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Maranhão BHF, Junior CTDS, Barillo JL, Souza JBS, Silva PS, Stirbulov R. Total adenosine deaminase cases as an inflammatory biomarker of pleural effusion syndrome. World J Clin Cases 2025; 13:101850. [DOI: 10.12998/wjcc.v13.i19.101850] [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: 09/28/2024] [Revised: 11/04/2024] [Accepted: 03/04/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Although inflammatory diseases commonly affect the pleura and pleural space, their mechanisms of action remain unclear. The presence of several mediators emphasizes the concept of pleural inflammation. Adenosine deaminase (ADA) is an inflammatory mediator detected at increased levels in the pleural fluid.
AIM To determine the role of total pleural ADA (P-ADA) levels in the diagnosis of pleural inflammatory diseases.
METHODS 157 patients with inflammatory pleural effusion (exudates, n = 124, 79%) and non-inflammatory pleural effusion (transudates, n = 33, 21%) were included in this observational retrospective cohort study. The P-ADA assay was tested using a kinetic technique. The performance of the model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The ideal cutoff value for P-ADA in pleural inflammation was determined using the Youden index in the ROC curve.
RESULTS The transudates included congestive heart failure (n = 26), cirrhosis of the liver with ascites (n = 3), chronic renal failure (n = 3), and low total protein levels (n = 1). The exudate cases included tuberculosis (n = 44), adenocarcinoma (n = 37), simple parapneumonic effusions (n = 15), complicated parapneumonic effusions/empyema (n = 8), lymphoma (n = 7), and other diseases (n = 13). The optimal cutoff value of P-ADA was ≥ 9.00 U/L. The diagnostic parameters as sensitivity, specificity, positive and negative predictive values, positive and negative likelihood values, odds ratio, and accuracy were 77.69 (95%CI: 69.22-84.75); 68.75 (95%CI: 49.99-83.88); 90.38 and 44.90 (95%CI: 83.03-95.29; 30.67-59.77); 2.48 and 0.32 (95%CI: 2.21-11.2; 0.27-0.51); 7.65 (95%CI: 0.78-18.34), and 75.82 (95%CI: 68.24-82.37), respectively (χ² = 29.51, P = 0.00001). An AUC value of 0.8107 (95%CI: 0.7174-0.8754; P = 0.0000) was clinically useful. The Hosmer-Lemeshow test showed excellent discrimination.
CONCLUSION P-ADA biomarker has high diagnostic performance for pleural inflammatory exudates.
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Affiliation(s)
- Bernardo Henrique Ferraz Maranhão
- Department of Specialized Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270004, State of Rio de Janeiro, Brazil
| | | | - Jorge Luiz Barillo
- Department of Thoracic Surgery, General Hospital Santa Teresa, Petropolis 25680-003, Rio de Janeiro, Brazil
| | | | - Patricia Siqueira Silva
- Professor Mazzini Bueno Tuberculosis Research and Assistance Center, Federal Fluminense University, Niteroi 24020-080, Rio de Janeiro, Brazil
| | - Roberto Stirbulov
- Department of Clinics, Rua Baronesa de Itu, São Paulo 1231001, São Paulo, Brazil
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Cigarán-Mendez M, Tejera-Alonso Á, Gómez-Calero C, Fernández-de-las-Peñas C, López-Redondo M, Valera-Calero JA, Fernández-Palacios FG, Pacho-Hernández JC. Can Clinical, Psychological, and Cognitive Patient-Reported Outcome Measures (PROMs) Help to Discriminate Women with Fibromyalgia from Those with Other Localized/Regional Pain Conditions? A Diagnostic Accuracy Study. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:359. [PMID: 40005475 PMCID: PMC11857717 DOI: 10.3390/medicina61020359] [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: 01/08/2025] [Revised: 02/16/2025] [Accepted: 02/18/2025] [Indexed: 02/27/2025]
Abstract
Background and Objectives: The heterogeneous clinical manifestations of fibromyalgia syndrome have led to the revision of diagnostic criteria in the last decade. The aim of this study was to determine the capability of clinical, psychological, and cognitive patient-related outcome measures (PROMs) to differentiate women with fibromyalgia syndrome (FMS) from women with localized or regional pain conditions. Materials and Methods: A diagnostic accuracy study was conducted. Clinical (pain intensity-NPRS; related disability-FIQ), psychological (anxiety/depressive levels-HADS-A/HADS-D), and cognitive (sleep quality-PSQI; pain hypervigilance-PVAQ-9) PROMs were collected in 129 women with FMS and 65 women with localized/regional chronic pain conditions. The area under the receiver operating characteristic (ROC) curve, cut-off point, sensitivity/specificity values, and positive and negative likelihood (LR) ratios of each variable were calculated. Results: Women with FMS showed higher levels of pain, related disability, and anxiety/depressive levels, worse sleep quality, and higher levels of hypervigilance (all, p < 0.001) than women without FMS. All PROMs showed excellent discriminatory power and good sensitivity (pain intensity: ROC 0.987, sensitivity 91.5%; related disability: ROC 0.980, sensitivity 93.8%; HADS-A: ROC 0.901, sensitivity 81.4%; HADS-D: ROC 0.906, sensitivity 85.3%; PSQI: ROC 0.909, sensitivity 79.1%; PVAQ-9: ROC 0.798, sensitivity 80.6%). Specificity was extremely small for all variables (<18%) except for pain hypervigilance (specificity: 34%). Conclusions: Women with FMS exhibited worse clinical, psychological, and cognitive variables than women with localized/regional chronic pain. Although all PROMs had good discriminatory power, related disability and pain hypervigilance were those showing the best models. These PROMs could be combined with the American College of Rheumatology (ACR) diagnostic criteria to better discriminate between women with and without FMS. Studies investigating the relevance of combining these PROMs with the ACR diagnostic criteria in clinical settings are needed.
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Affiliation(s)
- Margarita Cigarán-Mendez
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.); (J.C.P.-H.)
| | - Ángela Tejera-Alonso
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.); (J.C.P.-H.)
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Cristina Gómez-Calero
- Department Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain;
| | - César Fernández-de-las-Peñas
- Department Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain;
| | - Mónica López-Redondo
- Faculty of Health Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain;
| | - Juan A. Valera-Calero
- Department of Radiology, Rehabilitation and Physiotherapy, Faculty of Nursery, Physiotherapy and Podiatry, Complutense University of Madrid, 28040 Madrid, Spain;
- Grupo InPhysio, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - Francisco G. Fernández-Palacios
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.); (J.C.P.-H.)
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Juan C. Pacho-Hernández
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.); (J.C.P.-H.)
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3
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Cigarán-Mendez M, Pacho-Hernández JC, Fernández-Palacios FG, Tejera-Alonso Á, Valera-Calero JA, Gómez-Calero C, Ordás-Bandera C, Fernández-de-las-Peñas C. Can Clinical, Psychophysical or Psychological Variables Help in Discriminating Women with Migraines from a Tertiary Center? A Diagnostic Accuracy Study. Diagnostics (Basel) 2024; 14:2805. [PMID: 39767166 PMCID: PMC11674706 DOI: 10.3390/diagnostics14242805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/05/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Migraine diagnosis is mainly clinically based on symptomatology. The objectives of this study were (1) to determine the ability of pain thresholds to differentiate between women with and without migraines and (2) to determine the ability of clinical, psychological and psychophysical variables to differentiate between women with episodic and chronic migraines. A diagnostic accuracy study was conducted. Methods: Pressure-pain thresholds (PPTs) at one trigeminal (temporalis muscle) and one extra-trigeminal (cervical spine) and two distant-pain free (second metacarpal and tibialis anterior muscle) areas, as well as dynamic pain thresholds (DPTs), were bilaterally assessed in 100 women with migraines, recruited from tertiary hospitals (50% episodic, 50% chronic), and 50 comparable women without headaches. Migraine pain features (headache diary), migraine-associated burden (HDI), anxiety and depressive levels (HADS) and state (STAI-S)-trait (STAI-T) anxiety were also evaluated. The area under the receiver operating characteristic (ROC) curve, with optimal cut-off points, as well as the sensitivity, specificity and positive/negative likelihood ratios (LR) for each variable, were calculated. The women with migraines showed lower PPTs and DPTs than those without migraines. Results: The women with chronic migraines showed lower PPTs in the temporalis muscle than the women with episodic migraines. No clinical, psychological or psychophysical variables exhibited acceptable ROC values (≥0.7) for differentiating between women with and without migraines or between women with episodic and chronic migraines. Conclusions: Although the women with migraines had widespread pressure-pain hyperalgesia, neither the clinical, psychological nor psychophysical (pain threshold) variable exhibited the proper diagnostic accuracy to distinguish between women with and without migraines or between women with episodic and chronic migraines. New studies should clarify the clinical relevance of the findings of the current study.
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Affiliation(s)
- Margarita Cigarán-Mendez
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (J.C.P.-H.); (F.G.F.-P.)
| | - Juan C. Pacho-Hernández
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (J.C.P.-H.); (F.G.F.-P.)
| | - Francisco G. Fernández-Palacios
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (J.C.P.-H.); (F.G.F.-P.)
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Ángela Tejera-Alonso
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (J.C.P.-H.); (F.G.F.-P.)
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Juan A. Valera-Calero
- Department of Radiology, Rehabilitation and Physiotherapy, Faculty of Nursery, Physiotherapy and Podiatry, Complutense University of Madrid, 28040 Madrid, Spain;
- Grupo InPhysio, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - Cristina Gómez-Calero
- Department Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain;
| | | | - César Fernández-de-las-Peñas
- Department Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain;
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Jukema RA, Dahdal J, Kooijman EM, Wahedi E, de Winter RW, Guglielmo M, Cramer MJ, van der Harst P, Remmelzwaal S, Raijmakers P, Knaapen P, Danad I. Diagnostic accuracy of non-invasive cardiac imaging modalities in patients with a history of coronary artery disease: a meta-analysis. Heart 2024; 111:4-10. [PMID: 39179368 PMCID: PMC11671941 DOI: 10.1136/heartjnl-2024-324248] [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: 04/04/2024] [Accepted: 08/03/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND The diagnostic performance of non-invasive imaging techniques for detecting obstructive coronary artery disease (CAD) in patients with a history of myocardial infarction or percutaneous coronary intervention has not been comprehensively evaluated. This meta-analysis assesses the diagnostic value of coronary CT angiography (CCTA), CCTA combined with CT perfusion (CCTA+CTP), cardiac MRI (CMR) and single-photon emission CT (SPECT) compared with invasive reference standards. METHODS We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from 2005 to September 2022 for prospective, blinded studies including populations with ≥50% prior CAD. RESULTS We identified 18 studies encompassing 3265 patients, with obstructive CAD present in 64%. The per-patient sensitivity of CCTA (0.95; 95% CI 0.92 to 0.98), CCTA+CTP (0.93; 95% CI 0.84 to 0.98) and CMR (0.91; 95% CI 0.86 to 0.94) was high, while SPECT showed lower sensitivity (0.63; 95% CI 0.52 to 0.73). SPECT had higher specificity compared with CCTA (0.66; 95% CI 0.56 to 0.76 vs 0.37; 95% CI 0.29 to 0.46), but was comparable to CCTA+CTP (0.59; 95% CI 0.49 to 0.69) and CMR (0.69; 95% CI 0.53 to 0.81). The area under the curve for SPECT was the lowest (0.70; 95% CI 0.58 to 0.87), while CCTA (0.91; 95% CI 0.86 to 0.98), CCTA+CTP (0.89; 95% CI 0.73 to 1.00) and CMR (0.91; 95% CI 0.80 to 1.00) showed similar high values. CONCLUSIONS In patients with prior CAD, CCTA, CCTA+CTP and CMR demonstrated high diagnostic performance, whereas SPECT had lower sensitivity. These findings can guide the selection of non-invasive imaging techniques in this high-risk population. PROSPERO REGISTRATION NUMBER CRD42022322348.
