HCC incidence of ≥15 per 1000 patient-years. CONCLUSION FIB-4, APRI, and NFS are associated with HCC development in non-cirrhotic NAFLD patients. Different NIT cutoffs may be used to enroll high-risk NAFLD patients for HCC surveillance, according to resource availability in different settings.
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Affiliation(s)
- Nanicha Siriwong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Supachaya Sriphoosanaphan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | | | - Tanat Yongpisarn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Stephen J Kerr
- Biostatistics Excellence Centre, Faculty of Medicine, Chulalongkorn University
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Thodsawit Tiyarattanachai
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Terapap Apiparakoon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet
- Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm
| | | | - Mattias Ekstedt
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics
- Medical Data Analytics Centre
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics
- Medical Data Analytics Centre
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Noam Peleg
- Department of Gastroenterology and Hepatology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva
| | - Amir Shlomai
- Department of Medicine D, Beilinson Hospital, Rabin Medical Center and the Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi
| | - Miwa Kawanaka
- Department of General Internal Medicine, Kawasaki Medical Center, Kawasaki Medical School, Okayama
| | - Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Weisman M, Durm G, Shields MD, Hanna NH, Althouse S, Lautenschlaeger T. Evaluation of Radiation Pneumonitis in a Phase 2 Study of Consolidation Immunotherapy With Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiation Therapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2025; 121:720-727. [PMID: 39490906 DOI: 10.1016/j.ijrobp.2024.09.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 08/26/2024] [Accepted: 09/20/2024] [Indexed: 11/05/2024]
Abstract
PURPOSE The addition of immunotherapy (IO) after concurrent chemoradiation therapy (CCRT) for unresectable non-small cell lung cancer (NSCLC) has become common practice in eligible patients. Approaches to further improve outcomes and reduce treatment-related toxicity for these patients are needed. This study evaluates the risk of radiation pneumonitis after CCRT and its correlation with the radiation dose distribution, IO regimen (nivolumab vs nivolumab plus ipilimumab), and patient demographics across BTCRC-LUN16-081. METHODS AND MATERIALS Patients with unresectable stage III NSCLC after completion of CCRT were enrolled in BTCRC-LUN16-081, a randomized phase 2 trial to assess the efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for 6 months. Radiation dose parameters, patient demographics, and toxicity events were evaluated among treatment arms for risk and severity of pneumonitis. RESULTS One hundred-five patients were enrolled into 2 treatment arms; 54 patients received nivolumab alone, and 51 patients received nivolumab plus ipilimumab. Of these, 104 patients had dose-volume histogram information available. Within this cohort, 65 patients (62.5%) had stage IIIA, and 39 patients (37.5%) had stage IIIB NSCLC disease, per the American Journal Committee on Cancer, seventh edition. During the study, 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. Using logistic regression and evaluating different cutoffs for percentage of normal lung volume receiving at least 20 gy (V20), patients with V20 > 23% demonstrated significantly higher grade 2 or greater pneumonitis rates (37.1% vs 16.2%, P = .031). No significant difference in rates of pneumonitis between arms was identified. Traditional lung dose-volume histogram cutoffs (percentage of normal lung volume receiving at least 5 gy (V5) > 65%, V20 > 35%, and mean > 20 Gy) were not associated with pneumonitis. CONCLUSIONS In patients receiving nivolumab or nivolumab plus ipilimumab after definitive CCRT, lung V20 > 23% was associated with an increased risk of grade 2 or greater pneumonitis. Radiation dose constraints for lungs in patients receiving consolidative IO after CCRT should continue to be evaluated and optimized when feasible.
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Affiliation(s)
- Michael Weisman
- Department of Radiation Oncology, Indiana University School of Medicine
| | - Greg Durm
- Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine
| | - Misty Dawn Shields
- Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine
| | - Nasser H Hanna
- Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine
| | - Sandra Althouse
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana
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Ohyama Y, Kobayashi A, Minoda Y, Iwakiri K, Masuda S, Ohta Y, Sugama R, Nakamura H. Association Between Overhang of the Posterior Femoral Condyle and Restricted Postoperative Knee Flexion Related to Patient-Reported Stiffness in Medial-Pivot Total Knee Arthroplasty. J Arthroplasty 2025; 40:651-657.e2. [PMID: 39265813 DOI: 10.1016/j.arth.2024.08.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 08/28/2024] [Accepted: 08/30/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUND The primary aim of this study was to investigate the association between the posterior longitudinal overhang in the femoral condyle (PLOF) in medial-pivot total knee arthroplasty (TKA) and a change in knee flexion angle (change in flexion). METHODS This retrospective cohort study included 148 knees undergoing medial-pivot TKA for medial knee osteoarthritis. The primary outcome was the change in flexion (c-flexion) preoperatively and 1-year postoperatively. The component positions were evaluated using 3-dimensional measurements, where the PLOF was measured for each medial and lateral femoral condyle. The secondary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index scores taken preoperatively and 2 years postoperatively. A multivariate regression analysis was performed to determine predictors of c-flexion and risk factors for negative c-flexion (less than 0°). Furthermore, a receiver operating characteristic curve was utilized to determine the threshold for negative c-flexion. RESULTS The mean c-flexion was -3.2° ± 8.7, and lateral PLOF was significantly associated with c-flexion (β = -0.52; P < 0.001). Larger preoperative flexion angles (odds ratio, 1.10; P < 0.001) and larger lateral PLOF (odds ratio, 1.69; P = 0.001) were risk factors for negative c-flexion, with thresholds of 129° and 1.1 mm, respectively (sensitivity, 0.79; specificity, 0.72). Additionally, patients who had negative c-flexion (n = 91) demonstrated less improvement in preoperative and 2-year postoperative Western Ontario and McMaster Universities Osteoarthritis Index stiffness subscores than patients who had positive c-flexion (0° or more; n = 57) (P = 0.01). CONCLUSIONS A larger lateral PLOF was associated with decreased and negative c-flexion after medial-pivot TKA. Patients who had negative c-flexion demonstrated less improvement in knee stiffness. Surgical strategies aimed at minimizing lateral PLOF may enhance postoperative knee flexion and overall patient outcomes in medial-pivot TKA.
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Affiliation(s)
- Yohei Ohyama
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan; Department of Orthopaedic Surgery, Shiraniwa Hospital Joint Arthroplasty Center, Nara, Japan
| | - Akio Kobayashi
- Department of Orthopaedic Surgery, Shiraniwa Hospital Joint Arthroplasty Center, Nara, Japan
| | - Yukihide Minoda
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Kentaro Iwakiri
- Department of Orthopaedic Surgery, Shiraniwa Hospital Joint Arthroplasty Center, Nara, Japan
| | - Sho Masuda
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yoichi Ohta
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan; Department of Orthopaedic Surgery, Shiraniwa Hospital Joint Arthroplasty Center, Nara, Japan
| | - Ryo Sugama
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Nakamura
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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Sugawara K, Takaya E, Inamori R, Konaka Y, Sato J, Shiratori Y, Hario F, Kobayashi T, Ueda T, Okamoto Y. Breast cancer classification based on breast tissue structures using the Jigsaw puzzle task in self-supervised learning. Radiol Phys Technol 2025; 18:209-218. [PMID: 39760975 PMCID: PMC11876229 DOI: 10.1007/s12194-024-00874-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 12/18/2024] [Accepted: 12/20/2024] [Indexed: 01/07/2025]
Abstract
Self-supervised learning (SSL) has gained attention in the medical field as a deep learning approach utilizing unlabeled data. The Jigsaw puzzle task in SSL enables models to learn both features of images and the positional relationships within images. In breast cancer diagnosis, radiologists evaluate not only lesion-specific features but also the surrounding breast structures. However, deep learning models that adopt a diagnostic approach similar to human radiologists are still limited. This study aims to evaluate the effectiveness of the Jigsaw puzzle task in characterizing breast tissue structures for breast cancer classification on mammographic images. Using the Chinese Mammography Database (CMMD), we compared four pre-training pipelines: (1) IN-Jig, pre-trained with both the ImageNet classification task and the Jigsaw puzzle task, (2) Scratch-Jig, pre-trained only with the Jigsaw puzzle task, (3) IN, pre-trained only with the ImageNet classification task, and (4) Scratch, that is trained from random initialization without any pre-training tasks. All pipelines were fine-tuned using binary classification to distinguish between the presence or absence of breast cancer. Performance was evaluated based on the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Additionally, detailed analysis was conducted for performance across different radiological findings, breast density, and regions of interest were visualized using gradient-weighted class activation mapping (Grad-CAM). The AUC for the four models were 0.925, 0.921, 0.918, 0.909, respectively. Our results suggest the Jigsaw puzzle task is an effective pre-training method for breast cancer classification, with the potential to enhance diagnostic accuracy with limited data.
