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Gómez Pérez LJ, Cardullo S, Zaffaina GC, Cuppone D, Chindamo S, Zattin A, Cellini N, Terraneo A, Gallimberti L. Prognostic factors of a multidisciplinary rtms-based treatment for cocaine use disorder: A large cohort study. JOURNAL OF SUBSTANCE USE AND ADDICTION TREATMENT 2025; 174:209706. [PMID: 40286859 DOI: 10.1016/j.josat.2025.209706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 02/14/2025] [Accepted: 04/23/2025] [Indexed: 04/29/2025]
Abstract
INTRODUCTION This study investigated psychological and clinical factors influencing treatment outcomes for Cocaine Use Disorder (CocUD) patients undergoing a multidisciplinary approach, including repetitive Transcranial Magnetic Stimulation (rTMS), addiction counseling, pharmacological treatment, and psychotherapeutic support. Multidisciplinary treatments appear to be more effective than stand-alone programs in addiction recovery. METHODS This is a retrospective observational study of 1011 patients meeting DSM-5 criteria for CocUD undergoing a multidisciplinary treatment rTMS-based. The primary outcomes were (1) the time to the first lapse, (2) the time to dropout from the program, and (3) the monthly cocaine use pattern for up to one year since clinical admission. The secondary indices were the variations in the withdrawal symptoms. The influence of various factors on the time to first lapse and treatment dropout was analyzed using multivariate Cox proportional hazard models, which helps understand how different factors influence the time until an event, such as relapse or dropout, occurs. Concerning cocaine use patterns and secondary outcomes, linear mixed models were applied. RESULTS Protective factors comprise personal initiative in seeking treatment, starting with inpatient care, a higher number of high frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC), and referral to psychotherapy. In contrast, risk factors were psychiatric comorbidity (e.g., personality disorder, other addictions, alcohol use disorder), craving intensity, last use before treatment admission, and number of pharmacological prescriptions. Moreover, an increase in the number of high frequency rTMS over the left DLPFC sessions was a significant predictor of the reduction of severity on self-reported measures of psychiatric symptoms. CONCLUSIONS Personal initiative in seeking treatment and psychotherapy emerged as protective factors along with high frequency rTMS over the left DLPFC in determining positive outcomes, including a reduction in the severity of co-occurring psychiatric CocUD symptoms, underlining the benefit of a multidimensional approach to treating CocUD.
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Affiliation(s)
| | - Stefano Cardullo
- Novella Fronda Foundation, Padua, Italy; Mental Health Centre, Department of Mental Health - AULSS 6 Euganea, Padua, Italy
| | | | | | | | | | - Nicola Cellini
- Department of General Psychology, University of Padova, Padua, Italy
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Liao Y, Yang P, Yang C, Zhuang K, Fahira A, Wang J, Liu Z, Yan L, Huang Z. Clinical signature and associated immune metabolism of NLRP1 in pan-cancer. J Cell Mol Med 2024; 28:e70100. [PMID: 39318060 PMCID: PMC11422451 DOI: 10.1111/jcmm.70100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 06/07/2024] [Accepted: 09/09/2024] [Indexed: 09/26/2024] Open
Abstract
Inflammations have been linked to tumours, suggesting a potential association between NLRP1 and cancer. Nevertheless, a systematic assessment of NLRP1's role across various cancer types currently absent. A comprehensive bioinformatic analysis was conducted to determine whether NLRP1 exhibits prognostic relevance linked to immune metabolism across various cancers. The study leveraged data from the TCGA and GTEx databases to explore the clinical significance, metabolic features, and immunological characteristics of NLRP1, employing various tools such as R, GEPIA, STRING and TISIDB. NLRP1 exhibited differential expression patterns across various cancers, with elevated expression correlating with a more favourable prognosis in lung adenocarcinoma (LUAD) and pancreatic adenocarcinoma (PAAD). Downregulation of NLRP1 reduced tumour metabolic activity in LUAD. Moreover, the mutational signature of NLRP1 was linked to a favourable prognosis. Interestingly, high NLRP1 expression inversely correlated with tumour stemness while positively correlating with tumour immune infiltration in various cancers including LUAD and PAAD. Through extensive big data analysis, we delved into the role of NLRP1 across various tumour types, constructing a comprehensive role map of its involvement in pan-cancer scenarios. Our findings highlight the potential of NLRP1 as a promising therapeutic target specifically in LUAD and PAAD.