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Affiliation(s)
- Ruurt A Jukema
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jorge Dahdal
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Medicine, Hospital del Salvador, Santiago, Chile
| | - Eline M Kooijman
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ellaha Wahedi
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ruben W de Winter
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Marco Guglielmo
- Division of Heart and Lungs, Department of Cardiology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Maarten Jan Cramer
- Division of Heart and Lungs, Department of Cardiology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Pim van der Harst
- Division of Heart and Lungs, Department of Cardiology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Sharon Remmelzwaal
- Epidemiology and Biostatistics, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Pieter Raijmakers
- Department of Radiology, Nuclear Medicine & PET Research, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Paul Knaapen
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ibrahim Danad
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Division of Heart and Lungs, Department of Cardiology, Utrecht University Medical Center, Utrecht, The Netherlands
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Cigarán-Mendez M, Pacho-Hernández JC, Tejera-Alonso Á, Gómez-Calero C, Fernández-de-las-Peñas C, Valera-Calero JA, Fernández-Palacios FG. Diagnostic Accuracy of Neurocognitive and Executive Functions to Discriminate Women With and Without Fibromyalgia Syndrome: A Secondary Analysis. J Clin Med 2024; 13:6195. [PMID: 39458147 PMCID: PMC11508891 DOI: 10.3390/jcm13206195] [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: 09/18/2024] [Revised: 10/07/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Objective: The aim of the current study was to determine the capability of neurocognitive variables and executive functions to differentiate women with and without fibromyalgia syndrome (FMS). Methods: A secondary diagnostic accuracy analysis was conducted. A battery of neurocognitive and executive function tests (the D2 Attention test, the Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit test for mental inhibition, the Symbol Search for processing speed, and the Zoo Test for planning/decision-making) were collected in 129 women with FMS and 111 without FMS. The area under the receiver operating characteristic (ROC) curve, optimal cut-off point, sensitivity, specificity, and positive and negative likelihood ratios (LR) for each variable were calculated. Results: Between-group differences were identified in ROCF_Copy (p = 0.043), ROCF_Recall (p = 0.004), d2_TR (p = 0.019), d2_TA (p = 0.007), d2_TOT (p = 0.005), d2_CON (p = 0.004), d2_C (p = 0.042), Symbol Search (p = 0.008), Decoding _FDT (p = 0.001), Retrieving_FDT (p = 0.001), and Inhibiting_FDT (p = 0.024). The result showed that FDT-based outcomes (Retrieving_FDT: ROC 0.739, sensitivity 85.3%, specificity 48.6%; Decoding_FDT: ROC 0.724, sensitivity 50.4%, specificity 16.2%; Inhibiting_FDT: ROC 0.708, sensitivity 56.6%, specificity 22.5%) were the variables able to differentiate between women with and without FMS. Conclusions: Although women with FMS exhibited deficits in attention, long-term visual memory, processing speed, and mental inhibition when compared with women without FMS, only mental inhibition scores showed moderate diagnostic accuracy to discriminate between women with and without FMS. Future studies investigating these results in clinical settings are needed to identify the clinical relevance of these findings.
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Affiliation(s)
- Margarita Cigarán-Mendez
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.)
| | - Juan C. Pacho-Hernández
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.)
| | - Ángela Tejera-Alonso
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.)
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Cristina Gómez-Calero
- Department Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (C.G.-C.); (C.F.-d.-l.-P.)
| | - César Fernández-de-las-Peñas
- Department Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (C.G.-C.); (C.F.-d.-l.-P.)
| | - Juan A. Valera-Calero
- Department of Radiology, Rehabilitation and Physiotherapy, Faculty of Nursery, Physiotherapy and Podiatry, Complutense University of Madrid, 28040 Madrid, Spain;
- Grupo InPhysio, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - Francisco G. Fernández-Palacios
- Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain; (M.C.-M.); (Á.T.-A.); (F.G.F.-P.)
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain
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Hosseinpour H, Anand T, Bhogadi SK, Nelson A, Hejazi O, Castanon L, Ghaedi A, Khurshid MH, Magnotti LJ, Joseph B. The implications of poor nutritional status on outcomes of geriatric trauma patients. Surgery 2024; 176:1281-1288. [PMID: 39060117 DOI: 10.1016/j.surg.2024.06.047] [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: 03/29/2024] [Revised: 05/26/2024] [Accepted: 06/13/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Malnutrition is shown to be associated with worse outcomes among surgical patients, yet its postdischarge outcomes in trauma patients are not clear. This study aimed to evaluate both index admission and postdischarge outcomes of geriatric trauma patients who are at risk of poor nutritional status. METHODS This is a secondary analysis of the prospective observational American Association of Surgery for Trauma Frailty Multi-institutional Trial. Geriatric (≥65 years) patients presenting to 1 of the 17 Level I/II/III trauma centers (2019-2021) were included and stratified using the simplified Geriatric Nutritional Risk Index (albumin [g/dL] + body mass index [kg/m2]/10) into severe (simplified Geriatric Nutritional Risk Index <5), moderate (5.5> simplified Geriatric Nutritional Risk Index ≥5), mild level of nutritional risk (6> simplified Geriatric Nutritional Risk Index ≥5.5), and good nutritional status (simplified Geriatric Nutritional Risk Index ≥6) and compared. RESULTS Of the 1,321 patients enrolled, 22% were at risk of poor nutritional status (mild: 13%, moderate: 7%, severe: 3%). The mean age was 77 ± 8 years, and the median [interquartile range] Injury Severity Score was 9 [5-13]. Patients at risk of poor nutritional status had greater rates of sepsis, pneumonia, discharge to the skilled nursing facility and rehabilitation center, index-admission mortality, and 3-month mortality (P < .05). On multivariable analyses, being at risk of severe level of nutritional risk was independently associated with sepsis (adjusted odds ratio 6.21, 95% confidence interval 1.68-22.90, P = .006), pneumonia (adjusted odds ratio 4.40, 95% confidence interval 1.21-16.1, P = .025), index-admission mortality (adjusted odds ratio 3.16, 95% confidence interval 1.03-9.68, P = .044), and 3-month mortality (adjusted odds ratio 8.89, 95% confidence interval 2.01-39.43, P = .004) compared with good nutrition state. CONCLUSION Nearly one quarter of geriatric trauma patients were at risk of poor nutritional status, which was identified as an independent predictor of worse index admission and 3-month postdischarge outcomes. These findings underscore the need for nutritional screening at admission.
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Affiliation(s)
- Hamidreza Hosseinpour
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Tanya Anand
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Sai Krishna Bhogadi
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Adam Nelson
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Omar Hejazi
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Lourdes Castanon
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Arshin Ghaedi
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Muhammad Haris Khurshid
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Louis J Magnotti
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ
| | - Bellal Joseph
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ.
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Hosseinpour H, Stewart C, Hejazi O, Okosun SE, Khurshid MH, Nelson A, Bhogadi SK, Ditillo M, Magnotti LJ, Joseph B. FINDING THE SWEET SPOT: THE ASSOCIATION BETWEEN WHOLE BLOOD TO RED BLOOD CELLS RATIO AND OUTCOMES OF HEMORRHAGING CIVILIAN TRAUMA PATIENTS. Shock 2024; 62:344-350. [PMID: 38888586 DOI: 10.1097/shk.0000000000002405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2024]
Abstract
ABSTRACT Purpose: To evaluate the dose-dependent effect of whole blood (WB) on the outcomes of civilian trauma patients with hemorrhagic shock. Methods: We performed a 2-year (2020-2021) retrospective analysis of the ACS-TQIP dataset. Adult (≥18) trauma patients with a shock index (SI) >1 who received at least 5 units of PRBC and one unit of WB within the first 4 h of admission were included. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications and hospital and intensive care unit length of stay. Results: A total of 830 trauma patients with a mean (SD) age of 38 (16) were identified. The median [IQR] 4-h WB and PRBC requirements were 2 [2-4] U and 10 [7-15] U, respectively, with a median WB:RBC ratio of 0.2 [0.1-0.3]. Every 0.1 increase in WB:RBC ratio was associated with decreased odds of 24-h mortality (aOR: 0.916, P = 0.035) and in-hospital mortality (aOR: 0.878, P < 0.001). Youden's index identified 0.25 (1 U of WB for every 4 U of PRBC) as the optimal WB:PRBC ratio to reduce 24-h mortality. High ratio (≥0.25) group had lower adjusted odds of 24-h mortality (aOR: 0.678, P = 0.021) and in-hospital mortality (aOR: 0.618, P < 0.001) compared to the low ratio group. Conclusions: A higher WB:PRBC ratio was associated with improved early and late mortality in trauma patients with hemorrhagic shock. Given the availability of WB in trauma centers across the United States, at least one unit of WB for every 4 units of packed red blood cells may be administered to improve the survival of hemorrhaging civilian trauma patients.
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Affiliation(s)
- Hamidreza Hosseinpour
- Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, Arizona
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Garbern SC, Islam MT, Islam K, Ahmed SM, Brintz BJ, Khan AI, Taniuchi M, Platts-Mills JA, Qadri F, Leung DT. Derivation and External Validation of a Clinical Prediction Model for Viral Diarrhea Etiology in Bangladesh. Open Forum Infect Dis 2023; 10:ofad295. [PMID: 37404954 PMCID: PMC10316693 DOI: 10.1093/ofid/ofad295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 05/26/2023] [Indexed: 07/06/2023] Open
Abstract
Background Antibiotics are commonly overused for diarrheal illness in many low- and middle-income countries, partly due to a lack of diagnostics to identify viral cases, in which antibiotics are not beneficial. This study aimed to develop clinical prediction models to predict risk of viral-only diarrhea across all ages, using routinely collected demographic and clinical variables. Methods We used a derivation dataset from 10 hospitals across Bangladesh and a separate validation dataset from the icddr,b Dhaka Hospital. The primary outcome was viral-only etiology determined by stool quantitative polymerase chain reaction. Multivariable logistic regression models were fit and externally validated; discrimination was quantified using area under the receiver operating characteristic curve (AUC) and calibration assessed using calibration plots. Results Viral-only diarrhea was common in all age groups (<1 year, 41.4%; 18-55 years, 17.7%). A forward stepwise model had AUC of 0.82 (95% confidence interval [CI], .80-.84) while a simplified model with age, abdominal pain, and bloody stool had AUC of 0.81 (95% CI, .78-.82). In external validation, the models performed adequately although less robustly (AUC, 0.72 [95% CI, .70-.74]). Conclusions Prediction models consisting of 3 routinely collected variables can accurately predict viral-only diarrhea in patients of all ages in Bangladesh and may help support efforts to reduce inappropriate antibiotic use.