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Affiliation(s)
- Keisuke Sugawara
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Eichi Takaya
- Department of Diagnostic Imaging, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
- AI Lab, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
| | - Ryusei Inamori
- Department of Radiological Imaging and Informatics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Yuma Konaka
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Jumpei Sato
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Yuta Shiratori
- Department of Diagnostic Imaging, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Fumihito Hario
- Department of Diagnostic Imaging, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Tomoya Kobayashi
- Department of Diagnostic Imaging, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
- AI Lab, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Takuya Ueda
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Yoshikazu Okamoto
- Department of Diagnostic Imaging, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
- AI Lab, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
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Anisuzzaman D, Malins JG, Jackson JI, Lee E, Naser JA, Rostami B, Greason G, Bird JG, Friedman PA, Oh JK, Pellikka PA, Thaden JJ, Lopez-Jimenez F, Attia ZI, Pislaru SV, Kane GC. Leveraging Comprehensive Echo Data to Power Artificial Intelligence Models for Handheld Cardiac Ultrasound. MAYO CLINIC PROCEEDINGS. DIGITAL HEALTH 2025; 3:100194. [PMID: 40207004 PMCID: PMC11975991 DOI: 10.1016/j.mcpdig.2025.100194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
Objective To develop a fully end-to-end deep learning framework capable of estimating left ventricular ejection fraction (LVEF), estimating patient age, and classifying patient sex from echocardiographic videos, including videos collected using handheld cardiac ultrasound (HCU). Patients and Methods Deep learning models were trained using retrospective transthoracic echocardiography (TTE) data collected in Mayo Clinic Rochester and surrounding Mayo Clinic Health System sites (training: 6432 studies and internal validation: 1369 studies). Models were then evaluated using retrospective TTE data from the 3 Mayo Clinic sites (Rochester, n=1970; Arizona, n=1367; Florida, n=1562) before being applied to a prospective dataset of handheld ultrasound and TTE videos collected from 625 patients. Study data were collected between January 1, 2018 and February 29, 2024. Results Models showed strong performance on the retrospective TTE datasets (LVEF regression: root mean squared error (RMSE)=6.83%, 6.53%, and 6.95% for Rochester, Arizona, and Florida cohorts, respectively; classification of LVEF ≤40% versus LVEF > 40%: area under curve (AUC)=0.962, 0.967, and 0.980 for Rochester, Arizona, and Florida, respectively; age: RMSE=9.44% for Rochester; sex: AUC=0.882 for Rochester), and performed comparably for prospective HCU versus TTE data (LVEF regression: RMSE=6.37% for HCU vs 5.57% for TTE; LVEF classification: AUC=0.974 vs 0.981; age: RMSE=10.35% vs 9.32%; sex: AUC=0.896 vs 0.933). Conclusion Robust TTE datasets can be used to effectively power HCU deep learning models, which in turn demonstrates focused diagnostic images can be obtained with handheld devices.
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Affiliation(s)
- D.M. Anisuzzaman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | | | - John I. Jackson
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Eunjung Lee
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Jwan A. Naser
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Behrouz Rostami
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Grace Greason
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Jared G. Bird
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Paul A. Friedman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Jae K. Oh
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | | | - Jeremy J. Thaden
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | | | - Zachi I. Attia
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Sorin V. Pislaru
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Garvan C. Kane
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
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Xing Z, Xiao M, Schocken DD, Zgibor JC, Alman AC. Sex-specific optimal cut-off points for metabolic health indicators to predict incident type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 2025:103963. [PMID: 40087045 DOI: 10.1016/j.numecd.2025.103963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 02/06/2025] [Accepted: 02/22/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND AND AIM We aimed to determine the optimal cut-off points for metabolic health indicators, including insulin resistance (IR), glucose, insulin, BMI, and waist circumference, in middle-aged nondiabetic people to predict future type 2 diabetes mellitus (T2DM). METHODS AND RESULTS The data came from 12,543 Atherosclerosis Risk Communities Study participants, including 5758 men and 6785 women. They did not have diabetes at baseline and were followed for incident T2DM within 3, 6, and 9 years. IR was estimated using four IR metrics: HOMA-IR, METS-IR, TyG index, and TG/HDL-C. We used the Youden index to determine the optimal cut-off values. In females, the cut-off points for glucose to predict incident T2DM ranged from 96 to 102 mg/dL, with Area Under the Curve (AUC) values of 0.64-0.85. In males, the cut-off points ranged from 102 to 106 mg/dL, with AUC values of 0.60-0.83. For HOMA-IR, the cut-off points in females varied from 2.4 to 3.2, with AUC values of 0.69-0.78, while they ranged from 2.8 to 3.2 in males. The optimal cut-off values for METS-IR, TyG index, TG/HDL-C, insulin, BMI, and waist circumference were 40-43, 8.6-8.9, 2.0-3.2, 9-15 μU/mL, 28-29 kg/m2, and 91-97 cm in women, and 44-45, 8.8-8.9, 2.9-3.2, 11-12 μU/mL, 27-29 kg/m2, and 99-103 cm in men. CONCLUSIONS The optimal threshold for each predictor's prediction of incident T2DM varied by sex. The eight predictors' order of predictive performance were fasting glucose, HOMA-IR, METS-IR, insulin, BMI, waist circumference, TyG index, and TG/HDL-C.
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Affiliation(s)
- Zailing Xing
- College of Public Health, University of South Florida, Tampa, FL, USA
| | - Mianli Xiao
- College of Public Health, University of South Florida, Tampa, FL, USA
| | - Douglas D Schocken
- College of Public Health, University of South Florida, Tampa, FL, USA; School of Medicine, Duke University, Durham, NC, USA
| | - Janice C Zgibor
- College of Public Health, University of South Florida, Tampa, FL, USA
| | - Amy C Alman
- College of Public Health, University of South Florida, Tampa, FL, USA.
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Chunhabundit P, Arayapisit T, Srimaneekarn N. Sex prediction from human tooth dimension by ROC curve analysis: a preliminary study. Sci Rep 2025; 15:6627. [PMID: 39994356 PMCID: PMC11850625 DOI: 10.1038/s41598-025-90801-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 02/17/2025] [Indexed: 02/26/2025] Open
Abstract
Though mathematical approaches are effective in developing reliable odontometric equations with high predictive accuracy for sex estimation in forensic odontology, these methods are often complex to apply, making them impractical in certain scenarios. Consequently, efforts continue to refine these models for greater accessibility. This study aims to develop a sex prediction method based on the horizontal width of anterior teeth using ROC analysis and evaluate its accuracy. Maximum horizontal measurements were taken from all anterior teeth on 100 dental casts from male and 100 from female patients. ROC curve analysis, along with Youden's index and Euclidean index, was used to determine cut-off points for sex estimation. An additional set of 50 male and 50 female dental casts was used to assess the method's accuracy. Results showed that only the canines were statistically significant for sex identification. AUC values were 0.634 and 0.626 for maxillary canines (p = .001) and 0.724 and 0.727 for mandibular canines (p < .001), with accuracy ranging from 69 to 77%. In conclusion, a sex prediction method based on the horizontal width of the canine, using ROC analysis, was developed, demonstrating reasonable accuracy. This methodological improvement is expected to enhance its practical application in forensic investigations.