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Affiliation(s)
- Yong Liao
- Key Laboratory of Computer-Aided Drug Design of Dongguan City, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, China
| | - Pinglian Yang
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China
| | - Cui Yang
- Key Laboratory of Computer-Aided Drug Design of Dongguan City, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, China
| | - Kai Zhuang
- Key Laboratory of Computer-Aided Drug Design of Dongguan City, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China
| | - Aamir Fahira
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, China
| | - Jiaojiao Wang
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, China
| | - Zhiping Liu
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China
| | - Lin Yan
- Key Laboratory of Computer-Aided Drug Design of Dongguan City, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China
| | - Zunnan Huang
- Key Laboratory of Computer-Aided Drug Design of Dongguan City, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, China
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Wu J, Wang Y, Vlasschaert C, Lali R, Feiner J, Gaheer P, Yang S, Perrot N, Chong M, Paré G, Lanktree MB. Kidney Volume and Risk of Incident Kidney Outcomes. J Am Soc Nephrol 2024; 35:00001751-990000000-00349. [PMID: 38857205 PMCID: PMC11387033 DOI: 10.1681/asn.0000000000000419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 06/04/2024] [Indexed: 06/12/2024] Open
Abstract
BACKGROUND Low total kidney volume (TKV) is a risk factor for chronic kidney disease (CKD). However, evaluations of nonlinear relationships, incident events, causal inference, and prognostic utility beyond traditional biomarkers are lacking. METHODS TKV, height-adjusted TKV, and body surface area-adjusted TKV (BSA-TKV) of 34,595 White British ancestry participants were derived from the UK Biobank. Association with incident CKD, acute kidney injury (AKI), and cardiovascular events were assessed with Cox proportional hazard models. Prognostic thresholds for CKD risk stratification were identified using a modified Mazumdar method with bootstrap resampling. Two-sample Mendelian randomization was performed to assess the bidirectional association of genetically predicted TKV with kidney and cardiovascular traits. RESULTS Adjusted for eGFR and albuminuria, a lower TKV of 10 mL was associated with a 6% higher risk of incident CKD (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03 to 1.08, P = 5.8 x 10-6) in contrast to no association with incident AKI (HR 1.00, 95% CI 0.98 to 1.02, P = 0.66). Comparison of nested models demonstrated improved accuracy over the CKD Prognosis Consortium Incident CKD Risk Score with the addition of BSA-TKV or prognostic thresholds at 119 (10th percentile) and 145 mL/m2 (50th percentile). In Mendelian randomization, a lower genetically predicted TKV by 10 mL was associated with 10% higher CKD risk (odds ratio [OR] 1.10, 95% CI 1.06 to 1.14, P = 1.3 x 10-7). Reciprocally, an elevated risk of genetically predicted CKD by 2-fold was associated with a lower TKV by 7.88 mL (95% CI -9.81 to -5.95, P = 1.2 x 10-15). There were no significant observational or Mendelian randomization associations of TKV with cardiovascular complications. CONCLUSIONS Kidney volume was associated with incident CKD independent of traditional risk factors including baseline eGFR and albuminuria. Mendelian randomization demonstrated a bidirectional relationship between kidney volume and CKD.