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Affiliation(s)
- Stephanie Chow Garbern
- Department of Emergency Medicine, Alpert Medical School, Brown University, Providence, Rhode Island, USA
| | | | - Kamrul Islam
- Infectious Diseases Division, icddr,b, Dhaka, Bangladesh
| | - Sharia M Ahmed
- Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Ben J Brintz
- Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | | | - Mami Taniuchi
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - James A Platts-Mills
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - Firdausi Qadri
- Infectious Diseases Division, icddr,b, Dhaka, Bangladesh
| | - Daniel T Leung
- Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, USA
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Pre-procedure oral administration of pronase improves efficacy of lugol chromoendoscopy in esophageal squamous cell carcinoma screening: a prospective, double-blinded, randomized, controlled trial. Surg Endosc 2023:10.1007/s00464-023-09902-1. [PMID: 36781469 DOI: 10.1007/s00464-023-09902-1] [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: 09/23/2022] [Accepted: 01/18/2023] [Indexed: 02/15/2023]
Abstract
BACKGROUND AND AIMS Chromoendoscopy with Lugol's staining is used to screen for early esophageal squamous cell carcinoma (ESCC). Its efficacy is greatly limited by unstandardized defoaming preparation. This study aimed to confirm whether pre-procedure oral administration of pronase could improve the diagnostic performance of Lugol chromoendoscopy in high-risk patients being screened for early ESCC. METHODS A total of 955 patients at-risk were prospectively recruited for screening for ESCC. Patients were randomly assigned (1:1) to groups with or without (control group) pronase administration. Endoscopic diagnosis of early ESCC was based on the presence of pink-color sign in Lugol's unstained area, and a biopsy was routinely conducted if the Lugol's unstained lesion was larger than 0.5 cm. The early cancer detection rate was used as the primary endpoint. RESULTS Pre-procedure oral administration of pronase improved mucosal visibility during Lugol chromoendoscopy (P = 0.008). There were no differences in the number of Lugol's unstained lesions between the 2 groups (23.27% [111/477] vs. 25.11% [120/478], P = 0.508). Meaningfully, the detection rate of ESCC (confirmed by histopathology) was significantly higher in the pronase group than in the control group (27.03% [30/111] vs. 17.50% [21/120], P = 0.041), as well as the detection rate of lesions with pink-color sign during chromoendoscopy (35.14% [39/111] vs. 13.33% [16/120], P < 0.001). The diagnostic performance of Lugol chromoendoscopy had improved with the use of pronase (area under the curve = 0.85 vs. 0.69, P = 0.019), accompanied by an increased sensitivity (86.67% vs. 47.62%, P = 0.004). There was no difference in the adverse events between the 2 groups (P = 0.793). CONCLUSIONS Pre-procedure oral administration of pronase significantly increased the detection rate of early ESCC and optimized the diagnostic performance of Lugol chromoendoscopy, which should be recommended during routine endoscopic screening for early ESCC in high-risk patients. TRIAL REGISTRATION Pronase improves efficacy of Lugol chromoendoscopy screening on esophageal cancerous lesions (NCT02030769).
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10
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Machine learning to improve frequent emergency department use prediction: a retrospective cohort study. Sci Rep 2023; 13:1981. [PMID: 36737625 PMCID: PMC9898278 DOI: 10.1038/s41598-023-27568-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 01/04/2023] [Indexed: 02/05/2023] Open
Abstract
Frequent emergency department use is associated with many adverse events, such as increased risk for hospitalization and mortality. Frequent users have complex needs and associated factors are commonly evaluated using logistic regression. However, other machine learning models, especially those exploiting the potential of large databases, have been less explored. This study aims at comparing the performance of logistic regression to four machine learning models for predicting frequent emergency department use in an adult population with chronic diseases, in the province of Quebec (Canada). This is a retrospective population-based study using medical and administrative databases from the Régie de l'assurance maladie du Québec. Two definitions were used for frequent emergency department use (outcome to predict): having at least three and five visits during a year period. Independent variables included sociodemographic characteristics, healthcare service use, and chronic diseases. We compared the performance of logistic regression with gradient boosting machine, naïve Bayes, neural networks, and random forests (binary and continuous outcome) using Area under the ROC curve, sensibility, specificity, positive predictive value, and negative predictive value. Out of 451,775 ED users, 43,151 (9.5%) and 13,676 (3.0%) were frequent users with at least three and five visits per year, respectively. Random forests with a binary outcome had the lowest performances (ROC curve: 53.8 [95% confidence interval 53.5-54.0] and 51.4 [95% confidence interval 51.1-51.8] for frequent users 3 and 5, respectively) while the other models had superior and overall similar performance. The most important variable in prediction was the number of emergency department visits in the previous year. No model outperformed the others. Innovations in algorithms may slightly refine current predictions, but access to other variables may be more helpful in the case of frequent emergency department use prediction.
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Luo H, Liu D, Liu W, Jin J, Bi X, Zhang P, Gu J, Zheng M, Xiao M, Liu X, Zhou J, Wang QF. Clinical and genetic characterization of Epstein-Barr virus-associated T/NK-cell lymphoproliferative diseases. J Allergy Clin Immunol 2022; 151:1096-1109. [PMID: 36423698 DOI: 10.1016/j.jaci.2022.11.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 11/10/2022] [Accepted: 11/16/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Epstein-Barr virus (EBV)-associated T-/natural killer (T/NK)-cell lymphoproliferative diseases clinically take on various forms, ranging from an indolent course to an aggressive condition. OBJECTIVE Clinically, failure to establish precise diagnosis and provide proper treatment makes it difficult to help patients. We sought to better understand the underlying pathogenesis and to identify genetic prognostic factors to achieve better treatment efficacy. METHODS In this study, 119 cases of EBV-associated lymphoproliferative diseases, including EBV-associated hemophagocytic lymphohistiocytosis (n = 46) and chronic active EBV disease of T/NK cell type (n = 73), were retrospectively examined. RESULTS Adults aged >20 years at onset accounted for 71.4% of our cohort. About 54.6% patients with unfavorable overall survival developed hemophagocytic lymphohistiocytosis and had higher plasma EBV load. Allogenic hematopoietic stem-cell transplantation was the sole independent favorable factor. We systematically screened germline and somatic aberrations by whole-exome and targeted sequencing. Among 372 antiviral immunity genes, germline variants of 8 genes were significantly enriched. From a panel of 24 driver genes, somatic mutations were frequently identified in dominant EBV-infected T/NK cells. Patients carrying any germline/somatic aberrations in epigenetic modifiers and RIG-I-like receptor (RLR) pathway had worse overall survival than those without 2 type aberrations. Importantly, patients with IFIH1 and/or DDX3X aberrations in the RLR pathway had higher plasma and NK-cell EBV load. Knockdown of DDX3X in NKYS cells downregulated RLR signaling activities and elevated the expression of EBV-encoded oncogenes such as LMP1 and EBNA1. CONCLUSION Genetic defects were prevalent in adult EBV-associated hemophagocytic lymphohistiocytosis patients and patients with chronic active EBV disease of T/NK cell type; these defects were associated with unfavorable prognosis. These findings can help clinicians work out more precise staging of the condition and provide new insights into these EBV-associated diseases.
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Affiliation(s)
- Hui Luo
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Dan Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
| | - Wenbing Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
| | - Jin Jin
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Xiaoman Bi
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
| | - Peiling Zhang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Jia Gu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Miao Zheng
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Min Xiao
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Xin Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
| | - Jianfeng Zhou
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Qian-Fei Wang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
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Tsang C, Leung J, Kwok T. Self-perceived balance confidence is independently associated with any subsequent falls and injurious falls among community-dwelling older fallers: A prospective cohort study. Arch Gerontol Geriatr 2022; 103:104776. [PMID: 35870272 DOI: 10.1016/j.archger.2022.104776] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/26/2022] [Accepted: 07/07/2022] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Balance confidence contributes to activity restriction, decline in physical function, and falls, potentially. This study aimed at examining whether balance confidence is a significant fall predictor independent of physical function measures in community-dwelling older adults. METHODS This was an observational cohort study. Self-perceived balance confidence was measured by the Activities-specific Balance Confidence scale (ABC) and the short form of it, ABC-6. Other potential predictors included gait speed, Five Times Sit-to-Stand Test, Physiological Profile Assessment (PPA), age, sex, cognition, depression, arthritis, body mass index, recurrent fall history, number of comorbidities, number of prescribed medications, and the use of walking aids. Fall occurrence and subsequent injuries were followed up trimonthly for 12 months. The association of the potential predictors with falls was examined with multivariable logistic regression analyses. Sensitivity analysis for their association with injurious falls in a year was performed. RESULTS 461 community-dwelling older adults with a fall history in the past year completed the 12-month follow-up (mean age 70.6±7.1 years, range 60-92 years; 81% females). Participants with high balance confidence (ABC score ≥76 and ABC-6 score ≥64) were less likely to fall in the subsequent year, independently of the physical function measures and other covariates (adjusted OR 0.51-0.57, 95%CI 0.30-0.97, p<0.05). CONCLUSION Balance confidence is a significant fall predictor independent of physical function measures and other covariates in community-dwelling older adults with a history of falls. Future studies might investigate the causal effects of balance confidence on the risk of falling with randomized controlled trials.
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Affiliation(s)
- Charlotte Tsang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; The Chinese University of Hong Kong Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong
| | - Jason Leung
- The Chinese University of Hong Kong Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong
| | - Timothy Kwok
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; The Chinese University of Hong Kong Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong.
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Castro-Pearson S, Le CT, Luo X. Two-sample survival probability curves: A graphical approach for the analysis of time to event data in clinical trials. Contemp Clin Trials 2022; 115:106707. [PMID: 35176502 PMCID: PMC9018539 DOI: 10.1016/j.cct.2022.106707] [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: 07/28/2021] [Revised: 12/29/2021] [Accepted: 02/09/2022] [Indexed: 11/03/2022]
Abstract
With the aim to improve the communication of trial results, we introduce a novel graphical approach that complements the analysis of time to event outcomes in two-arm randomized trials. We define the so-called two-sample survival probability curve and propose a nonparametric estimator of the curve based on a random walk using Kaplan-Meier survival estimates for the two arms. We then use the estimated curve to visualize treatment effect as well as potential effect modification of factors of interest. We also propose to estimate two-sample survival probability curves within the framework of the Cox model to graphically assess model fit. The proposed two-sample survival probability plot puts trials in a standardized [0,1] × [0,1] space, allowing for a simple visualization of the main effect, effect modification, and the adequacy of a model fit.
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Affiliation(s)
- Sandra Castro-Pearson
- Division of Biostatistics, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
| | - Chap T Le
- Division of Biostatistics, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
| | - Xianghua Luo
- Division of Biostatistics, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
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Felline A, Seeber M, Fanelli F. PSNtools for standalone and web-based structure network analyses of conformational ensembles. Comput Struct Biotechnol J 2022; 20:640-649. [PMID: 35140884 PMCID: PMC8801349 DOI: 10.1016/j.csbj.2021.12.044] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 12/22/2021] [Accepted: 12/30/2021] [Indexed: 12/03/2022] Open
Abstract
Structure graphs, in which interacting amino acids/nucleotides correspond to linked nodes, represent cutting-edge tools to investigate macromolecular function. The graph-based approach defined as Protein Structure Network (PSN) was initially implemented in the Wordom software and subsequently in the webPSN server. PSNs are computed either on a molecular dynamics (MD) trajectory (PSN-MD) or on a single structure. In the latter case, information on atomic fluctuations is inferred from the Elastic Network Model-Normal Mode Analysis (ENM-NMA) (PSN-ENM). While Wordom performs both PSN-ENM and PSN-MD analyses but without output post-processing, the webPSN server performs only single-structure PSN-EMN but assisting the user in input setup and output analysis. Here we release for the first time the standalone software PSNtools, which allows calculation and post-processing of PSN analyses carried out either on single structures or on conformational ensembles. Relevant unique and novel features of PSNtools are either comparisons of two networks or computations of consensus networks on sets of homologous/analogous macromolecular structures or conformational ensembles. Network comparisons and consensus serve to infer differences in functionally different states of the same system or network-based signatures in groups of bio-macromolecules sharing either the same functionality or the same fold. In addition to the new software, here we release also an updated version of the webPSN server, which allows performing an interactive graphical analysis of PSN-MD, following the upload of the PSNtools output. PSNtools, the auxiliary binary version of Wordom software, and the WebPSN server are freely available at http://webpsn.hpc.unimo.it/wpsn3.php.