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Affiliation(s)
- Panjit Chunhabundit
- Department of Anatomy, Faculty of Dentistry, Mahidol University, 6 Yothi Road, Ratchathewi, Bangkok, 10400, Thailand
| | - Tawepong Arayapisit
- Department of Anatomy, Faculty of Dentistry, Mahidol University, 6 Yothi Road, Ratchathewi, Bangkok, 10400, Thailand
| | - Natchalee Srimaneekarn
- Department of Anatomy, Faculty of Dentistry, Mahidol University, 6 Yothi Road, Ratchathewi, Bangkok, 10400, Thailand.
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Yoshinaga M, Ushinohama H, Sato S, Ohno S, Hata T, Horigome H, Tauchi N, Sumitomo N, Nishihara E, Hirono K, Ichida F, Shiraishi H, Nomura Y, Tsukano S, Ninomiya Y, Yoneyma T, Suzuki H, Takahashi H, Ogata H, Makita N, Shimizu W, Horie M, Nagashima M. Screening of 1-Month-Old Infants With Prolonged QT Interval and Its Cutoff Value. Circ J 2025:CJ-24-0148. [PMID: 39993743 DOI: 10.1253/circj.cj-24-0148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
BACKGROUND The prevalence of congenital long QT syndrome (LQTS) (1 : 2,000) is based on genetic testing and ECG data, but the prevalence of electrocardiographically determined prolonged corrected QT interval (pQTc) in infants is unclear. METHODS AND RESULTS Subjects were 10,282 1-month-old infants who participated in 2 prospective ECG screening studies performed in 2010-2011 and 2014-2016. Infants with a QTc ≥0.45 using Bazett's formula [QTc(B)] at 1-month medical checks were re-examined. pQTc was defined as QTc ≥0.46 on 2 different ECGs in early infancy. Infants with QTc ≥0.50 or progressive prolongation of QTc to 0.50 were defined as at high risk. The prevalence of infants with a pQTc was 11/10,282 (1 : 935; 95% confidence interval, 1 : 588-1 : 2,283). Five infants were diagnosed as at high risk, and all infants had an abrupt increase in QTc(B) values in early infancy, mostly at 6-11 weeks after birth and when medication was started. No infants with a pQTc experienced LQTS-related symptoms. Statistical analysis showed that a cutoff QTc(B) ≥0.45 was optimal for screening infants with a pQTc. CONCLUSIONS The prevalence of ECG-determined pQTc is approximately 1 : 1,000. An abrupt increase in QTc(B) values occurs in infants at high risk, mostly at 6-11 weeks after birth. A cutoff QTc(B) value ≥0.45 may be appropriate for 1-month-old screening in this population.
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Affiliation(s)
- Masao Yoshinaga
- Department of Pediatrics, NHO Kagoshima Medical Center
- Orange Medical and Welfare Center for Severe Motor and Intellectual Disabilities
| | | | - Seiichi Sato
- Division of Pediatric Cardiology & Pediatric Intensive Care Unit, Okinawa Prefectural Nanbu Medical Center & Children's Medical Center
| | - Seiko Ohno
- Medical Genome Center, National Cerebral and Cardiovascular Center
| | - Tadayoshi Hata
- Fujita Health University, Graduate School of Health Science
| | - Hitoshi Horigome
- Department of Child Health, Graduate School of Comprehensive Human Sciences, University of Tsukuba
| | | | - Naokata Sumitomo
- Department of Pediatric Cardiology, Saitama Medical University International Medical Center
| | - Eiki Nishihara
- Pediatric Cardiology and Neonatology, Ogaki Municipal Hospital
| | - Keiichi Hirono
- Department of Pediatrics, Toyama University Graduate School of Medicine
| | | | | | | | | | | | | | - Hiroshi Suzuki
- Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital
| | - Hideto Takahashi
- Graduate School of Environmental Information, Teikyo Heisei University
| | | | - Naomasa Makita
- Omics Research Center, National Cerebral and Cardiovascular Center
- Department of Cardiology, Sapporo Teishinkai Hospital
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Minoru Horie
- Department of Cardiovascular Medicine, Shiga University of Medical Science
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Alagic Z, Duran CV, Svensson-Marcial A, Koskinen SK. Contrast-enhanced photon-counting detector CT for discriminating local recurrence from postoperative changes after resection of pancreatic ductal adenocarcinoma. Eur Radiol Exp 2025; 9:26. [PMID: 39985649 PMCID: PMC11846822 DOI: 10.1186/s41747-025-00567-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 01/30/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND We evaluated the diagnostic capability of photon-counting detector computed tomography (PCD-CT) spectral variables in late arterial phase (LAP) and portal venous phase (PVP) to discriminate between local tumor recurrence (LTR) and postoperative changes (POC) after pancreatic ductal adenocarcinoma (PDAC) resection. METHODS Seventy-three consecutive PCD-CT scans in 73 patients with postoperative soft-tissue lesions (PSLs) were included, 42 with POC and 31 with LTR. Regions of interest were drawn in each PSL, and spectral variables were calculated: iodine concentration (IC), normalized IC (NIC), fat fraction, attenuation at 40, 70, and 90 keV, and slope of the spectral curve between 40-90 keV. Multivariable binary logistic regression models were constructed. Diagnostic performance was assessed for LAP and PVP using receiver operating characteristic analysis. RESULTS In LAP, all variables except fat fraction showed significant differences between LTR and POC (p ≤ 0.025). In PVP, all variables except NIC and fat fraction demonstrated significant differences between LTR and POC (p ≤ 0.005). Logistic regression analysis included NIC and 70 keV in the LAP-based model and IC and 90 keV in the PVP-based model. Both models achieved a higher area under the curve (AUC) than individual spectral variables in each phase. The LAP-based model achieved an AUC of 0.919 with 94% sensitivity, 84% specificity, and 87% accuracy, while the PVP-based model reached 0.820, 71%, 88%, and 81%, respectively. CONCLUSION Spectral variables from PCD-CT help distinguish between LTR and POC in LAP and PVP post-PDAC resection. Multivariable logistic regression improves diagnostic performance, especially in LAP. RELEVANCE STATEMENT Measuring normalized iodine concentration and attenuation at 70 keV in late arterial phase, or iodine concentration and attenuation at 90 keV in portal venous phase, and incorporating these values into a logistic regression model can help differentiate between local tumor recurrence and postoperative changes after pancreatic ductal adenocarcinoma resection. KEY POINTS Distinguishing recurrence from postoperative changes on CT after pancreatic ductal adenocarcinoma resection is challenging. PCD-CT spectral variable values differed significantly between local tumor recurrence (LTR) and postoperative changes (POC). Logistic regression of spectral variables can help distinguish LTR from POC. The late arterial phase-based model reached an AUC of 0.919 with 94% sensitivity and 84% specificity.
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Affiliation(s)
- Zlatan Alagic
- Department of Diagnostic Radiology, Karolinska University Hospital, 171 76, Stockholm, Sweden.