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Affiliation(s)
- Jianhan Wu
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | - Yifan Wang
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | | | - Ricky Lali
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | - James Feiner
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | - Pukhraj Gaheer
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | - Serena Yang
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | - Nicolas Perrot
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
| | - Michael Chong
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Guillaume Paré
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Matthew B Lanktree
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
- Division of Nephrology, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada
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Luvián-Morales J, Delgadillo-González M, Castro-Eguiluz D, Oñate-Ocaña LF, Cetina-Pérez L. Quality of life but not cachexia definitions are associated with overall survival in women with cervical cancer: a STROBE-compliant cohort study. Jpn J Clin Oncol 2024; 54:416-423. [PMID: 38146122 DOI: 10.1093/jjco/hyad182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/08/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Cancer-related cachexia (CRC) has a profound impact on health-related quality of life (HRQL), and both were reported to be associated with overall survival (OS). We hypothesize that HRQL and CRC are associated with OS. This study analyzed the impact of CRC on HRQL and its prognostic value in women with cervical cancer (CC). METHODS A cohort study including consecutive women with CC treated from October 2020 to October 2021 in a cancer center. Cox's model defined the associations of immune, biochemical and nutritional parameters, clinical cachexia classifications and HRQL with OS. RESULTS Two hundred forty-four consecutive women with CC were included. Cachexia classifications and several scales of the QLQ-C30 were associated with OS by bivariate but not by multivariate analysis. QLQ-CX24 scales were not associated with OS. The prognostic nutritional index (PNI) (hazard ratio (HR) 0.828; 95% confidence interval (CI) 0.766-0.896), Food aversion (HR 0.95; 95% CI 0.924-0.976), Eating difficulties (HR 1.041; 95% CI 1.013-1.071), Loss of control (HR 4.131; 95% CI 1.317-12.963), Forced self to eat (1.024; 95% CI 1.004-1.044) and Indigestion (HR 0.348; 95% CI 0.131-0.928) scales of the QLQ-CAX24 were independently associated with OS by multivariate analysis (p = 1.9×10-11). CONCLUSION This model permitted a clear stratification of prognostic subgroups. The PNI and several QLQ-CAX24 scales were associated with OS in women with CC. CRC, defined by several cachexia classifications, was not an independent prognostic factor. These findings require confirmation because of their possible diagnostic, therapeutic and prognostic implications.The prognostic nutritional index and several QLQ-CAX24 scales were associated with overall survival in women with cervical cancer. Cancer-related cachexia, defined by several cachexia classifications, was not an independent prognostic factor, neither The International Federation of Gynecology and Obstetrics (FIGO) stage classifications.
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Affiliation(s)
- Julissa Luvián-Morales
- Modelo Integral para la Atención del Cáncer Cervicouterino Localmente Avanzado y Avanzado (MICAELA), Instituto Nacional de Cancerología (INCan), Mexico City
| | - Merari Delgadillo-González
- Modelo Integral para la Atención del Cáncer Cervicouterino Localmente Avanzado y Avanzado (MICAELA), Instituto Nacional de Cancerología (INCan), Mexico City
| | - Denisse Castro-Eguiluz
- Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City
- Investigador por México, CONAHCyT, Mexico City, Mexico
| | - Luis F Oñate-Ocaña
- Modelo Integral para la Atención del Cáncer Cervicouterino Localmente Avanzado y Avanzado (MICAELA), Instituto Nacional de Cancerología (INCan), Mexico City
- Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City
| | - Lucely Cetina-Pérez
- Modelo Integral para la Atención del Cáncer Cervicouterino Localmente Avanzado y Avanzado (MICAELA), Instituto Nacional de Cancerología (INCan), Mexico City
- Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City
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Huang M, Liu B, Li X, Li N, Yang X, Wang Y, Zhang S, Lu F, Li S, Yan S, Wu N. Beneficial implications of adjuvant chemotherapy for stage IB lung adenocarcinoma exhibiting elevated SUVmax in FDG-PET/CT: a retrospective study from a single center. Front Oncol 2024; 14:1367200. [PMID: 38529383 PMCID: PMC10961360 DOI: 10.3389/fonc.2024.1367200] [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: 01/08/2024] [Accepted: 02/26/2024] [Indexed: 03/27/2024] Open
Abstract
Background Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.