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15
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Luan D, Dadhania DM, Ding R, Muthukumar T, Lubetzky M, Lee JR, Sharma VK, August P, Mueller FB, Schwartz JE, Suthanthiran M. FOXP3 mRNA Profile Prognostic of Acute T Cell-mediated Rejection and Human Kidney Allograft Survival. Transplantation 2021; 105:1825-1839. [PMID: 33031221 PMCID: PMC8024419 DOI: 10.1097/tp.0000000000003478] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND T cell-mediated rejection (TCMR) is the most frequent type of acute rejection and is associated with kidney allograft failure. Almost 40% of TCMR episodes are nonresponsive to therapy, and molecular mechanisms for the nonresponsiveness are unknown. Our single-center study identified that urinary cell FOXP3 mRNA abundance predicts TCMR reversibility and allograft survival. METHODS We developed PCR assays and measured absolute copy numbers of transcripts for FOXP3, CD25, CD3E, perforin, and 18S rRNA in 3559 urines from 480 kidney allograft recipients prospectively enrolled in the multicenter Clinical Trials in Organ Transplantation-04. In this replication study, we investigated the association between mRNA profile and TCMR diagnosis, TCMR reversibility, and allograft survival. RESULTS 18S rRNA normalized levels of mRNA for FOXP3 (P = 0.01, Kruskal-Wallis test), CD25 (P = 0.01), CD3E (P < 0.0001), and perforin (P < 0.0001) were diagnostic of TCMR, but only FOXP3 mRNA level predicted TCMR reversibility (ROC AUC = 0.764; 95% confidence interval, 0.611-0.917; P = 0.008). Multivariable logistic regression analyses showed that urinary cell FOXP3 mRNA level predicted reversal, independent of clinical variables. A composite model of clinical variables and FOXP3 mRNA (AUC = 0.889; 95% CI, 0.781-0.997; P < 0.001) outperformed FOXP3 mRNA or clinical variables in predicting TCMR reversibility (P = 0.01, likelihood ratio test). Multivariable Cox proportional hazards regression analyses showed that FOXP3 mRNA level predicts kidney allograft survival (P = 0.047) but not after controlling for TCMR reversal (P = 0.477). CONCLUSIONS Urinary cell level of FOXP3 mRNA is diagnostic of TCMR, predicts TCMR reversibility, and is prognostic of kidney allograft survival via a mechanism involving TCMR reversal.
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Affiliation(s)
- Danny Luan
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Darshana M. Dadhania
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Ruchuang Ding
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Thangamani Muthukumar
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Michelle Lubetzky
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - John R. Lee
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Vijay K. Sharma
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Phyllis August
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Franco B. Mueller
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
| | - Joseph E. Schwartz
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
| | - Manikkam Suthanthiran
- Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
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Gorga SM, Carlton EF, Kohne JG, Barbaro RP, Basu RK. Consensus acute kidney injury criteria integration identifies children at risk for long-term kidney dysfunction after multiple organ dysfunction syndrome. Pediatr Nephrol 2021; 36:1637-1646. [PMID: 33427986 PMCID: PMC8087651 DOI: 10.1007/s00467-020-04865-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/12/2020] [Accepted: 11/17/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND The consensus definition of acute kidney injury (AKI) has evolved since developing the original multiple organ dysfunction syndrome (MODS) definitions. Whether or not risk for adverse short- and long-term outcomes can be identified using the refined AKI criteria in the setting of MODS has not been studied. We hypothesize that incorporation of Kidney Disease: Improving Global Outcome (KDIGO) AKI criteria into existing MODS definitions will have a higher association with major adverse kidney events at 30 days (MAKE30) and will increase the number of patients with MODS. METHODS Post hoc analysis of 410 children admitted to a tertiary care pediatric intensive care unit (PICU) was conducted. MODS was defined using two existing criteria (Goldstein and Proulx) during the first 7 days following ICU admission and then modified by replacement of the kidney injury criteria using the KDIGO AKI definitions (G' and P'). RESULTS MAKE30 occurred in 65 of 410 (16%) children. After substituting KDIGO kidney injury criteria, identification of MAKE30 increased from 46 children (71%) to 53 (82%) and 29 children (45%) to 43 (66%) for the Goldstein and Proulx criteria, respectively. Additionally, identification of MODS increased from 194 (47%) by Goldstein to 224 (55%) by G' and 95 children (23%) by Proulx to 132 (32%) by P'. CONCLUSIONS Substituting KDIGO AKI criteria into existing MODS criteria increases the sensitivity for major adverse kidney events as well as the identification of MODS, improving the detection of children at risk for long-term adverse renal outcomes.
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Affiliation(s)
- Stephen M Gorga
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA.
| | - Erin F Carlton
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, USA
| | - Joseph G Kohne
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, USA
| | - Ryan P Barbaro
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, USA
| | - Rajit K Basu
- Children's Healthcare of Atlanta/Emory University, Atlanta, GA, USA
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Hakroush S, Tampe D, Korsten P, Ströbel P, Zeisberg M, Tampe B. Histopathological Findings Predict Renal Recovery in Severe ANCA-Associated Vasculitis Requiring Intensive Care Treatment. Front Med (Lausanne) 2021; 7:622028. [PMID: 33634143 PMCID: PMC7900153 DOI: 10.3389/fmed.2020.622028] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/23/2020] [Indexed: 11/13/2022] Open
Abstract
Renal involvement is a common and severe complication of AAV as it can cause ESRD. Histopathological subgrouping and ARRS are helpful to predict long-term ESRD in patients with AAV. Because a subgroup of critically ill patients with severe AAV present with deterioration of kidney function requiring RRT at admission, we here aimed to evaluate histopathological findings and predictive value of Berden's histopathological subgrouping and ARRS for severity of AKI and requirement of RRT during the short-term clinical course in critically ill patients requiring intensive care treatment and predictors for short-term renal recovery in patients requiring RRT. A subgroup of 15/46 (32. 6%) AAV patients with biopsy-proven AAV required RRT during the short-term course of disease, associated with requirement of critical care treatment. While histopathological subgrouping and ARRS were associated with requirement of acute RRT, presence of global glomerular scarring was the strongest predictor of failure to recover from RRT after initiation of remission induction therapy. This new aspect requires further investigation in a prospective controlled setting for therapeutic decision making especially in this subgroup.
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Affiliation(s)
- Samy Hakroush
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
| | - Desiree Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Peter Korsten
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Philipp Ströbel
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
| | - Michael Zeisberg
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany.,German Center for Cardiovascular Research (DZHK), Göttingen, Germany
| | - Björn Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
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Rhudy MB, Greenauer N, Mello C. Wearable light data logger for studying physiological and psychological effects of light data. HARDWAREX 2020; 8:e00157. [PMID: 35498234 PMCID: PMC9041241 DOI: 10.1016/j.ohx.2020.e00157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 10/26/2020] [Accepted: 10/26/2020] [Indexed: 05/21/2023]
Abstract
Light sensors can provide valuable information about environmental exposure; however, current light sensing packages are limited. This work presents the development of an open-source hardware device capable of logging light measurements. Due to its lightweight, wearable construction, it is well-suited to human subject research in naturalistic conditions. Its low cost makes it a viable option for population studies. This work offers an example application of objectively determining whether a person is indoors or outdoors based on the light measurements. This application has practical value within disciplines such as environmental and health psychology, which seek to relate psychological outcomes to environmental exposure.
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Affiliation(s)
- Matthew B Rhudy
- Mechanical Engineering, Division of Engineering, Business, and Computing, The Pennsylvania State University, Berks, Reading, PA 19610, USA
| | - Nathan Greenauer
- Applied Psychology, Division of Humanities, Arts, and Social Sciences, The Pennsylvania State University, Berks, Reading, PA 19610, USA
| | - Catherine Mello
- Applied Psychology, Division of Humanities, Arts, and Social Sciences, The Pennsylvania State University, Berks, Reading, PA 19610, USA
- Rehabilitation and Human Services, Division of Humanities, Arts, and Social Sciences, The Pennsylvania State University, Berks, Reading, PA 19610, USA
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19
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Felline A, Seeber M, Fanelli F. webPSN v2.0: a webserver to infer fingerprints of structural communication in biomacromolecules. Nucleic Acids Res 2020; 48:W94-W103. [PMID: 32427333 PMCID: PMC7319592 DOI: 10.1093/nar/gkaa397] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/21/2020] [Accepted: 05/17/2020] [Indexed: 12/25/2022] Open
Abstract
A mixed Protein Structure Network (PSN) and Elastic Network Model-Normal Mode Analysis (ENM-NMA)-based strategy (i.e. PSN-ENM) was developed to investigate structural communication in bio-macromolecules. Protein Structure Graphs (PSGs) are computed on a single structure, whereas information on system dynamics is supplied by ENM-NMA. The approach was implemented in a webserver (webPSN), which was significantly updated herein. The webserver now handles both proteins and nucleic acids and relies on an internal upgradable database of network parameters for ions and small molecules in all PDB structures. Apart from the radical restyle of the server and some changes in the calculation setup, other major novelties concern the possibility to: a) compute the differences in nodes, links, and communication pathways between two structures (i.e. network difference) and b) infer links, hubs, communities, and metapaths from consensus networks computed on a number of structures. These new features are useful to identify commonalties and differences between two different functional states of the same system or structural-communication signatures in homologous or analogous systems. The output analysis relies on 3D-representations, interactive tables and graphs, also available for download. Speed and accuracy make this server suitable to comparatively investigate structural communication in large sets of bio-macromolecular systems. URL: http://webpsn.hpc.unimore.it.
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Affiliation(s)
- Angelo Felline
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy
| | - Michele Seeber
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy
| | - Francesca Fanelli
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.,Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena 41125, Italy
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20
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Buechler SA, Stephens MT, Hummon AB, Ludwig K, Cannon E, Carter TC, Resnick J, Gökmen-Polar Y, Badve SS. ColoType: a forty gene signature for consensus molecular subtyping of colorectal cancer tumors using whole-genome assay or targeted RNA-sequencing. Sci Rep 2020; 10:12123. [PMID: 32694712 PMCID: PMC7374173 DOI: 10.1038/s41598-020-69083-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 07/03/2020] [Indexed: 01/02/2023] Open
Abstract
Colorectal cancer (CRC) tumors can be partitioned into four biologically distinct consensus molecular subtypes (CMS1-4) using gene expression. Evidence is accumulating that tumors in different subtypes are likely to respond differently to treatments. However, to date, there is no clinical diagnostic test for CMS subtyping. In this study, we used novel methodology in a multi-cohort training domain (n = 1,214) to develop the ColoType scores and classifier to predict CMS1-4 based on expression of 40 genes. In three validation cohorts (n = 1,744, in total) representing three distinct gene-expression measurement technologies, ColoType predicted gold-standard CMS subtypes with accuracies 0.90, 0.91, 0.88, respectively. To accommodate for potential intratumoral heterogeneity and tumors of mixed subtypes, ColoType was designed to report continuous scores measuring the prevalence of each of CMS1-4 in a tumor, in addition to specifying the most prevalent subtype. For analysis of clinical specimens, ColoType was also implemented with targeted RNA-sequencing (Illumina AmpliSeq). In a series of formalin-fixed, paraffin-embedded CRC samples (n = 49), ColoType by targeted RNA-sequencing agreed with subtypes predicted by two independent methods with accuracies 0.92, 0.82, respectively. With further validation, ColoType by targeted RNA-sequencing, may enable clinical application of CMS subtyping with widely-available and cost-effective technology.