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 171 77, Stockholm, Sweden.
| | - Carlos Valls Duran
- Department of Diagnostic Radiology, Karolinska University Hospital, 171 76, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 171 77, Stockholm, Sweden
| | - Anders Svensson-Marcial
- Department of Diagnostic Radiology, Karolinska University Hospital, 171 76, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 171 77, Stockholm, Sweden
| | - Seppo K Koskinen
- Department of Diagnostic Radiology, Karolinska University Hospital, 171 76, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 171 77, Stockholm, Sweden
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Karaca M, Kalyoncuoğlu M, Zengin A, Eren S, Keskin K, Oflar E, Karataş MB, Çalık AN. The Prognostic Value of the Advanced Lung Cancer Inflammation Index for Major Cardiovascular and Cerebrovascular Events in Patients with Non-ST Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention. J Clin Med 2025; 14:1403. [PMID: 40094797 PMCID: PMC11899939 DOI: 10.3390/jcm14051403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 01/29/2025] [Accepted: 02/18/2025] [Indexed: 03/19/2025] Open
Abstract
Objectives: Our aim was to investigate whether admission advanced lung cancer inflammation index (ALI) values have a prognostic role on one-year major adverse cardiovascular and cerebrovascular events (MACCEs) in non-ST elevation myocardial infarction (NSTEMI) patients undergoing percutaneous coronary intervention (PCI). Methods: Our study consisted of 1173 consecutive patients aged 61.9 ± 12.5 years. The study population was divided into two groups according to the occurrence of MACCEs. BMI (body mass index), serum albumin levels and NLR (neutrophil to lymphocyte ratio) of patients were collected from hospital records, and ALI was calculated based on the following formula: BMI × serum albumin/NLR. We also calculated neutrophil to lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR) and uric acid to albumin ratio (UAR) and investigated the association of these inflammation-based biomarkers with one-year MACCEs. Results: During the 12-month follow-up period, 158 (13.5%) patients had MACCEs, 55 (4.7%) of whom had all-cause mortality, 96 (8.2%) had nonfatal MI and 7 (0.6%) had nonfatal stroke. Patients with MACCEs had significantly lower ALI (p < 0.001), and also ALI (area under the curve [AUC] = 0.658, p < 0.001) had better discriminatory power and predictive accuracy in determining one-year MACCEs compared to albumin (AUC = 0.594, p < 0.001), NLR (AUC = 0.631, p < 0.001), CAR (AUC = 0.595, p < 0.001) and UAR (AUC = 0.577, p = 0.001) in the ROC analysis. Individuals with an ALI value lower than 43.9 were at greater risk of developing MACCEs (p < 0.001) due to the Delong test. Conclusions: Determining the level of ALI may have the potential to improve risk prognostication in NSTEMI patients undergoing revascularization therapy.
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Affiliation(s)
- Mehmet Karaca
- Cardiology Department, Atasehir Memorial Hospital, Uskudar University, Istanbul 34662, Turkey;
| | - Muhsin Kalyoncuoğlu
- Bakırköy Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul 34758, Turkey;
| | - Ahmet Zengin
- Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Education Research Hospital, University of Health Sciences, Istanbul 34668, Turkey; (A.Z.); (S.E.); (K.K.); (M.B.K.); (A.N.Ç.)
| | - Semih Eren
- Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Education Research Hospital, University of Health Sciences, Istanbul 34668, Turkey; (A.Z.); (S.E.); (K.K.); (M.B.K.); (A.N.Ç.)
| | - Kıvanç Keskin
- Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Education Research Hospital, University of Health Sciences, Istanbul 34668, Turkey; (A.Z.); (S.E.); (K.K.); (M.B.K.); (A.N.Ç.)
| | - Ersan Oflar
- Bakırköy Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul 34758, Turkey;
| | - Mehmet Baran Karataş
- Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Education Research Hospital, University of Health Sciences, Istanbul 34668, Turkey; (A.Z.); (S.E.); (K.K.); (M.B.K.); (A.N.Ç.)
| | - Ali Nazmi Çalık
- Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Education Research Hospital, University of Health Sciences, Istanbul 34668, Turkey; (A.Z.); (S.E.); (K.K.); (M.B.K.); (A.N.Ç.)
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Lee SY, Lee YJ, Chiu CK, Chandirasegaran S, Hasan MS, Chan CYW, Kwan MK. Analysis of Clinical and Radiological Predictive Factors for Moderate and Severe Pulmonary Impairment in 102 Adolescent Idiopathic Scoliosis (AIS) Patients With Major Cobb Angle ≥45°: A Study of an Asian Population. Global Spine J 2025:21925682251321480. [PMID: 39960040 PMCID: PMC11833796 DOI: 10.1177/21925682251321480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/20/2025] Open
Abstract
STUDY DESIGN Retrospective cohort study. OBJECTIVE To investigate the independent predictive factors for moderate-severe pulmonary impairment (MSPI) among adolescent idiopathic scoliosis (AIS) patients. METHODS The preoperative pulmonary function tests (PFTs) of 102 AIS patients (major Cobb angle ≥45°) operated between 2015 and 2020 were retrospectively reviewed. Patients were divided into 2 groups based on the predicted forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), respectively. Group 1 had normal/ mild pulmonary impairment (FVC or FEV1 >65% predicted) whereas Group 2 had MSPI (FVC or FEV1 ≤65% predicted). Multivariate logistic regression analysis was performed to determine the predictive factors for MSPI. RESULTS 41.2% (N = 42) and 52.0% (N = 53) of the total patients were categorised into Group 2 (MSPI) based on predicted FVC and FEV1, respectively. In general, Group 2 had more patients with a major main thoracic (MT) curve, larger MT curve with lower MT flexibility, a larger MT apical vertebra translation (MT-AVT), and a smaller thoracolumbar-lumbar (TL/L) AVT than Group 1 (P < .05). When analyzing the MT Cobb angle for every 10° increment, patients with MT Cobb angle ≥70° had MSPI (N = 31.4%). Body mass index (BMI) (FVC: aOR .8; FEV1: aOR .9) and MT Cobb angle (for every 10° increment, FVC: aOR 1.7; FEV1: aOR 1.8) were the significant independent predictive factors for MSPI. CONCLUSION MSPI was evident in patients with MT Cobb angle ≥70°, with MT Cobb angle and BMI being the significant independent predictive factors.
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Affiliation(s)
- Sin Ying Lee
- Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Yu Jie Lee
- Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Chee Kidd Chiu
- Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Saturveithan Chandirasegaran
- Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Mohd Shahnaz Hasan
- Department of Anesthesiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Chris Yin Wei Chan
- Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Mun Keong Kwan
- Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
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Shimada H, Doi T, Tsutsumimoto K, Makino K, Harada K, Tomida K, Morikawa M, Makizako H. A New Computer-Based Cognitive Measure for Early Detection of Dementia Risk (Japan Cognitive Function Test): Validation Study. J Med Internet Res 2025; 27:e59015. [PMID: 39951718 PMCID: PMC11888094 DOI: 10.2196/59015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 09/25/2024] [Accepted: 11/28/2024] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND The emergence of disease-modifying treatment options for Alzheimer disease is creating a paradigm shift in strategies to identify patients with mild symptoms in primary care settings. Systematic reviews on digital cognitive tests reported that most showed diagnostic performance comparable with that of paper-and-pencil tests for mild cognitive impairment and dementia. However, most studies have small sample sizes, with fewer than 100 individuals, and are based on case-control or cross-sectional designs. OBJECTIVE This study aimed to examine the predictive validity of the Japanese Cognitive Function Test (J-Cog), a new computerized cognitive battery test, for dementia development. METHODS We randomly assigned 2520 older adults (average age 72.7, SD 6.7 years) to derivation and validation groups to determine and validate cutoff points for the onset of dementia. The Mini-Mental State Examination (MMSE) was used for comparison purposes. The J-Cog consists of 12 tasks that assess orientation, designation, attention and calculation, mental rotation, verbal fluency, sentence completion, working memory, logical reasoning, attention, common knowledge, word memory recall, and episodic memory recall. The onset of dementia was monitored for 60 months. In the derivation group, receiver operating characteristic curves were plotted to determine the MMSE and J-Cog cutoff points that best discriminated between the groups with and without dementia. In the validation group, Cox proportional regression models were developed to predict the associations of the group classified using the cutoff points of the J-Cog or MMSE with dementia incidence. Harrell C-statistic was estimated to summarize how well a predicted risk score described an observed sequence of events. The Akaike information criterion was calculated for relative goodness of fit, where lower absolute values indicate a better model fit. RESULTS Significant hazard ratios (HRs) for dementia incidence were found using the MMSE cutoff between 23 and 24 point (HR 1.93, 95% CI 1.13-3.27) and the J-Cog cutoff between 43 and 44 points (HR 2.42, 95% CI 1.50-3.93). In the total validation group, the C-statistic was above 0.8 for all cutoff points. Akaike information criterion with MMSE cutoff between 23 and 24 points as a reference showed a poor fit for MMSE cutoff between 28 and 29 points, and a good fit for the J-Cog cutoff between 43 and 44 points. CONCLUSIONS The J-Cog has higher accuracy in predicting the development of dementia than the MMSE and has advantages for use in the community as a test of cognitive function, which can be administered by nonprofessionals.