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Affiliation(s)
- Miao Huang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Bing Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiang Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Nan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xin Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yaqi Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Shanyuan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Fangliang Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Shaolei Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Shi Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Nan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
- State Key Laboratory of Molecular Oncology, Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
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Shakhgeldyan KI, Kuksin NS, Domzhalov IG, Rublev VY, Geltser BI. Interpretable machine learning for in-hospital mortality risk prediction in patients with ST-elevation myocardial infarction after percutaneous coronary interventions. Comput Biol Med 2024; 170:107953. [PMID: 38224666 DOI: 10.1016/j.compbiomed.2024.107953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/22/2023] [Accepted: 01/01/2024] [Indexed: 01/17/2024]
Abstract
BACKGROUND AND OBJECTIVE Despite the constant improvement of coronary heart disease (CHD) diagnostics and treatment methods it remains one of the main causes of death in most countries around the world. And myocardial infarction with ST segment elevation on the electrocardiogram (STEMI) still is one of the most dangerous clinical variants of CHD. This study aims to develop an explainable machine learning model for in-hospital mortality (IHM) risk prediction in STEMI patients after myocardial revascularization by percutaneous coronary intervention (PCI). METHODS A single-center observational retrospective study was conducted, enrolling 4677 electronic medical records of patients with STEMI after PCI, which were analyzed using statistical analysis and machine learning methods. A pool of potential IHM predictors was identified, and prognostic models were developed and validated based on multivariate logistic regression, random forest, and stochastic gradient boosting methods at two stages of hospital treatment: during the initial physicians examination in the emergency department and immediately after PCI surgery. To explain the IHM prognosis, threshold values of IHM risk factors were determined using 3 grid search methods for optimal cut-off points, calculating centroids and SHapley Additive exPlanations (SHAP). RESULTS IHM prognostic models were developed using clinical and functional status data of STEMI patients during two stages of hospital treatment. The IHM prediction accuracy according to the first scenario was AUC = 0.85, and according to the second - AUC = 0.9. Predictors identified and validated in the models were converted into risk factors. Models whose parameters were risk factors demonstrated high forecast accuracy (AUC = 0.87), with the best model formed using the SHAP method. CONCLUSIONS For the forecast result interpretation risk factors obtained by categorizing continuous variables can be used by assessing the impact of the latter on the end point using the SHAP method.
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Affiliation(s)
- Karina Iosephovna Shakhgeldyan
- Far Eastern Federal University, School of Medicine and Life Science, 10 Ajax Bay, Russky Island, 690922, Vladivostok, Russia; Vladivostok State University, Institute of Information Technology, Gogolya St. 41, 690014, Vladivostok, Russia.
| | - Nikita Sergeevich Kuksin
- Far Eastern Federal University, Institute of Mathematics and Computer Technology, 10 Ajax Bay, Russky Island, 690922, Vladivostok, Russia.
| | - Igor Gennadievich Domzhalov
- Far Eastern Federal University, School of Medicine and Life Science, 10 Ajax Bay, Russky Island, 690922, Vladivostok, Russia.
| | - Vladislav Yurievich Rublev
- Far Eastern Federal University, School of Medicine and Life Science, 10 Ajax Bay, Russky Island, 690922, Vladivostok, Russia; Vladivostok State University, Institute of Information Technology, Gogolya St. 41, 690014, Vladivostok, Russia.
| | - Boris Izrajlevich Geltser
- Far Eastern Federal University, School of Medicine and Life Science, 10 Ajax Bay, Russky Island, 690922, Vladivostok, Russia.