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Affiliation(s)
- Steven A Buechler
- Department of Applied and Computational Mathematics and Statistics, Harper Cancer Research Institute, University of Notre Dame, 102B Crowley Hall, Notre Dame, IN, 46556, USA.
| | - Melissa T Stephens
- Genomics and Bioinformatics Core Facility, University of Notre Dame, Notre Dame, IN, USA
| | - Amanda B Hummon
- Department of Chemistry and Biochemistry, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Katelyn Ludwig
- Functional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Emily Cannon
- Department of Applied and Computational Mathematics and Statistics, Harper Cancer Research Institute, University of Notre Dame, 102B Crowley Hall, Notre Dame, IN, 46556, USA
| | - Tonia C Carter
- Center for Precision Medicine Research, Marshfield Clinic, Marshfield, WI, USA
| | - Jeffrey Resnick
- Department of Pathology, Marshfield Clinic, Marshfield, WI, USA
| | - Yesim Gökmen-Polar
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sunil S Badve
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.,Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA
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21
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Rhudy MB, Dreisbach SB, Moran MD, Ruggiero MJ, Veerabhadrappa P. Cut points of the Actigraph GT9X for moderate and vigorous intensity physical activity at four different wear locations. J Sports Sci 2019; 38:503-510. [PMID: 31865845 DOI: 10.1080/02640414.2019.1707956] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Accelerometer cut points are an important consideration for distinguishing the intensity of activity into categories such as moderate and vigorous. It is well-established in the literature that these cut points depend on a variety of factors, including age group, device, and wear location. The Actigraph GT9X is a newer model accelerometer that is used for physical activity research, but existing cut points for this device are limited since it is a newer device. Furthermore, there is not existing data on cut points for the GT9X at the ankle or foot locations, which offers some potential benefit for activities that do not involve arm and/or core motion. A total of N = 44 adults completed a four-stage treadmill protocol while wearing Actigraph GT9X sensors at four different locations: foot, ankle, wrist, and hip. Metabolic Equivalent of Task (MET) levels assessed by indirect calorimetry along with Receiver Operating Characteristic (ROC) curves were used to establish cut points for moderate and vigorous intensity for each wear location of the GT9X. Area under the ROC curves indicated high discrimination accuracy for each case.
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Affiliation(s)
- Matthew B Rhudy
- Engineering, Division of Engineering, Business, and Computing, The Pennsylvania State University, Reading, PA, USA
| | - Scott B Dreisbach
- Kinesiology, Division of Science, The Pennsylvania State University, Reading, PA, USA
| | - Matthew D Moran
- Kinesiology, Division of Science, The Pennsylvania State University, Reading, PA, USA
| | - Marissa J Ruggiero
- Kinesiology, Division of Science, The Pennsylvania State University, Reading, PA, USA
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22
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Use of the Electronic Health Record to Target Patients for Non-endoscopic Barrett's Esophagus Screening. Dig Dis Sci 2019; 64:3463-3470. [PMID: 31273597 PMCID: PMC7191846 DOI: 10.1007/s10620-019-05707-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 06/12/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND Clinical prediction models targeting patients for Barrett's esophagus (BE) screening include data obtained by interview, questionnaire, and body measurements. A tool based on electronic health records (EHR) data could reduce cost and enhance usability, particularly if combined with non-endoscopic BE screening methods. AIMS To determine whether EHR-based data can identify BE patients. METHODS We performed a retrospective review of patients ages 50-75 who underwent a first-time esophagogastroduodenoscopy. Data extracted from the EHR included demographics and BE risk factors. Endoscopy and pathology reports were reviewed for histologically confirmed BE. Screening criteria modified from clinical guidelines were assessed for association with BE. Subsequently, a score based on multivariate logistic regression was developed and assessed for its ability to identify BE subjects. RESULTS A total of 2931 patients were assessed, and BE was found in 1.9%. Subjects who met screening criteria were more likely to have BE (3.3% vs. 1.1%, p = 0.001), and the criteria predicted BE with an AUROC of 0.65 (95% CI 0.59-0.71). A score based on logistic regression modeling included gastroesophageal reflux disease, sex, body mass index, and ever-smoker status and identified BE subjects with an AUROC of 0.71 (95% CI 0.64-0.77). Both prediction tools produced higher AUROCs in women than in men. CONCLUSIONS EHR-based BE risk prediction tools identify BE patients with fair accuracy. While these tools may improve the efficiency of patient targeting for BE screening in the primary care setting, challenges remain to identify high-risk patients for non-invasive BE screening in clinical practice.
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23
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Luo H, Wang N, Huang L, Zhou X, Jin J, Li C, Wang D, Xu B, Xu J, Jiang L, Wang J, Cao Y, Xiao Y, Zhang Q, Mao X, Liu S, Chen L, Xiao M, Zhou J. Inflammatory signatures for quick diagnosis of life-threatening infection during the CAR T-cell therapy. J Immunother Cancer 2019; 7:271. [PMID: 31640816 PMCID: PMC6806557 DOI: 10.1186/s40425-019-0767-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 10/02/2019] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Chimeric antigen receptor-modified (CAR) T-cell immunotherapy is a novel promising therapy for treatment of B-cell malignancy. Cytokine release syndrome (CRS) and infection are the most common adverse events during CAR T-cell therapy. Similar clinical presentation of concurrent CRS and infection makes it difficult to differentially diagnose and timely treat the condition. METHODS We analyzed the features of infection events during the first 30 days after CAR T-cell infusion (CTI) in 109 patients from three clinical trials (ChiCTR-OPN-16008526, ChiCTR-OPC-16009113, ChiCTR-OPN-16009847). Based on the dynamic changes of interleukin (IL)-6 and ferritin, we proposed the "double peaks of IL-6" pattern as a feature of life-threatening infection during the first 30 days after CTI. Meanwhile, we screened candidate biomarkers from 70-biomarker panel to establish a prediction model for life-threatening infection. RESULTS In this study, 19 patients (17.4%) experienced a total of 19 infection events during the first 30 days after CAR T-cell infusion. Eleven patients (10.1%) had grade 4-5 infection, which were all bacterial infection and predominantly sepsis (N = 9). "Double peaks of IL-6" appeared in 9 out of 11 patients with life-threatening infection. The prediction model of three-cytokines (IL-8, IL-1β and interferon-γ) could predict life-threatening infection with high sensitivity (training: 100.0%; validation: 100.0%) and specificity (training: 97.6%; validation: 82.8%). On base of the aforementioned methods, we proposed a workflow for quick identification of life-threatening infection during CAR T-cell therapy. CONCLUSIONS In this study, we worked out two diagnostic methods for life-threatening infection during CAR T-cell therapy by analyzing inflammatory signatures, which contributed to reducing risks of infection-induced death.
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Affiliation(s)
- Hui Luo
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Na Wang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Liang Huang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Xiaoxi Zhou
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Jin Jin
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Chunrei Li
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Di Wang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Bin Xu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Jinhuan Xu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Lijun Jiang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Jue Wang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Yang Cao
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Yi Xiao
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Qian Zhang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Xia Mao
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Songya Liu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Liting Chen
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Min Xiao
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China
| | - Jianfeng Zhou
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. .,Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China.
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24
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Faron G, Balepa L, Parra J, Fils JF, Gucciardo L. The fetal fibronectin test: 25 years after its development, what is the evidence regarding its clinical utility? A systematic review and meta-analysis. J Matern Fetal Neonatal Med 2018; 33:493-523. [PMID: 29914277 DOI: 10.1080/14767058.2018.1491031] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background: The identification of women at risk for preterm birth should allow interventions which could improve neonatal outcome. Fetal fibronectin, a glycoprotein which acts normally as glue between decidua and amniotic membranes could be a good marker of impending labour when its concentration in cervicovaginal secretions between 22 and 36 weeks of gestation is ≥50 ng/mL. Many authors worldwide have tested this marker with many different methodologies and clinical settings, but conclusions about its clinical use are mixed. It is time for a comprehensive update through a systematic review and meta-analysis.Methods: We searched PubMed, Cochrane Library, and Embase, supplemented by manual search of bibliographies of known primary and review articles, international conference papers, and contact with experts from 1-1990 to 2-2018. We have selected all type of studies involving fetal fibronectin test accuracy for preterm delivery. Two authors independently extracted data about study characteristics and quality from identified publications. Contingency tables were constructed. Reference standards were preterm delivery before 37, 36, 35, 34, and 32 weeks, within 28, 21, 14, or 7 d and within 48 h. Data were pooled to produce summary likelihood ratios for positive and negative tests results.Results: One hundred and ninety-three primary studies were identified allowing analysis of 53 subgroups. In all settings, none of the summary likelihood ratios were >10 or <0.1, thus indicating moderate prediction, particularly in asymptomatic women and in multiple gestations.Conclusions: The fetal fibronectin test should not be used as a screening test for asymptomatic women. For high-risk asymptomatic women, and especially for women with multiple pregnancies, the performance of the fetal fibronectin test was also too low to be clinically relevant. Consensual use as a diagnostic tool for women with suspected preterm labor, the best use policy probably still depends on local contingencies, future cost-effectiveness analysis, and comparison with other more recent available biochemical markers.
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Affiliation(s)
- Gilles Faron
- Department of Obstetrics and Prenatal Medicine, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Lisa Balepa
- Department of Obstetrics and Prenatal Medicine, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - José Parra
- Department of Statistics, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | | | - Leonardo Gucciardo
- Department of Obstetrics and Prenatal Medicine, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
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25
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Park JE, Jeong GH, Lee IK, Yoon YR, Liu KH, Gu N, Shin KH. A Pharmacometabolomic Approach to Predict Response to Metformin in Early-Phase Type 2 Diabetes Mellitus Patients. Molecules 2018; 23:molecules23071579. [PMID: 29966242 PMCID: PMC6100517 DOI: 10.3390/molecules23071579] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Revised: 06/22/2018] [Accepted: 06/28/2018] [Indexed: 12/14/2022] Open
Abstract
Metformin is a first-line medication for type 2 diabetes mellitus (T2DM). Based on its universal use, the consideration of inter-individual variability and development of predictive biomarkers are clinically significant. We aimed to identify endogenous markers of metformin responses using a pharmacometabolomic approach. Twenty-nine patients with early-phase T2DM were enrolled and orally administered metformin daily for 6 months. A total of 22 subjects were included in the final analysis. Patients were defined as responders or non-responders based on changes in their glycated haemoglobin A1c (HbA1c) from baseline, over 3 months. Urine metabolites at baseline, as well as at the 3 and 6 month follow-ups after the start of treatment were analysed using gas chromatography-mass spectrometry and evaluated with multivariate analyses. Metabolites distinguishable between the two response groups were obtained at baseline, as well as at the 3 and 6 month follow-ups, and significantly different metabolites were listed as markers of metformin response. Among the identified metabolites, citric acid, myoinositol, and hippuric acid levels showed particularly significant differences between the non-responder and responder groups. We thus identified different metabolite profiles in the two groups of T2DM patients after metformin administration, using pharmacometabolomics. These results might facilitate a better understanding and prediction of metformin response and its variability in individual patients.
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Affiliation(s)
- Jeong-Eun Park
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.
| | - Gui-Hwa Jeong
- Department of Endocrinology, Changwon Fatima Hospital, Changwon 51394, Korea.
| | - In-Kyu Lee
- Department of Endocrinology, Kyungpook National University Hospital, Daegu 41944, Korea.
| | - Young-Ran Yoon
- Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Cell and Matrix Research Institute and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu 41944, Korea.
| | - Kwang-Hyeon Liu
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.
| | - Namyi Gu
- Department of Clinical Pharmacology and Therapeutics, Clinical Trial Center, Dongguk University College of Medicine and Ilsan Hospital, Goyang 10326, Korea.
| | - Kwang-Hee Shin
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.