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Affiliation(s)
- Hiroyuki Shimada
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Takehiko Doi
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Kota Tsutsumimoto
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Keitaro Makino
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Kenji Harada
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Kouki Tomida
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Masanori Morikawa
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
| | - Hyuma Makizako
- Department of Preventive Gerontology, Centre for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Ōbu, Japan
- Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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Bahadoran Z, Ghafouri-Taleghani F, Azizi F, Ghasemi A. High Serum Zinc Concentration Accelerates Progression of Isolated Impaired Glucose Tolerance to Type 2 Diabetes: A Cohort Study. Biol Trace Elem Res 2025:10.1007/s12011-025-04545-w. [PMID: 39939554 DOI: 10.1007/s12011-025-04545-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Accepted: 02/04/2025] [Indexed: 02/14/2025]
Abstract
This cohort study investigated the possible association between serum zinc (SZn) concentration and the risk of progression to type 2 diabetes (T2D) in subjects with isolated impaired glucose tolerance (iIGT). SZn was measured in 198 subjects with iIGT (mean age: 53.0 ± 14.4 years and 33.8% were men) at baseline (2009-2011), and they were followed for developing T2D up to 2017. A univariate unrestricted regression spline (UVRS) was used to assess the potential non-linear association and identify the best placement of SZn knots related to the incidence of T2D. Multivariable Cox proportional hazard models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of incident T2D across the best placement of knots. The predictive power of SZn for developing T2D was determined using receiver operating characteristic (ROC) analyses, and the Youden index identified the optimal cut-off values. Mean baseline SZn concentration was 115 ± 42.9 µg/dL. Over a median 6-year follow-up, 27.8% of subjects with iIGT developed T2D. A non-linear association was observed between SZn and the incidence of T2D (pnon-linearity from the likelihood ratio test < 0.001). Higher SZn ≥ 106 µg/dL and ≥ 134 µg/dL was associated with elevated risk of T2D by 127% (HR = 2.27, 95% CI = 1.01-5.10) and 144% (HR = 2.44, 95% CI = 1.05-5.69), respectively. According to the crude and multivariate-adjusted ROC analyses, the optimal cut-off values of SZn to identify incident T2D were ≥ 87.5 µg/dL (sensitivity of 83.6%, specificity of 30.1%) and 151.8 µg/dL (sensitivity of 64.4%, specificity of 76.3%), respectively. Elevated SZn levels at baseline were positively associated with the future risk of T2D in subjects with iIGT.
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Affiliation(s)
- Zahra Bahadoran
- Micronutrient Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fateme Ghafouri-Taleghani
- Micronutrient Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St., Yemen St., Chamran Exp., P.O. Box, Tehran, 19395-4763, Iran.
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Llamas-Amor E, Ortín-Bustillo A, López-Martínez MJ, Muñoz-Prieto A, Manzanilla EG, Arense J, Miralles-Chorro A, Fuentes P, Martínez-Subiela S, González-Bulnes A, Goyena E, Martínez-Martínez A, Cerón JJ, Tecles F. Use of Saliva Analytes as a Predictive Model to Detect Diseases in the Pig: A Pilot Study. Metabolites 2025; 15:130. [PMID: 39997755 PMCID: PMC11857661 DOI: 10.3390/metabo15020130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/10/2025] [Accepted: 02/11/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND/OBJECTIVES Saliva is gaining importance as a diagnostic sample in pigs. The aim of this research was to evaluate a panel of salivary analytes in three porcine diseases and establish predictive models to detect them. METHODS Saliva samples were obtained from healthy pigs (n = 97) and pigs affected by meningitis due to Streptococcus suis (n = 118), diarrhea due to enterotoxigenic Escherichia coli (ETEC, n = 77), and porcine reproductive and respiratory syndrome (PRRS, n = 52). The following biomarkers were analyzed: adenosine deaminase (ADA), haptoglobin (Hp), calprotectin (Calp), aldolase, alpha-amylase (sAA), lactate dehydrogenase (LDH), total protein (TP), and advanced oxidation protein products (AOPPs). Predictive models based on binary logistic regression and decision trees combining those analytes for detecting specific diseases were constructed. RESULTS The results showed a different biomarker profile between the groups. S. suis and ETEC pigs showed higher values of ADA, Hp, Calp, aldolase, sAA, LDH, and TP than healthy pigs. Pigs with PRRS showed higher values of Hp, Calp, sAA, and LDH than healthy animals. The constructed predictive models showed overall accuracies of over 78% and 87% for differentiating ETEC and PRRS, respectively, whereas the models did not accurately predict S. suis infection. CONCLUSIONS Salivary analytes show different changes in pigs depending on the disease, and the combination of these analytes can contribute to the prediction of different diseases. Further studies should be conducted in larger populations to confirm these findings and evaluate their possible practical applications.
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Affiliation(s)
- Eva Llamas-Amor
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
| | - Alba Ortín-Bustillo
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
| | - María José López-Martínez
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
| | - Alberto Muñoz-Prieto
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
| | - Edgar García Manzanilla
- Pig Development Department, Moorepark Animal and Grassland Research Centre, Teagasc, Irish Agriculture and Food Development Authority, P61 C996 Cork, Ireland;
- School of Veterinary Medicine, University College Dublin, D04 W6F6 Dublin, Ireland
| | - Julián Arense
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120 Murcia, Spain;
| | - Aida Miralles-Chorro
- Anatomy and Compared Pathology Anatomy Department, Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain;
- Cátedra Universitaria Grupo Fuertes, 30100 Murcia, Spain;
| | - Pablo Fuentes
- Cátedra Universitaria Grupo Fuertes, 30100 Murcia, Spain;
| | - Silvia Martínez-Subiela
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
| | - Antonio González-Bulnes
- Departamento de Producción y Sanidad Animal, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, C/Tirant lo Blanc, 7, 46115 Valencia, Spain;
- Cuarte S.L. Grupo Jorge, Ctra. De Logroño, Km 9.2, 50120 Zaragoza, Spain
| | - Elena Goyena
- Animal Health Department, Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain;
| | | | - José Joaquín Cerón
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
| | - Fernando Tecles
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain; (E.L.-A.); (A.O.-B.); (M.J.L.-M.); (A.M.-P.); (S.M.-S.); (J.J.C.)
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Wollmann L, Hauser L, van der Feltz-Cornelis C, Mengue SS, Roman R, Rech MRA, Harzheim E. Defining quality categories for evaluation of the doctor-patient relationship assessed through the patient-doctor relationship questionnaire (PDRQ-9). Fam Pract 2025; 42:cmae068. [PMID: 39603262 DOI: 10.1093/fampra/cmae068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The quality of the doctor-patient relationship plays a crucial role in patients' experiences with healthcare services, positively influencing clinical outcomes and satisfaction with care. The Patient-Doctor Relationship Questionnaire (PDRQ-9) is widely used to assess this relationship. However, there are no quality categories that can be derived from the instrument's score to facilitate understanding and decision-making. OBJECTIVES This study aims to establish categories of the quality of the relationship based on the PDRQ-9 score. METHODS A latent class analysis (LCA) was conducted using interviews with 6160 users of primary health care units throughout Brazil to define different homogeneous response profiles. The Youden index was used to determine the cut point between classes. RESULTS LCA identified the presence of two response profiles, one associated with a high evaluation of the quality of the doctor-patient relationship and another associated with a moderate evaluation. The cut point between classes, established through the Youden index, was 3.5 (on a possible score range of 1-5) or 31 (on a possible score range of 9-45). The cut point demonstrated high accuracy (0.94), sensitivity (0.96), and specificity (0.98). CONCLUSIONS The categorization proposed in this study enhances the interpretability of PDRQ-9 results, providing a practical framework for assessing the quality of the doctor-patient relationship. By establishing actionable quality categories, this tool could support targeted interventions, such as performance feedback and training, aimed at fostering empathy, communication, and trust in healthcare settings.