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Torasawa M, Horinouchi H, Nomura S, Igawa S, Asai M, Ishii H, Wakui H, Ushio R, Asao T, Namba Y, Koyama R, Hayakawa D, Katayama I, Matsuda H, Sasaki S, Takahashi K, Hosomi Y, Naoki K, Ohe Y. Reconsidering the Cutoff Value for Sensitive and Refractory Relapses in Extensive-Stage SCLC in the Era of Immunotherapy. J Thorac Oncol 2024; 19:325-336. [PMID: 37748690 DOI: 10.1016/j.jtho.2023.09.1446] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/28/2023] [Accepted: 09/20/2023] [Indexed: 09/27/2023]
Abstract
INTRODUCTION Traditionally, relapsed SCLC has been classified as "sensitive" or "refractory" on the basis of cutoff values (60 or 90 d) for the duration between the last chemotherapy and disease progression. Nevertheless, these cutoff values are not derived from rigorous analytical methods, and their applicability to contemporary treatments remains uncertain. METHODS We conducted a retrospective multicenter study on patients with extensive-stage SCLC who underwent second-line therapy after platinum-doublet chemotherapy with or without immune checkpoint inhibitor (ICI) resistance before (pre-ICI cohort) and after (post-ICI cohort) approval of combination immunotherapy. We selected the optimal platinum-free interval cutoff value with the lowest two-sided p value in the multivariable Cox regression model for second-line overall survival. The internal validity of the chosen cutoff value was assessed using twofold cross-validation. RESULTS There were 235 and 98 patients in the pre-ICI and post-ICI cohorts, respectively. In the pre-ICI cohort, the optimal cutoff was 59 days (p = 0.0001); the hazard ratio calculated using twofold cross-validation was 1.31 (95% confidence interval: 0.95-1.82]). In the post-ICI cohort, although the 60- and 90-day cutoff values could predict prognosis (60 d; p = 0.002, 90 d; p = 0.005), the optimal cutoff value was 75 days (p = 0.0002), which resulted in a median second-line overall survival of 15.9 and 5.0 months for patients with sensitive and refractory relapse, respectively (hazard ratio = 2.77, 95% confidence interval: 1.56-4.93). CONCLUSIONS We clarified the previously ambiguous cutoff values for classifying relapsed SCLC and revealed that the 75-day cutoff most accurately predicts subsequent prognosis than the traditional cutoffs in the post-ICI era.
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Affiliation(s)
- Masahiro Torasawa
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hidehito Horinouchi
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
| | - Shogo Nomura
- Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Satoshi Igawa
- Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Maiko Asai
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Hidenobu Ishii
- Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hiroshi Wakui
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Ryota Ushio
- Department of Respiratory Medicine, Kanagawa Cancer Center, Kanagawa, Japan
| | - Tetsuhiko Asao
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yukiko Namba
- Department of Respiratory Medicine, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Ryo Koyama
- Department of Respiratory Medicine, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Daisuke Hayakawa
- Department of Respiratory Medicine, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Isana Katayama
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Hironari Matsuda
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Shinichi Sasaki
- Department of Respiratory Medicine, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Kazuhisa Takahashi
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yukio Hosomi
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Katsuhiko Naoki
- Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Yuichiro Ohe
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
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Huang BT, Lin PX, Wang Y, Luo LM. Developing a Prediction Model for Radiation Pneumonitis in Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy Combined With Clinical, Dosimetric Factors, and Laboratory Biomarkers. Clin Lung Cancer 2023; 24:e323-e331.e2. [PMID: 37648569 DOI: 10.1016/j.cllc.2023.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/31/2023] [Accepted: 08/04/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND The study aims to identify the risk factors and develop a model for predicting grade ≥2 radiation pneumonitis (RP) for lung cancer patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS Clinical data, dosimetric data, and laboratory biomarkers from 186 patients treated with lung SBRT were collected. Univariate and multivariate logistic regression were performed to determine the predictive factors for grade ≥2 RP. Three models were developed by using the clinical, dosimetric, and combined factors, respectively. RESULTS With a median follow-up of 36 months, grade ≥2 RP was recorded in 13.4% of patients. On univariate logistic regression analysis, clinical factors of age and lung volume, dosimetric factors of treatment durations, fractional dose and V10, and laboratory biomarkers of neutrophil, PLT, PLR, and Hb levels were significantly associated with grade ≥2 RP. However, on multivariate analysis, only age, lung volume, fractional dose, V10, and Hb levels were independent factors. AUC values for the clinical, dosimetric, and combined models were 0.730 (95% CI, 0.660-0.793), 0.711 (95% CI, 0.641-0.775) and 0.830 (95% CI, 0.768-0.881), respectively. The combined model provided superior discriminative ability than the clinical and dosimetric models (P < .05). CONCLUSION Age, lung volume, fractional dose, V10, and Hb levels were demonstrated to be significant factors associated with grade ≥2 RP for lung cancer patients after SBRT. A novel model combining clinical, dosimetric factors, and laboratory biomarkers improved predictive performance compared with the clinical and dosimetric model alone.