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Exploring Demographics and Health as Predictors of Risk-Taking in UK Help-Seeking Veterans. Healthcare (Basel) 2018; 6:healthcare6020058. [PMID: 29874783 PMCID: PMC6023507 DOI: 10.3390/healthcare6020058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 11/16/2022] Open
Abstract
Risk-taking amongst veterans has severe consequences, yet few studies have examined factors that may predict risk-taking in help-seeking veteran populations. This paper presents a cross-sectional study involving a random sample of 667 UK help-seeking veterans, investigating the role of demographics, mental health and physical health presentations on the propensity for risk-taking. Out of 403 (73.4%) veterans, 350 (86.8%) reported risk-taking in the past month. We found that younger age, being in a relationship, probable PTSD, common mental health difficulties and traumatic brain injury were significantly associated with risk-taking. Additionally, a direct association was found between increased risk-taking and PTSD symptom clusters, including higher hyperarousal, elevated negative alterations in mood and cognition. Our findings provide initial evidence for demographic and mental health presentations as predictors of risk-taking in help-seeking veterans. Further research and longitudinal studies are needed to facilitate valid risk assessments, and early intervention for veteran services.
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28
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Spatial gene expression analysis of neuroanatomical differences in mouse models. Neuroimage 2017; 163:220-230. [PMID: 28882630 DOI: 10.1016/j.neuroimage.2017.08.065] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Revised: 08/08/2017] [Accepted: 08/29/2017] [Indexed: 02/06/2023] Open
Abstract
MRI is a powerful modality to detect neuroanatomical differences that result from mutations and treatments. Knowing which genes drive these differences is important in understanding etiology, but candidate genes are often difficult to identify. We tested whether spatial gene expression data from the Allen Brain Institute can be used to inform us about genes that cause neuroanatomical differences. For many single-gene-mutation mouse models, we found that affected neuroanatomy was not strongly associated with the spatial expression of the altered gene and there are specific caveats for each model. However, among models with significant neuroanatomical differences from their wildtype controls, the mutated genes had preferential spatial expression in affected neuroanatomy. In mice exposed to environmental enrichment, candidate genes could be identified by a genome-wide search for genes with preferential spatial expression in the altered neuroanatomical regions. These candidates have functions related to learning and plasticity. We demonstrate that spatial gene expression of single-genes is a poor predictor of altered neuroanatomy, but altered neuroanatomy can identify candidate genes responsible for neuroanatomical phenotypes.
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29
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Tang Y, Shen J, Zhang F, Zhou X, Tang Z, You T. Scoring systems used to predict mortality in patients with acute upper gastrointestinal bleeding in the ED. Am J Emerg Med 2017; 36:27-32. [PMID: 28673695 DOI: 10.1016/j.ajem.2017.06.053] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 06/24/2017] [Accepted: 06/25/2017] [Indexed: 01/29/2023] Open
Abstract
OBJECTIVE Acute upper gastrointestinal bleeding (UGIB) is a potentially life-threatening condition that requires rapid assessment in the emergency department (ED). We aimed to compare the performance of the AIMS65, Glasgow-Blatchford (Blatchford), preendoscopic Rockall (pre-Rockall), and preendoscopic Baylor bleeding (pre-Baylor) scores in predicting 30-day mortality in patients with acute UGIB in the ED setting. METHODS Consecutive patients with acute UGIB who were admitted to the ED ward during 2012-2016 were retrospectively recruited. Data were retrieved from the admission list of the ED using international classification of disease codes via computer registration. The predictive accuracy of these four scores was compared using the area under the receiver operating characteristic curve (AUC) method. RESULTS Among the 395 patients included during the study period, the total 30-day mortality rate was 10.4% (41/395). The AIMS65 and Glasgow-Blatchford scores performed better with an AUC of 0.907 (95% confidence interval (CI), 0.852-0.963; P<0.001) and 0.870 (95% confidence interval, 0.833-0.902; P<0.001) compared with other scoring systems (preendoscopic Rockall score: AUC, 0.709; 95% CI, 0.635-0.784; P<0.001; preendoscopic Baylor score: AUC, 0.523; 95% CI, 0.472-0.573; P>0.05). CONCLUSION In patients with acute UGIB in the ED, the AIMS65 and Glasgow-Blatchford scores are clinically more useful for predicting 30-day mortality than the preendoscopic Rockall and preendoscopic Baylor scores. The AIMS65 score might be more ideal for risk stratification in the ED setting.
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Affiliation(s)
- Yuedong Tang
- Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai, China
| | - Jie Shen
- Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai, China.
| | - Feng Zhang
- Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai, China
| | - Xiaoyong Zhou
- Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai, China
| | - Zhongyan Tang
- Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai, China
| | - Tingting You
- Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai, China
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Diaz KM, Krupka DJ, Chang MJ, Kronish IM, Moise N, Goldsmith J, Schwartz JE. Wrist-based cut-points for moderate- and vigorous-intensity physical activity for the Actical accelerometer in adults. J Sports Sci 2017; 36:206-212. [PMID: 28282744 DOI: 10.1080/02640414.2017.1293279] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Wrist-based accelerometers are increasingly used to assess physical activity (PA) in population-based studies; however, cut-points to translate wrist-based accelerometer counts into PA intensity categories are still needed. The purpose of this study was to determine wrist-based cut-points for moderate- and vigorous-intensity ambulatory PA in adults for the Actical accelerometer. Healthy adults (n = 24) completed a four-phase treadmill exercise protocol (1.9, 3.0, 4.0 and 5.2 mph) while wearing an Actical accelerometer on their wrist. Metabolic equivalent of task (MET) levels were assessed by indirect calorimetry. Receiver operating characteristics (ROC) curves were generated to determine accelerometer counts that maximised sensitivity and specificity for classification of moderate (≥3 METs) and vigorous (>6 METs) ambulatory activity. The area under the ROC curves to discriminate moderate- and vigorous-intensity ambulatory activity were 0.93 (95% confidence interval [CI]: 0.90-0.97; P < 0.001) and 0.96 (95% CI: 0.94-0.99; P < 0.001), respectively. The identified cut-point for moderate-intensity ambulatory activity was 1031 counts per minute, which had a corresponding sensitivity and specificity of 85.6% and 87.5%, respectively. The identified cut-point for vigorous intensity ambulatory activity was 3589 counts per minute, which had a corresponding sensitivity and specificity of 88.0% and 98.7%, respectively. This study established intensity-specific cut-points for wrist-based wear of the Actical accelerometer which are recommended for quantification of moderate- and vigorous-intensity ambulatory activity.
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Affiliation(s)
- Keith M Diaz
- a Center for Behavioral Cardiovascular Health, Department of Medicine , Columbia University Medical Center , New York , NY , USA
| | - David J Krupka
- a Center for Behavioral Cardiovascular Health, Department of Medicine , Columbia University Medical Center , New York , NY , USA
| | - Melinda J Chang
- a Center for Behavioral Cardiovascular Health, Department of Medicine , Columbia University Medical Center , New York , NY , USA
| | - Ian M Kronish
- a Center for Behavioral Cardiovascular Health, Department of Medicine , Columbia University Medical Center , New York , NY , USA
| | - Natalie Moise
- a Center for Behavioral Cardiovascular Health, Department of Medicine , Columbia University Medical Center , New York , NY , USA
| | - Jeff Goldsmith
- b Department of Biostatistics, Mailman School of Public Health , Columbia University , New York , NY , USA
| | - Joseph E Schwartz
- a Center for Behavioral Cardiovascular Health, Department of Medicine , Columbia University Medical Center , New York , NY , USA.,c Department of Psychiatry , Stony Brook University , Stony Brook , NY , USA
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Liu T, Han Y, Tang L, Wu J, Miao Y, Gao B, Shang J. Detection of chronic brain damage by diffusion-weighted imaging with multiple b values in patients with type 2 diabetes. Medicine (Baltimore) 2016; 95:e4726. [PMID: 27583912 PMCID: PMC5008596 DOI: 10.1097/md.0000000000004726] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The aim of the study was to evaluate the performance of parameters obtained from diffusion-weighted imaging (DWI) with multiple b values in the detection of chronic brain damage in patients with type 2 diabetes.We enrolled 30 patients with or without abnormalities on brain magnetic resonance imaging (lacunar infarction, leukoaraiosis, and/or brain atrophy) and 15 nondiabetic controls; obtained DWI parameters that included apparent diffusion coefficient (ADC), fast ADC (ADCfast), slow ADC (ADCslow), fraction of fast ADC (f), distributed diffusion coefficient (DDC), and stretched exponential (α); and performed receiver operating characteristic (ROC) analysis to evaluate the performance of parameters for the detection of chronic brain damage.The parameters ADC, ADCslow, f, and DDC were increased, whereas parameters ADCfast and α were decreased in type 2 diabetes patients compared with controls without diabetes. The centrum semiovale showed the most significant change in the evaluated parameters, and the changes in parameters ADCslow, f, and DDC were greater than the changes in other parameters. There was no significance between parameters of the biexponential model (ADCfast, ADCslow, f) and parameters of the stretched model (DDC, α), but parameters of both these models were superior to the parameter of monoexponential model (ADC). Moreover, ROC analysis showed that ADCslow of the centrum semiovale supplied by the anterior cerebral artery had the highest performance for detection of chronic brain damage (area under the ROC curve of 0.987, 93.3% sensitivity, and 100% specificity).Our study shows that DWI with multiple b values can quantitatively access chronic brain damage and may be used for detection and monitoring in type 2 diabetes patients.
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Affiliation(s)
- Tieli Liu
- Department of Radiology, First Affiliated Hospital
- Graduate School, Dalian Medical University
| | - Yunpeng Han
- Department of Radiology, Dalian Municipal Third People's Hospital
| | - Lemei Tang
- Department of Radiology, First Affiliated Hospital
| | - Jianlin Wu
- Department of Radiology, Affiliated Zhongshan Hospital, Dalian University, Liaoning Province, China
- Correspondence: Jianlin Wu, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China (e-mail: ); Yanwei Miao, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China (e-mail: )
| | - Yanwei Miao
- Department of Radiology, First Affiliated Hospital
- Correspondence: Jianlin Wu, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China (e-mail: ); Yanwei Miao, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China (e-mail: )
| | - Bingbing Gao
- Department of Radiology, First Affiliated Hospital
| | - Jin Shang
- Department of Radiology, First Affiliated Hospital
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López-Ratón M, Cadarso-Suárez C, Molanes-López EM, Letón E. Confidence intervals for the symmetry point: an optimal cutpoint in continuous diagnostic tests. Pharm Stat 2016; 15:178-92. [DOI: 10.1002/pst.1734] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 11/10/2015] [Accepted: 11/23/2015] [Indexed: 11/06/2022]
Affiliation(s)
- Mónica López-Ratón
- Biostatistics Unit, Department of Statistics and Operations Research; USC; San Francisco s/n Santiago de Compostela 15782 Spain
| | - Carmen Cadarso-Suárez
- Biostatistics Unit, Department of Statistics and Operations Research; USC; San Francisco s/n Santiago de Compostela 15782 Spain
| | - Elisa M. Molanes-López
- Biostatistics Section, Department of Statistics and Operations Research; UCM; Plaza Ramón y Cajal s/n Madrid 28040 Spain
| | - Emilio Letón
- Department of Artificial Intelligence; UNED; C/ Juan del Rosal 16 Madrid 28040 Spain
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Doebler P, Holling H. Meta-analysis of Diagnostic Accuracy and ROC Curves with Covariate Adjusted Semiparametric Mixtures. PSYCHOMETRIKA 2015; 80:1084-1104. [PMID: 25361619 DOI: 10.1007/s11336-014-9430-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Indexed: 06/04/2023]
Abstract
Many screening tests dichotomize a measurement to classify subjects. Typically a cut-off value is chosen in a way that allows identification of an acceptable number of cases relative to a reference procedure, but does not produce too many false positives at the same time. Thus for the same sample many pairs of sensitivities and false positive rates result as the cut-off is varied. The curve of these points is called the receiver operating characteristic (ROC) curve. One goal of diagnostic meta-analysis is to integrate ROC curves and arrive at a summary ROC (SROC) curve. Holling, Böhning, and Böhning (Psychometrika 77:106-126, 2012a) demonstrated that finite semiparametric mixtures can describe the heterogeneity in a sample of Lehmann ROC curves well; this approach leads to clusters of SROC curves of a particular shape. We extend this work with the help of the [Formula: see text] transformation, a flexible family of transformations for proportions. A collection of SROC curves is constructed that approximately contains the Lehmann family but in addition allows the modeling of shapes beyond the Lehmann ROC curves. We introduce two rationales for determining the shape from the data. Using the fact that each curve corresponds to a natural univariate measure of diagnostic accuracy, we show how covariate adjusted mixtures lead to a meta-regression on SROC curves. Three worked examples illustrate the method.