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Affiliation(s)
- Lucas Wollmann
- Conceição Hospital Group, Primary Health Care Management, Av. Francisco Trein, 596, Porto Alegre, 91350200, Brazil
| | - Lisiane Hauser
- School of Medicine, Department of Social Medicine, Federal University of Rio Grande do Sul, R. Ramiro Barcelos, 2400, Porto Alegre, 90035003, Brazil
| | | | - Sotero Serrate Mengue
- School of Medicine, Department of Social Medicine, Federal University of Rio Grande do Sul, R. Ramiro Barcelos, 2400, Porto Alegre, 90035003, Brazil
| | - Rudi Roman
- School of Medicine, Department of Social Medicine, Federal University of Rio Grande do Sul, R. Ramiro Barcelos, 2400, Porto Alegre, 90035003, Brazil
| | | | - Erno Harzheim
- School of Medicine, Department of Social Medicine, Federal University of Rio Grande do Sul, R. Ramiro Barcelos, 2400, Porto Alegre, 90035003, Brazil
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Gökçe E, Freret T, Langeard A. Blood Biomarker Signatures for Slow Gait Speed in Older Adults: An Explainable Machine Learning Approach. Brain Behav Immun 2025; 124:295-304. [PMID: 39674557 DOI: 10.1016/j.bbi.2024.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 12/05/2024] [Accepted: 12/09/2024] [Indexed: 12/16/2024] Open
Abstract
Maintaining physical function is crucial for independent living in older adults, with gait speed being a key predictor of health outcomes. Blood biomarkers may potentially monitor older adults' mobility, yet their association with slow gait speed still needs to be explored. This study aimed to investigate the relationship between blood biomarkers and gait speed using the Midlife in the United States (MIDUS) study biomarker dataset. A cross-sectional design was employed for analysis, involving 405 individuals aged 60 years and over. We used a machine learning framework, specifically the XGBoost algorithm, feature selection methods, and the Shapley Additive Explanations, to develop an explainable prediction model for slow gait speed. Our model demonstrated the highest cross-validation score with the six most important features among 35 variables, as elevated interleukin-6, C-reactive protein, glycosylated hemoglobin, interleukin-8, older age, and female sex were significantly associated with reduced gait speed (area under the curve = 0.75). Our findings suggest that blood biomarkers can play a critical role in integrated models to assess and monitor slow gait speed in older adults. Identifying key blood biomarkers provides valuable insights into the underlying physiological mechanisms of mobility decline and offers promising avenues for early intervention to preserve mobility in the aging population.
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Affiliation(s)
- Evrim Gökçe
- Université de Caen Normandie, INSERM, CYCERON, COMETE UMR 1075, Caen, France.
| | - Thomas Freret
- Université de Caen Normandie, INSERM, CYCERON, COMETE UMR 1075, Caen, France
| | - Antoine Langeard
- Université de Caen Normandie, INSERM, CYCERON, COMETE UMR 1075, Caen, France
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Santos C, Maia H, Pitanga F, de Almeida M, da Fonseca M, de Aquino E, Cardoso L, Griep R, Barreto S, Suemoto C, Lotufo P, Bensenor I, de Matos S. Hand Grip Strength Cut-Off Points as a Discriminator of Sarcopenia and Sarcopenic Obesity: Results from the ELSA-Brasil Cohort. J Cachexia Sarcopenia Muscle 2025; 16:e13723. [PMID: 39966694 PMCID: PMC11835543 DOI: 10.1002/jcsm.13723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/26/2024] [Accepted: 12/08/2024] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Hand grip strength (HGS) may represent an epidemiologically relevant alternative as an initial screening tool for sarcopenia and sarcopenic obesity. However, no study evaluated the performance capacity of HGS compared to other biomarkers in discriminating these conditions in adults. OBJECTIVE The study aimed to evaluate the performance of HGS as discriminator of sarcopenia and sarcopenic obesity, compared to urinary biomarkers of creatinine and potassium in 24 h for Brazilian adults. METHODS Cross-sectional study. Women (n = 5431) and men (n = 6351) aged 38-79 years who participated in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) at second follow-up of the cohort (2012-2014). The area under the receiver operating characteristic curve (AUC) and the respective 95% confidence intervals were calculated for men and women in different age groups to assess the performance of HGS as a discriminator of sarcopenia and sarcopenic obesity, compared to the biomarkers of potassium and creatinine in urine in 24 h. The outcomes were classified based on the skeletal muscle mass index (BMI/height2) and fat percentage, estimated from the bioimpedance analysis data. Sensitivity, specificity and Brier score were calculated for each estimated HGS cut-off point. RESULTS It can be observed that 18.20% (15.51% women; 21.34% men) of the population showed a decline in skeletal muscle mass (sarcopenia). Of this total, 11.61% (10.52% women; 12.89% men) presented the isolated outcome of sarcopenia and 6.59% (4.99% women; 8.45% men) of sarcopenic obesity. The HGS areas under the ROC Curve ranged from 0.54 (CI = 0.493-0.596) to 0.76 (CI = 0.650-0.878) according to sex and age group. HGS performance compared to biomarkers was significantly higher in virtually all strata and outcomes analysed. The cut-off points that demonstrated greater accuracy and better performance in outcome discrimination were ≤ 42, ≤ 41, ≤ 38 and ≤ 36 kgf among males aged 38-44 years, 45-54 years, 55-64 years and 65-79 years, respectively. For women in the same age groups, HGS cut-offs were ≤ 26, ≤ 23, ≤ 23 and ≤ 21 kgf, respectively. CONCLUSIONS The results suggest that HGS is a good discriminator of sarcopenia and sarcopenic obesity, capable of achieving superior or equal performance to muscle mass biomarkers, especially in middle-aged adults.