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Affiliation(s)
- Bao-Tian Huang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China.
| | - Pei-Xian Lin
- Department of Nosocomial Infection Management, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Ying Wang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Li-Mei Luo
- Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
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9
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Duceppe E, Borges FK, Tiboni M, Pearse R, Chan MTV, Srinathan S, Kavsak PA, Garg AX, Sessler DI, Sapsford R, Heels-Ansdell D, Pettit S, Vasquez J, Mueller C, Walsh M, Szczeklik W, Rodseth R, Lalu M, Thabane L, Guyatt G, Devereaux PJ. High-Sensitivity Cardiac Troponin I Thresholds to Identify Myocardial Injury After Noncardiac Surgery: A Cohort Study. Can J Cardiol 2023; 39:311-318. [PMID: 36682485 DOI: 10.1016/j.cjca.2023.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Myocardial injury after noncardiac surgery (MINS) is common and associated with short- and long-term major cardiovascular events. Diagnostic criteria for MINS using Abbott high-sensitivity cardiac troponin I (hs-cTnI) are unknown. METHODS We performed a prospective cohort study of adults who had in-patient noncardiac surgery and measured hs-cTnI (Abbott Laboratories) on postoperative serum samples collected up to postoperative day 3. The objective was to determine prognostically important hs-cTnI thresholds associated with major cardiac events and death at 30 days after noncardiac surgery. Using Cox proportional iterative analyses, we determined peak postoperative hs-cTnI thresholds associated with the occurrence of the 30-day composite of major cardiac events (ie, nonfatal myocardial infarction after 3 postoperative days, cardiac arrest, and congestive heart failure) and death. RESULTS Of 3953 included patients, 66 (1.7%) experienced the primary outcome at 30 days. Peak hs-cTnI values and associated incidence of major cardiac events and death were as follows: < 60 ng/L: 1.0% (95% CI 0.7-1.3); 60 to < 700 ng/L: 8.6% (5.6-13.0); and ≥ 700 ng/L: 27.3% (16.4-41.9). Compared with peak hs-cTnI < 60 ng/L, adjusted hazard ratios were 7.54 (95% CI% 4.27-13.32) for hs-cTnI values of 60 to < 700 ng/L and 26.87 (13.27-54.41) for values ≥ 700 ng/L. CONCLUSIONS Hs-cTnI elevation within the first 3 days after noncardiac surgery independently predicts major cardiac events and death at 30 days. A postoperative hs-cTnI ≥ 60 ng/L was associated with a > 7-fold increase in the risk of subsequent major cardiac events and mortality at 30 days.
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Affiliation(s)
- Emmanuelle Duceppe
- Department of Medicine, Centre Hospitalier de l'Universite de Montréal, Montréal, Québec, Canada; Population Health Research Institute, Hamilton, Ontario, Canada.
| | - Flavia K Borges
- Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Maria Tiboni
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Rupert Pearse
- Translational Medicine and Therapeutics William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | | | - Sadeesh Srinathan
- Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Peter A Kavsak
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Amit X Garg
- Department of Medicine, Western University, London, Ontario, Canada
| | - Daniel I Sessler
- Department of Outcome Research, Cleveland Clinic, Cleveland, Ohio, United States
| | - Robert Sapsford
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Diane Heels-Ansdell
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Shirley Pettit
- Population Health Research Institute, Hamilton, Ontario, Canada
| | - Javiera Vasquez
- Anaesthesiology Department, Clinica Santa Maria, Santiago. Universidad de los Andes, Santiago, Chile
| | - Christian Mueller
- Department of Cardiology, University Hospital Basel, Basel, Switzerland
| | - Micheal Walsh
- Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Wojciech Szczeklik
- Center for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Reitze Rodseth
- Department of Anaesthesia, University of KwaZulu-Natal, Durban, South Africa
| | - Manoj Lalu
- Department of Anaesthesiology and Pain Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Gordon Guyatt
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - P J Devereaux
- Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
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10