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Affiliation(s)
- Philipp Doebler
- Institut für Psychologie, Westfälische Wilhelms-Universität, Fliednerstr. 21, 48149 , Münster, Germany.
| | - Heinz Holling
- Institut für Psychologie, Westfälische Wilhelms-Universität, Fliednerstr. 21, 48149 , Münster, Germany.
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Abstract
The Youden Index is a summary measurement of the receiver operating characteristic (ROC) curve for the accuracy of a diagnostic test with ordinal or continuous endpoints. The bootstrap confidence interval based on the adjusted proportion estimate was shown to have satisfactory performance among the existing confidence intervals, including the parametric interval via the delta method. In this article, we propose two confidence intervals using the square-and-add limits based on the Wilson score method. We compare the two proposed intervals with the existing interval with extensive simulation studies. The new interval based on the empirical proportion estimate generally has better performance than that based on the adjusted proportion estimate. A real example from a clinical trial of prostate cancer is illustrated for the application of the new intervals.
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Affiliation(s)
- Guogen Shan
- Epidemiology and Biostatistics Program, Department of Environmental and Occupational Health School of Community Health Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USA
- * E-mail:
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Suhre K, Schwartz JE, Sharma VK, Chen Q, Lee JR, Muthukumar T, Dadhania DM, Ding R, Ikle DN, Bridges ND, Williams NM, Kastenmüller G, Karoly ED, Mohney RP, Abecassis M, Friedewald J, Knechtle SJ, Becker YT, Samstein B, Shaked A, Gross SS, Suthanthiran M. Urine Metabolite Profiles Predictive of Human Kidney Allograft Status. J Am Soc Nephrol 2015; 27:626-36. [PMID: 26047788 DOI: 10.1681/asn.2015010107] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 04/15/2015] [Indexed: 12/29/2022] Open
Abstract
Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.
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Affiliation(s)
- Karsten Suhre
- Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Joseph E Schwartz
- Department of Psychiatry, Stony Brook University, Stony Brook, New York; Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - Vijay K Sharma
- Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - Qiuying Chen
- Department of Pharmacology, Weill Cornell College of Medicine, New York, New York
| | - John R Lee
- Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - Thangamani Muthukumar
- Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - Darshana M Dadhania
- Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - Ruchuang Ding
- Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - David N Ikle
- Rho Federal Systems, Chapel Hill, North Carolina
| | - Nancy D Bridges
- National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
| | - Nikki M Williams
- National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
| | - Gabi Kastenmüller
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | | | | | - Michael Abecassis
- Division of Surgery-Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - John Friedewald
- Division of Nephrology-Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Stuart J Knechtle
- Division of Surgery, Department of Surgery, University of Wisconsin Hospitals and Clinics, Madison, Wisconsin
| | - Yolanda T Becker
- Division of Surgery, Department of Surgery, University of Wisconsin Hospitals and Clinics, Madison, Wisconsin
| | - Benjamin Samstein
- Division of Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York; and
| | - Abraham Shaked
- Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Steven S Gross
- Department of Pharmacology, Weill Cornell College of Medicine, New York, New York
| | - Manikkam Suthanthiran
- Division of Nephrology and Hypertension, Departments of Medicine and Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York;
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Shi LF. How "proficient" is proficient? Bilingual listeners' recognition of English words in noise. Am J Audiol 2015; 24:53-65. [PMID: 25551364 DOI: 10.1044/2014_aja-14-0041] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 11/21/2014] [Indexed: 11/09/2022] Open
Abstract
PURPOSE Shi (2011, 2013) obtained sensitivity/specificity measures of bilingual listeners' English and relative proficiency ratings as the predictor of English word recognition in quiet. The current study investigated how relative proficiency predicted word recognition in noise. METHOD Forty-two monolingual and 168 bilingual normal-hearing listeners were included. Bilingual listeners rated their proficiency in listening, speaking, and reading in English and in the other language using an 11-point scale. Listeners were presented with 50 English monosyllabic words in quiet at 45 dB HL and in multitalker babble with a signal-to-noise ratio of +6 and 0 dB. RESULTS Data in quiet confirmed Shi's (2013) finding that relative proficiency with or without dominance predicted well whether bilinguals performed on par with the monolingual norm. Predicting the outcome was difficult for the 2 noise conditions. To identify bilinguals whose performance fell below the normative range, dominance per se or a combination of dominance and average relative proficiency rating yielded the best sensitivity/specificity and summary measures, including Youden's index. CONCLUSION Bilinguals' word recognition is more difficult to predict in noise than in quiet; however, proficiency and dominance variables can predict reasonably well whether bilinguals may perform at a monolingual normative level.
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Lee JR, Muthukumar T, Dadhania D, Ding R, Sharma VK, Schwartz JE, Suthanthiran M. Urinary cell mRNA profiles predictive of human kidney allograft status. Immunol Rev 2015; 258:218-40. [PMID: 24517436 DOI: 10.1111/imr.12159] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Kidney allograft status is currently characterized using the invasive percutaneous needle core biopsy procedure. The procedure has become safer over the years, but challenges and complications still exist including sampling error, interobserver variability, bleeding, arteriovenous fistula, graft loss, and even death. Because the most common type of acute rejection is distinguished by inflammatory cells exiting the intravascular compartment and gaining access to the renal tubular space, we reasoned that a kidney allograft may function as an in vivo flow cytometer and sort cells involved in rejection into urine. To test this idea, we developed quantitative polymerase chain reaction (PCR) assays for absolute quantification of mRNA and pre-amplification protocols to overcome the low RNA yield from urine. Here, we review our single center urinary cell mRNA profiling studies that led to the multicenter Clinical Trials in Organ Transplantation (CTOT-04) study and the discovery and validation of a 3-gene signature of 18S rRNA-normalized measures of CD3ε mRNA and IP-10 mRNA and 18S rRNA that is diagnostic and predictive of acute cellular rejection in the kidney allograft. We also review our development of a 4-gene signature of mRNAs for vimentin, NKCC2, E-cadherin, and 18S rRNA diagnostic of interstitial fibrosis/tubular atrophy (IF/TA).
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Affiliation(s)
- John R Lee
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
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Hughes G. Youden's index and the weight of evidence. Methods Inf Med 2015; 54:198-9. [PMID: 25658987 DOI: 10.3414/me14-04-0003] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 01/22/2015] [Indexed: 11/09/2022]
Abstract
By means of Shannon's relationship between information and probability, Youden's index for rating diagnostic tests is shown to be a probability-scale analogue of the log-likelihood ratio of a positive test outcome.
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Affiliation(s)
- G Hughes
- Dr. Gareth Hughes, SRUC, The King's Buildings, West Mains Road Edinburgh EH9 3JG, UK, E-mail:
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Carvalho T, Pinto-Gouveia J, Cunha M, Duarte J. Portuguese version of the PTSD Checklist-Military Version (PCL-M) - II: diagnostic utility. REVISTA BRASILEIRA DE PSIQUIATRIA 2014; 37:55-62. [DOI: 10.1590/1516-4446-2013-1319] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Accepted: 02/19/2014] [Indexed: 11/22/2022]
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Charoensawat S, Böhning W, Böhning D, Holling H. Meta-analysis and meta-modelling for diagnostic problems. BMC Med Res Methodol 2014; 14:56. [PMID: 24758534 PMCID: PMC4007022 DOI: 10.1186/1471-2288-14-56] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 04/14/2014] [Indexed: 11/11/2023] Open
Abstract
BACKGROUND A proportional hazards measure is suggested in the context of analyzing SROC curves that arise in the meta-analysis of diagnostic studies. The measure can be motivated as a special model: the Lehmann model for ROC curves. The Lehmann model involves study-specific sensitivities and specificities and a diagnostic accuracy parameter which connects the two. METHODS A study-specific model is estimated for each study, and the resulting study-specific estimate of diagnostic accuracy is taken as an outcome measure for a mixed model with a random study effect and other study-level covariates as fixed effects. The variance component model becomes estimable by deriving within-study variances, depending on the outcome measure of choice. In contrast to existing approaches - usually of bivariate nature for the outcome measures - the suggested approach is univariate and, hence, allows easily the application of conventional mixed modelling. RESULTS Some simple modifications in the SAS procedure proc mixed allow the fitting of mixed models for meta-analytic data from diagnostic studies. The methodology is illustrated with several meta-analytic diagnostic data sets, including a meta-analysis of the Mini-Mental State Examination as a diagnostic device for dementia and mild cognitive impairment. CONCLUSIONS The proposed methodology allows us to embed the meta-analysis of diagnostic studies into the well-developed area of mixed modelling. Different outcome measures, specifically from the perspective of whether a local or a global measure of diagnostic accuracy should be applied, are discussed as well. In particular, variation in cut-off value is discussed together with recommendations on choosing the best cut-off value. We also show how this problem can be addressed with the proposed methodology.
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Affiliation(s)
| | - Walailuck Böhning
- Statistics and Quantitative Methods, Faculty of Psychology and Sport Science, University of Münster, Münster, Germany
| | - Dankmar Böhning
- Southampton Statistical Sciences Research Institute, Mathematics and Medical Statistics, University of Southampton, Southampton SO17 1BJ, UK
| | - Heinz Holling
- Statistics and Quantitative Methods, Faculty of Psychology and Sport Science, University of Münster, Münster, Germany
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Bürkner PC, Doebler P. Testing for publication bias in diagnostic meta-analysis: a simulation study. Stat Med 2014; 33:3061-77. [PMID: 24753050 DOI: 10.1002/sim.6177] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Revised: 03/06/2014] [Accepted: 03/27/2014] [Indexed: 12/18/2022]
Abstract
The present study investigates the performance of several statistical tests to detect publication bias in diagnostic meta-analysis by means of simulation. While bivariate models should be used to pool data from primary studies in diagnostic meta-analysis, univariate measures of diagnostic accuracy are preferable for the purpose of detecting publication bias. In contrast to earlier research, which focused solely on the diagnostic odds ratio or its logarithm ( ln ω), the tests are combined with four different univariate measures of diagnostic accuracy. For each combination of test and univariate measure, both type I error rate and statistical power are examined under diverse conditions. The results indicate that tests based on linear regression or rank correlation cannot be recommended in diagnostic meta-analysis, because type I error rates are either inflated or power is too low, irrespective of the applied univariate measure. In contrast, the combination of trim and fill and ln ω has non-inflated or only slightly inflated type I error rates and medium to high power, even under extreme circumstances (at least when the number of studies per meta-analysis is large enough). Therefore, we recommend the application of trim and fill combined with ln ω to detect funnel plot asymmetry in diagnostic meta-analysis.