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Grants
- Brazilian Ministry of Health
- 01 06 0010.00 Brazilian Ministry of Science, Technology and Innovation
- and 01.10.0643.03 Brazilian Ministry of Science, Technology and Innovation
- 01 06 0212.00 Brazilian Ministry of Science, Technology and Innovation
- 01.10.0742-00 Brazilian Ministry of Science, Technology and Innovation
- 01 06 0300.00 Brazilian Ministry of Science, Technology and Innovation
- 01.12.0284.00 Brazilian Ministry of Science, Technology and Innovation
- 01 06 0278.00 Brazilian Ministry of Science, Technology and Innovation
- 01 10 0746 00 Brazilian Ministry of Science, Technology and Innovation
- 01 06 0115.00 Brazilian Ministry of Science, Technology and Innovation
- 01.10.0773-00 Brazilian Ministry of Science, Technology and Innovation
- 01 06 0071. Brazilian Ministry of Science, Technology and Innovation
- 01.11.0093.01 Brazilian Ministry of Science, Technology and Innovation
- Brazilian Ministry of Health
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Affiliation(s)
- Clarice Alves Santos
- Department of Biological SciencesState University of the Southwest of BahiaJequiéBahiaBrazil
| | - Helena Fraga Maia
- Department of Life SciencesState University of BahiaSalvadorBahiaBrazil
| | | | | | | | | | | | - Rosane Harter Griep
- Laboratory of Health and Environment EducationOswaldo Cruz InstituteRio de JaneiroBrazil
| | - Sandhi Maria Barreto
- Faculty of Medicine & Clinical HospitalFederal University of Minas GeraisBelo HorizonteMinas GeraisBrazil
| | - Claudia Kimie Suemoto
- Division of GeriatricsUniversity of São Paulo, Faculdade de MedicinaSão PauloBrazil
- Center for Clinical and Epidemiological ResearchUniversity of São PauloSão PauloBrazil
| | - Paulo Lotufo
- Center for Clinical and Epidemiological ResearchUniversity of São PauloSão PauloBrazil
| | - Isabela Bensenor
- Center for Clinical and Epidemiological ResearchUniversity of São PauloSão PauloBrazil
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Kalyoncuoglu M, Gumusdag A, Oguz H, Ogur H, Ozturk S, Karabulut D. Newly defined biomarker for the no reflow phenomenon in patients with non-ST elevation acute coronary syndrome; uric acid to creatinine ratio. Acta Cardiol 2025; 80:61-69. [PMID: 39817580 DOI: 10.1080/00015385.2025.2452101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 09/29/2024] [Accepted: 01/03/2025] [Indexed: 01/18/2025]
Abstract
BACKGROUND The present study aimed to investigate whether newly defined serum uric acid (SUA) to serum creatinine ratio (SUA/SCr) predicts no-reflow phenomenon (NRP) development in patients with non-ST-elevated acute coronary syndrome (NSTE-ACS). METHODS The study group was divided into two groups: those who developed NRP and those who did not. Complete blood counts, SUA, serum creatinine, C-reactive protein (CRP) and albumin were obtained at admission. The SUA/SCr, SUA to albumin ratio (UAR), C-reactive protein to albumin ratio (CAR) and systemic immune inflammation (SII) index values of all patients were calculated and their relationships with NRP were evaluated. RESULTS Patients with NRP had higher mean SUA/SCr ratio (7.19 ± 2.14 vs 5.30 ± 1.70, p < 0.001), mean UAR (1.73 ± 0.69 vs 1.38 ± 0.47, p < 0.001), median CAR (1.73 vs 1.54, p = 0.002), and median SII index (861.9 vs 730.9, p = 0.015) levels than in those who did not develop NRP. According to multivariant analysis models, SUA/SCr ratio, UAR, CAR and SII index were found to be independent predictors of NRP development (p < 0.05 for all) but only the area under the curve (AUC) for SUA/SCr ratio (AUC = 0.73, p < 0.001) was above the 0.70 proficiency level, performing markedly better than the other evaluated parameters. A SUA/SCr ratio ≥5.34 predicted the NRP with 75% sensitivity and 55% specificity. CONCLUSION SUA/SCr ratio can be used as a reliable marker in prediction the development of NRP in NSTE-ACS patients.
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Affiliation(s)
- Muhsin Kalyoncuoglu
- Cardiology Department, Haseki Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Ayca Gumusdag
- Cardiology Department, Haseki Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Huseyin Oguz
- Cardiology Department, Haseki Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Hasan Ogur
- Cardiology Department, Haseki Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Semi Ozturk
- Cardiology Department, Bakırköy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Dilay Karabulut
- Cardiology Department, Bakırköy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
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Kusano S, Miyata K, Yoshikawa K, Mizukami M. Construct validity, responsiveness, and interpretability of the Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI). J Spinal Cord Med 2025:1-13. [PMID: 39817851 DOI: 10.1080/10790268.2024.2448039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2025] Open
Abstract
OBJECTIVE We investigated the construct validity, responsiveness, and interpretability of the Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI) to determine its usefulness in measuring the functional level of gait. PATIENTS AND METHODS This was a prospective observational study following the checklist of the Consensus-Based Standards for Selecting Health Measurement Instruments. The SCI-FAI consists of three items: Gait Parameter, Assistive Devices, and Temporal. We recruited 55 patients diagnosed with a spinal cord injury (SCI) in the subacute or chronic phase from Ibaraki Prefectural University of Health Sciences Hospital. Construct validity was clarified by hypothesis testing and the rate of hypothesis verification. We divided responsiveness into subacute and chronic groups and determined the correlation between the changes in the two timepoints of the SCI-FAI and 6-minute walk test. Interpretability involved the calculation of cutoff values for indoor and outdoor walking. RESULTS Construct validity was confirmed for 12 of the 15 hypotheses, indicating high construct validity. In the subacute group, Gait Parameter and Assistive Devices showed moderate responsiveness. Interpretability showed that the Gait Parameter was perfect in 19 of the 20 subjects who did not need a walking aid when walking. The cutoff value for Gait Parameter for indoor walking was 17.5 points (AUC 0.91) and that for Assistive Devices was 9.5 points (AUC 0.88). The cutoff values for outdoor walking were Gait Parameter 18.5 points (AUC 0.96) and Assistive Devices 10.5 points (AUC 0.94). CONCLUSION Our results demonstrated that the SCI-FAI has adequate construct validity, moderate responsiveness in SCI patients in the subacute phase, and interpretability in the gait assessment of individuals with SCIs. Gait Parameter is likely to show a ceiling effect for people with SCIs who can walk without using an upper-limb walking aid.
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Affiliation(s)
- Shinogu Kusano
- Graduate School of Health Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan
- Ibaraki Prefectural University of Health Sciences Hospital, Ibaraki, Japan
| | - Kazuhiro Miyata
- Department of Physical Therapy, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan
| | - Kenichi Yoshikawa
- Ibaraki Prefectural University of Health Sciences Hospital, Ibaraki, Japan
| | - Masafumi Mizukami
- Department of Physical Therapy, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan
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Shabnam S, Pushpavathi M, Gopi Sankar R, Sridharan KV, Vasanthalakshmi MS. A Comprehensive Application for Grading Severity of Voice Based on Acoustic Voice Quality Index v.02.03. J Voice 2025; 39:287.e1-287.e9. [PMID: 36192290 DOI: 10.1016/j.jvoice.2022.08.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 08/06/2022] [Accepted: 08/08/2022] [Indexed: 10/07/2022]
Abstract
Acoustic Voice Quality Index is a six-variable acoustic model for the multiparametric measurement developed by Maryn et al. Studies have provided evidence regarding the practical usefullness, internal consistency, external validity, diagnostic accuracy, and responsiveness to change of AVQI. Recently, researchers have been exploring the utility of AVQI in classifying the voice severity. The aim of the present study was to determine the diagnostic accuracy of the AVQI v.02.03 in discriminating across the perceptual levels of dysphonia severity in 18-40 years age range in Kannada speaking population; and to develop an application to depict the AVQI based severity of dysphonia. For the study, 163 individuals in normophonic and 134 individuals in dysphonic group were considered in the age range of 18-40 years. All participants were native speakers of Kannada language. The sustained vowel /a/ and reading of standard Kannada passage were considered as stimuli for extracting AVQI analysed using AVQI script version 02.03. The AVQI cut-off values obtained were 2.50 (AROC=0.894; Sensitivity= 84.7%; Specificity= 83.1%), 4.17 (AROC=0.953; Sensitivity= 84.4%; Specificity= 88.5%) and 6.23 (AROC=1.000; Sensitivity= 100%; Specificity= 100%) for normal vs. mild, mild vs. moderate and moderate vs. severe respectively. A user friendly application was developed which provides a simplified output for AVQI cut-off values which can be comprehendible by patients with voice disorder/ non-professionals and health professionals.