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Borges FK, Duceppe E, Heels-Ansdell D, Patel A, Sessler DI, Tandon V, Chan M, Pearse R, Srinathan S, Garg AX, Sapsford RJ, Ofori SN, Marcucci M, Kavsak PA, Pettit S, Spence J, Belley-Cote E, McGillion M, Whitlock R, Lamy A, Conen D, Thomas S, Mueller C, Jaffe AS, Devereaux PJ. High-sensitivity Troponin I Predicts Major Cardiovascular Events after Non-Cardiac Surgery: A Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Substudy. Clin Chem 2023; 69:492-499. [PMID: 36762424 DOI: 10.1093/clinchem/hvad005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 01/03/2023] [Indexed: 02/11/2023]
Abstract
BACKGROUND Myocardial injury after non-cardiac surgery (MINS), based on measurement of troponin T, is associated with perioperative major adverse cardiovascular events (MACE). We therefore determined the high-sensitivity troponin I (hsTnI) thresholds associated with 30 day MACE after non-cardiac surgery. METHODS We performed a nested biobank cohort study of 4553 patients from the Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Study. We measured hsTnI (ADVIA Centaur® hsTnI assay) on postoperative days 1 to 3 in patients ≥45 years undergoing non-cardiac surgery. An iterative Cox proportional hazard model determined peak postoperative hsTnI thresholds independently associated with MACE (i.e., death, myocardial infarction occurring on postoperative day 4 or after, non-fatal cardiac arrest, or congestive heart failure) within 30 days after surgery. RESULTS MACE occurred in 89/4545 (2.0%) patients. Peak hsTnI values of <75 ng/L, 75 ng/L to <1000 ng/L, and ≥1000 ng/L were associated with 1.2% (95% CI, 0.9-1.6), 7.1% (95% CI, 4.8-10.5), and 25.9% (95% CI, 16.3-38.4) MACE, respectively. Compared to peak hsTnI <75 ng/L, values 75 ng/L to <1000 ng/L and ≥1000 ng/L were associated with adjusted hazard ratios (aHR) of 4.53 (95% CI, 2.75-7.48) and 16.17 (95% CI, 8.70-30.07), respectively. MACE was observed in 9% of patients with peak hsTnI ≥75 ng/L vs 1% in patients with peak hsTnI <75 ng/L (aHR 5.76; 95% CI, 3.64-9.11). A peak hsTnI ≥75 ng/L was associated with MACE in the presence (aHR 9.35; 95% CI, 5.28-16.55) or absence (aHR 3.99; 95% CI, 2.19-7.25) of ischemic features of myocardial injury. CONCLUSION A peak postoperative hsTnI ≥75 ng/L was associated with >5-fold increase in the risk of 30 days MACE compared to levels <75 ng/L. This threshold could be used for MINS diagnosis when the ADVIA Centaur hsTnI assay is used. Clinicaltrials.gov Registration Number: NCT00512109.
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Affiliation(s)
- Flavia K Borges
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Medicine, McMaster University, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Emmanuelle Duceppe
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Medicine, University of Montreal, Montreal, Canada
| | - Diane Heels-Ansdell
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Ameen Patel
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Daniel I Sessler
- Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio, United States
| | - Vikas Tandon
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Matthew Chan
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Rupert Pearse
- Department of Critical Care, Queen Mary University of London and Barts Health NHS Trust, London, United Kingdom
| | | | - Amit X Garg
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.,Division of Nephrology, London Health Sciences Centre Research Institute, London, Canada
| | - Robert J Sapsford
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Sandra N Ofori
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Maura Marcucci
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Medicine, McMaster University, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Peter A Kavsak
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
| | - Shirley Pettit
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada
| | - Jessica Spence
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Anesthesia, McMaster University, Hamilton, Canada
| | - Emilie Belley-Cote
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Medicine, McMaster University, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Michael McGillion
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,School of Nursing, McMaster University, Hamilton, Canada
| | - Richard Whitlock
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Surgery, McMaster University, Hamilton, Canada
| | - Andre Lamy
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Surgery, McMaster University, Hamilton, Canada
| | - David Conen
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Medicine, McMaster University, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Sabu Thomas
- Division of Cardiology, University of Rochester School of Medicine, Rochester, New York, United States
| | - Christian Mueller
- Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Allan S Jaffe