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Classification criteria for distinguishing cortisol responders from nonresponders to psychosocial stress: evaluation of salivary cortisol pulse detection in panel designs. Psychosom Med 2013; 75:832-40. [PMID: 24184845 DOI: 10.1097/psy.0000000000000002] [Citation(s) in RCA: 273] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Hypothalamic-pituitary-adrenal axis reactivity to acute stimulation is frequently assessed by repeated sampling of salivary cortisol. Researchers often strive to distinguish between individuals who show (responders) and those do not show (nonresponders) cortisol responses. For this, fixed threshold classification criteria, such as a 2.5-nmol/l baseline-to-peak increase, are frequently used. However, the performance of such criteria has not been systematically evaluated. METHODS Repeated salivary cortisol data from 504 participants exposed to either the Trier Social Stress Test (TSST; n = 309) or a placebo protocol (n = 195) were used for analyses. To obtain appropriate classifications of cortisol responders versus nonresponders, a physiologically plausible, autoregressive latent trajectory (ALT) mixture model was fitted to these data. Response classifications according to the ALT model and information on the experimental protocol (TSST versus placebo TSST) were then used to evaluate the performance of different proposed classifier proxies by receiver operating characteristics. RESULTS Moment structure of cortisol time series was adequately accounted for by the proposed ALT model. The commonly used 2.5-nmol/l criterion was found to be overly conservative, resulting in a high rate of 16.5% false-negative classifications. Lowering this criterion to 1.5 nmol/l or using a percentage baseline-to-peak increase of 15.5% as a threshold yielded improved performance (39.3% and 26.7% less misclassifications, respectively). CONCLUSIONS Alternative classification proxies (1.5 nmol/l or 15.5% increase) are able to effectively distinguish between cortisol responders and nonresponders and should be used in future research, whenever statistical response class allocation is not feasible.
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Moore Simas TA, Crawford SL, Bathgate S, Yan J, Robidoux L, Moore M, Maynard SE. Angiogenic biomarkers for prediction of early preeclampsia onset in high-risk women. J Matern Fetal Neonatal Med 2013; 27:1038-48. [PMID: 24066977 DOI: 10.3109/14767058.2013.847415] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Chronic hypertension, pregestational diabetes mellitus, history of prior preeclampsia and obese nulliparity are maternal conditions associated with increased preeclampsia risk. Whether altered maternal angiogenic factor levels allow for prediction of pending disease is unclear. Our objective was to evaluate angiogenic factors for early preeclampsia prediction in high-risk women. METHODS Serial serum specimens were collected from 157 women at high preeclampsia risk and 50 low-risk controls between 23 and 36 weeks gestation in 3 windows (23-27.6, 28-31.6, and 32-35.6 weeks) in a two-center observational cohort. Soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) were measured by ELISA. RESULTS Multivariate parsimonious logistic regression analyses using backward elimination for prediction of early-preeclampsia (diagnosed < 34 weeks) found the best-fitting model included the predictors (1) sFlt1 measured in the second window (28-31.6 weeks) with AUC 0.85, sensitivity 67% and specificity 96% and (2) sFlt1 measured in the first window (23-27.6 weeks) and sEng change between first and second window with AUC 0.91, sensitivity 86% and specificity 96%. CONCLUSIONS Two-stage sampling screening protocol utilizing sFlt1 and sEng is promising for prediction of preeclampsia diagnosed before 34 weeks. Larger studies are needed to confirm these findings.
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Affiliation(s)
- Tiffany A Moore Simas
- Department of Obstetrics and Gynecology, University of Massachusetts Medical School/UMass Memorial Health Care , Worcester, MA , USA
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Suthanthiran M, Schwartz JE, Ding R, Abecassis M, Dadhania D, Samstein B, Knechtle SJ, Friedewald J, Becker YT, Sharma VK, Williams NM, Chang CS, Hoang C, Muthukumar T, August P, Keslar KS, Fairchild RL, Hricik DE, Heeger PS, Han L, Liu J, Riggs M, Ikle DN, Bridges ND, Shaked A. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med 2013; 369:20-31. [PMID: 23822777 PMCID: PMC3786188 DOI: 10.1056/nejmoa1215555] [Citation(s) in RCA: 269] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. METHODS We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. RESULTS A three-gene signature of 18S ribosomal (rRNA)-normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operating-characteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer-Lemeshow test indicated good fit (P=0.77). In an external-validation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P=0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti-interleukin-2 receptor antibodies from those who received T-cell-depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P=0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). CONCLUSIONS A molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts. (Funded by the National Institutes of Health and others.).
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Silva Júnior JDA, Camisasca DR, Bernardo V, Ribeiro GS, Dias FL, de Faria PAS, de Amorim LMDF, Lourenço SQC. The significance of p53 immunoexpression with different clones (DO-7 and PAb-240) in oral squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 2013; 75:82-90. [PMID: 23817043 DOI: 10.1159/000349978] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 01/30/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIM The TP53 gene is a tumor suppressor gene. Its product is a nuclear protein that regulates cell cycle arrest, apoptosis and DNA repair. Anti-p53 clones DO-7 and PAb-240 recognize the amino acid sequences 21-25 and 213-217, respectively. This study aimed to evaluate the expression of these clones and their relationship with clinicopathological features and survival analysis in oral squamous cell carcinomas (OSCC). METHODS Information on 53 primary OSCC was collected at the Brazilian National Cancer Institute. An immunohistochemical method was applied to evaluate p53 expression (DO-7 and PAb-240). Their expression was analyzed quantitatively and correlated with clinicopathological features. Kaplan-Meier survival curves and log rank test were used. RESULTS Immunopositivity for DO-7 was present in 64% of the cases, while 58% were positive for PAb-240. There was no correlation between immunoexpression of both antibodies and clinicopathological features or survival analysis. DO-7 expression was significantly higher (p = 0.001) than that of PAb-240. CONCLUSIONS There were quantitative differences between the expression of the antibodies studied, which may reflect a different specificity of each one. To confirm immunohistochemical results and estimate the true prognostic role of TP53 in OSCC, it is important to perform mutation analysis.
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Goh EY, Chua SY, Hong SJ, Ng SS. Reliability and concurrent validity of Four Square Step Test scores in subjects with chronic stroke: a pilot study. Arch Phys Med Rehabil 2013; 94:1306-11. [PMID: 23416218 DOI: 10.1016/j.apmr.2013.01.027] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2012] [Revised: 01/21/2013] [Accepted: 01/30/2013] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To establish (1) the intrarater and interrater reliability of Four Square Step Test (FSST) times in persons with chronic stroke; (2) the concurrent validity of FSST times with standing balance and functional mobility measures; and (3) the FSST cutoff score for distinguishing the differences in dynamic balance performance of persons with chronic stroke from healthy control adults. DESIGN Cross-sectional study. SETTING University-based rehabilitation center. PARTICIPANTS Convenience sample of subjects (N=30) consisting of community-dwelling persons with chronic stroke (n=15) and healthy control adults (n=15). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES FSST scores; balance and functional mobility measured using Berg Balance Scale (BBS) scores; Timed Up & Go (TUG) test scores; and limits of stability (LOS) measured by dynamic posturography. RESULTS FSST times showed good intrarater reliability, with intraclass correlation coefficients ranging from .82 to .83 and an interrater reliability >.99. An FSST cutoff score of 11 seconds was able to discriminate between healthy adults older than 50 years and persons with stroke (sensitivity, 73.3%; specificity, 93.3%). FSST times were correlated with LOS scores for directional control in the backward direction (r=.64; P=.01). FSST was approaching a significant correlation with TUG scores (r=.59; P=.02) and LOS scores for endpoint excursion in the forward direction (r=-.58; P=.02). However, there was no correlation with BBS scores. CONCLUSION FSST is an easy-to-administer clinical test with good intrarater and interrater reliability in persons with chronic stroke to assess dynamic standing balance. FSST times of 11 seconds are able to differentiate between persons with chronic stroke and healthy adults older than 50 years. The correlation of FSST times with standing balance and functional mobility measures requires further research with a larger sample size.
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Affiliation(s)
- Esther Y Goh
- Department of Physiotherapy, Tan Tock Seng Hospital, Singapore
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Affiliation(s)
- Haochuan Zhou
- a Department of Mathematics and Statistics , Georgia State University , Atlanta , Georgia , USA
| | - Gengsheng Qin
- a Department of Mathematics and Statistics , Georgia State University , Atlanta , Georgia , USA
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Holling H, Böhning W, Böhning D. Meta-analysis of diagnostic studies based upon SROC-curves: a mixed model approach using the Lehmann family. STAT MODEL 2012. [DOI: 10.1177/1471082x1201200403] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Meta-analysis of diagnostic studies experiences the common problem that different studies might not be comparable since they have been using a different cut-off value for the continuous or ordered categorical diagnostic test value defining different regions for which the diagnostic test is defined to be positive. Hence specificities and sensitivities arising from different studies might vary just because the underlying cut-off value had been different. To cope with the cut-off value problem, interest is usually directed towards the receiver operating characteristic (ROC) curve which consists of pairs of sensitivities and false positive rate (1–specificity). In the context of meta-analysis, one pair represents one study and the associated diagram is called SROC curve where the S stands for ‘summary’. The paper will consider—as a novel approach—modelling SROC curves with the Lehmann family that assumes log-sensitivity is proportional to the log-false positive rate across studies. The approach allows for study-specific false positive rates which are treated as (infinitely many) nuisance parameters and eliminated by means of the profile likelihood. The adjusted profile likelihood turns out to have a simple univariate Gaussian structure which is ultimately used for building inference for the parameter of the Lehmann family. The Lehmann model is further extended by allowing the constant of proportionality to vary across studies to cope with unobserved heterogeneity. The simple Gaussian form of the adjusted profile likelihood allows this extension easily as a form of a mixed model in which unobserved heterogeneity is incorporated by means of a normal random effect. Some meta-analytic applications on diagnostic studies including brain natriuretic peptides for heart failure, alcohol use disorder identification test (AUDIT) and the consumption part of AUDIT for detection of unhealthy alcohol use as well as the mini-mental state examination for cognitive disorders are discussed to illustrate the methodology.
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Affiliation(s)
- Heinz Holling
- Statistics and Quantitative Methods, University of Münster, Münster, Germany
| | - Walailuck Böhning
- Statistics and Quantitative Methods, University of Münster, Münster, Germany
| | - Dankmar Böhning
- Southampton Statistical Sciences Research Institute, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK
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Lindenblatt RDCR, Martinez GL, Silva LE, Faria PS, Camisasca DR, Lourenço SDQC. Oral squamous cell carcinoma grading systems--analysis of the best survival predictor. J Oral Pathol Med 2011; 41:34-9. [PMID: 21902722 DOI: 10.1111/j.1600-0714.2011.01068.x] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
BACKGROUND The TNM system has been used for decades in an attempt to predict clinical behavior and appropriate therapy for oral squamous cell carcinomas. Histopathologic classifications can be useful as an additional predictive tool. The purpose of this study was to apply four grading systems (Multiparameter Grading System, Malignancy Grading of the Deep Invasive Margins, World Health Organization grading system, and Histologic Risk Assessment) to oral squamous cell carncinomas and evaluate each system based on clinicopathologic parameters and patient survival. METHODS The files of 53 patients diagnosed with primary oral squamous cell carcinoma at the Brazilian National Cancer Institute were evaluated. All hematoxylin and eosin-stained slides were reviewed to confirm the original diagnosis and to determine histopathologic grading. Clinicopathologic information was obtained from medical records and tumor registries. Statistical analysis was performed using Fisher's exact test or the chi-square test, the Kaplan-Meier method, and the log-rank test. RESULTS The Multiparameter Grading System was statistically associated with pathologic staging (P = 0.02) and lymph node involvement (P = 0.0009). Differences in overall 5-year survival were significant for Histologic Risk Assessment (P = 0.015), pathologic staging (P = 0.001), lymph node status (P < 0.0001), and recurrence (P = 0.0001). Differences in cancer-specific 5-year survival were significant for Histologic Risk Assessment (P = 0.029), pathologic staging (P = 0.002), lymph node involvement (P < 0.0001), and recurrence (P < 0.0001). Poorly differentiated tumors were associated with the worst disease-free survival (P = 0.031) and recurrence (P = 0.043). CONCLUSION Of the grading systems evaluated, Histologic Risk Assessment demonstrated the best results for survival prediction in oral squamous cell carcinoma.
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