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Affiliation(s)
- Srushti Shabnam
- Nitte Institute of Speech and Hearing, Mangalore, Karnataka, India.
| | - M Pushpavathi
- All India Institute of Speech and Hearing, Mysuru, Karnataka, India
| | - R Gopi Sankar
- Department of Clinical Services, All India Institute of Speech and Hearing, Mysuru, Karnataka, India
| | | | - M S Vasanthalakshmi
- Department of Speech Language Pathology, All India Institute of Speech and Hearing, Mysuru, Karnataka, India
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Gaito S, Hwang E, Thwaites D, Ahern V, Smith E, Whitfield GA, Sitch P, France A, Aznar M. Identifying paediatric patients at risk of severe hearing impairment after treatment for malignancies of the H&N/CNS with proton therapy. Radiother Oncol 2025; 202:110597. [PMID: 39490418 DOI: 10.1016/j.radonc.2024.110597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 10/09/2024] [Accepted: 10/23/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND AND PURPOSE A risk calculation model was presented in 2021 by Keilty et al. for determining the likelihood of severe hearing impairment (HI) for paediatric patients treated with photon radiation therapy. This study aimed to validate their risk-prediction model for our cohort of paediatric patients treated with proton therapy (PT) for malignancies of the head and neck (H&N) or central nervous system (CNS). MATERIALS AND METHODS This was a single-institution study which extracted data on all patients aged ≤ 18 years treated with PT between Feb 2010 - Feb 2022 for malignancies of the H&N/CNS. The factors required for input into the Keilty model were extracted: age at PT, time since end of PT, mean cochlea dose, and platinum chemotherapy doses. Validation was performed using the statistical software R v 4.3.1, which analysed event discrimination and model calibration. RESULTS 587 patients met the criteria. Validation of the model demonstrated excellent discriminative ability, with an "optimal" cut-off value of 16% at a specificity and sensitivity of 82%. However, model calibration was less satisfactory, indicating an overestimation of risk of severe hearing loss (HI) by the model as compared to clinically observed events in our cohort, possibly linked to differences in event scoring between the model developers and this study, and short follow-up time in this study. CONCLUSION The published (photon-based) model of Keilty et al. was validated in a PT context, demonstrating a high discriminative ability to determine patients at high risk versus low risk for severe HI. However the overall observed risk was lower than model predictions.
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Affiliation(s)
- Simona Gaito
- Proton Clinical Outcomes Unit, The Christie NHS Foundation Trust, Manchester, United Kingdom; University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Eunji Hwang
- Radiation Oncology Network, Western Sydney Local Health District, NSW, Australia; Institute of Medical Physics, School of Physics, University of Sydney, NSW, Australia.
| | - David Thwaites
- Institute of Medical Physics, School of Physics, University of Sydney, NSW, Australia
| | - Verity Ahern
- Radiation Oncology Network, Western Sydney Local Health District, NSW, Australia; Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, NSW, Australia
| | - Ed Smith
- Proton Clinical Outcomes Unit, The Christie NHS Foundation Trust, Manchester, United Kingdom; University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, Manchester, United Kingdom; The Christie Proton Beam Therapy Centre, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Gillian A Whitfield
- The Christie Proton Beam Therapy Centre, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Peter Sitch
- The Christie Proton Beam Therapy Centre, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Anna France
- Proton Clinical Outcomes Unit, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Marianne Aznar
- University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, Manchester, United Kingdom
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Asaulenko ZP, Krivolapov YA. [Immunohistochemical method of megakaryocytic lineage staining in bone marrow biopsy specimens as an additional pathomorphological differential diagnostic sign of primary myelofibrosis and essential thrombocythemia]. Arkh Patol 2025; 87:22-27. [PMID: 39943725 DOI: 10.17116/patol20258701122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2025]
Abstract
OBJECTIVE To evaluate and compare morphometric and histotopographic characteristics of megakaryocytic lineage in preparations stained with H&E or antibodies to CD42b in diagnostic trepanobioptates of bone marrow of patients with primary myelofibrosis and essential thrombocythemia with JAK2 or CALR mutation. Analyze the dimensions and quantity of CD42b-positive megakaryocytes in 1 mm2 area of section and assess suitability of these parameters as an additional differential pathomorphological criterion. MATERIAL AND METHODS 108 trephine biopsies of the bone marrow from patients with primary myelofibrosis (N=53) and essential thrombocythemia (N=55) with JAK2 or CALR mutation were selected. Digitized bone marrow slides stained with H&E or antibodies to CD42b (clone EP409) were the object of study. In every sample the average values of perimeter and area of megakaryocytes were analyzed, as well as the average number of megakaryocytes in 1 mm2 area of myeloid tissue section. Logistic regression analysis was used to describe the relationship between CD42b-positive megakaryocyte characteristics and disease (primary myelofibrosis or essential thrombocythemia). RESULTS Immunohistochemical examination of bone marrow biopsy specimens using antibodies to CD42b in comparison with H&E staining allows to multiply the number of identifiable megakaryocytes in myeloid tissue by 3.5-4 times (p<0.0001). Statistically significant differences in the mean values of the number of megakaryocytes in 1 mm2 of the section area and megakaryocyte perimeter in patients with primary myelofibrosis and essential thrombocythemia have been demonstrated. ROC analysis (AUC=0.84, 95% CI 0.7782-0.9199) justifies the inclusion of the average perimeter size of CD42b-positive megakaryocytes and their number in 1 mm2 of the section area in the differential diagnostic panel as an additional pathomorphological criterion. CONCLUSION The revealed statistically significant differences in quantitative and geometric characteristics of megakaryocytes allowed to calculate differential threshold values of characteristics of megakaryocytic lineage of myeloid tissue in diagnostic trepanobioptates of bone marrow from patients with primary myelofibrosis and essential thrombocythemia. Counting the number of CD42b-positive megakaryocytes in one field of view at a magnification of 400 times was proposed as an additional pathomorphological differential-diagnostic sign.
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Affiliation(s)
- Z P Asaulenko
- St. Petersburg City Hospital No 40, St. Petersburg, Sestroretsk, Russia
- I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russia
| | - Yu A Krivolapov
- I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russia
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Gotoh T, Kumada T, Ogawa S, Niwa F, Toyoda H, Hirooka M, Koizumi Y, Hiasa Y, Akita T, Tanaka J, Shimizu M. Comparison Between Attenuation Measurement and the Controlled Attenuation Parameter for the Assessment of Hepatic Steatosis Based on MRI Images. Liver Int 2025; 45:e16210. [PMID: 39673700 DOI: 10.1111/liv.16210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 11/21/2024] [Accepted: 11/29/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND AND AIMS This study prospectively compared the diagnostic accuracies of the improved Attenuation Measurement (iATT) algorithm and the Controlled Attenuation Parameter (CAP) and assessed the interchangeability of iATT with magnetic resonance imaging-derived proton density fat fraction (MRI-derived PDFF). METHODS Patients with chronic liver disease were prospectively enrolled and underwent iATT, CAP and MRI-derived PDFF measurements for hepatic steatosis evaluation. According to MRI-derived PDFF values, steatosis grades were categorised as steatosis (S)0 (< 5.2%), S1 (≥ 5.2%, < 11.3%), S2 (≥ 11.3%, < 17.1%) and S3 (≥ 17.1%). Correlation coefficients (CCs) were determined, diagnostic performances were compared by the area under the receiver operating characteristic curve (AUROC) and agreement was evaluated using the calculated percentage error (PE) and expected limit of agreement (LOA). RESULTS A total of 414 patients (median age 64 years, 203 females) were evaluated. The CC between iATT and MRI-derived PDFF was 0.727 (95% confidence interval [CI] 0.678-0.770), which was higher than that between CAP and MRI-derived PDFF at 0.615 (95% CI 0.551-0.672) (p < 0.001). The AUROCs of iATT for ≥ S1, ≥ S2 and ≥ S3 were 0.901 (95% CI 0.870-0.931), 0.878 (95% CI 0.846-0.910) and 0.839 (95% CI 0.794-0.883), respectively. The diagnostic performances of iATT for ≥ S1 and ≥ S2 showed significantly higher AUROCs than those of CAP (p < 0.001, p = 0.036, respectively). The calculated PE and the expected LOA for CAP and iATT were 38.94% and 22.66% and 32.94% and 30.03%, respectively. CONCLUSIONS iATT was superior to CAP and comparable to MRI-derived PDFF in assessing hepatic steatosis. TRIAL REGISTRATION This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000047411).
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Affiliation(s)
- Tatsuya Gotoh
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Sadanobu Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Fumihiko Niwa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabiology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabiology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabiology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan
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