- Department of Cardiovascular Diseases, and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, New York, United States
| | - P J Devereaux
- Department of Perioperative Medicine, Population Health Research Institute, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
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11
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Shah SH, Xiao L, Chen YF, Moss HE, Rubin DS, Roth S. Perioperative Ischemic Optic Neuropathy after Cardiac Surgery: Development and Validation of a Preoperative Risk Prediction Model. J Cardiothorac Vasc Anesth 2022; 36:4266-4272. [PMID: 36114093 PMCID: PMC10874298 DOI: 10.1053/j.jvca.2022.08.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 07/31/2022] [Accepted: 08/08/2022] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Previous studies identified risk factors for ischemic optic neuropathy (ION) after cardiac surgery; however, there is no easy-to-use risk calculator for the physician to identify high-risk patients for ION before cardiac surgery. The authors sought to develop and validate a simple-to-use predictive model and calculator to assist with preoperative identification of risk and informed consent for this rare but serious complication. DESIGN Retrospective case-control study. SETTING Hospital discharge records. PATIENTS A total of 5,561,177 discharges in the National Inpatient Sample >18 years of age, with procedure codes for coronary artery bypass grafting, heart valve repair/replacement, or left ventricular assist device insertion. INTERVENTIONS All patients had undergone cardiac surgery. MEASUREMENTS AND MAIN RESULTS Known preoperative risk factors for ION after cardiac surgery were assessed to develop a risk score and prediction model. This model was validated internally using the split-sample method. There were 771 cases of ION among 5,561,177 patients in the National Inpatient Sample. The risk factors for ION used in the model were carotid artery stenosis, cataract, diabetic retinopathy, macular degeneration, glaucoma, male sex, and prior stroke; whereas uncomplicated diabetes decreased risk. With the internal validation, the predictive model had an area under the receiver operating characteristic curve of 0.66. A risk score cutoff ≥3 had 98.4% specificity. CONCLUSIONS This predictive model, based on previously identified preoperative factors, predicted risk of perioperative ION with a fair area under the receiver operating characteristic curve. This predictive model could enable screening to provide a more accurate risk assessment for ION, and consent process for cardiac surgery.
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Affiliation(s)
- Shikhar H Shah
- Department of Anesthesiology, Walter Reed National Military Medical Center, Washington, DC
| | - Lan Xiao
- Center for Community Engagement, Stanford University, Stanford, CA
| | - Yi-Fan Chen
- The Center for Clinical & Translational Sciences, University of Illinois at Chicago, Chicago, IL
| | - Heather E Moss
- Departments of Ophthalmology and Neurology and Neurologic Sciences, Stanford University, Stanford, CA
| | - Daniel S Rubin
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL
| | - Steven Roth
- Department of Anesthesiology, University of Illinois at Chicago College of Medicine, Chicago, IL; Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, Chicago, IL.
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12
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Lee SA, Yang HR, Im K, Choi EJ, Jeon JY, Han SH, Kim HW, Lee GH, Ryu HU. Comparisons of impulsivity among patients with different subtypes of epilepsy. Epilepsy Res 2022; 186:106997. [DOI: 10.1016/j.eplepsyres.2022.106997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 07/31/2022] [Accepted: 08/09/2022] [Indexed: 11/28/2022]
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13
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Perchermeier S, Tassani-Prell P. The Use of Corticosteroids for Cardiopulmonary Bypass in Adults. CURRENT ANESTHESIOLOGY REPORTS 2021. [DOI: 10.1007/s40140-021-00468-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Abstract
Purpose of Review
Cardiopulmonary bypass for on-pump cardiac surgery induces a systemic inflammation that may contribute to postoperative major complications. To reduce this inflammatory response in patients undergoing heart surgery, the perioperative use of anti-inflammatory corticosteroids has long been recommended to improve clinical outcomes. However, the efficacy and safety of steroids remain still unclear.
Recent Findings
We reviewed recent published literature, including the large clinical trials DECS and SIRS and the two meta-analysis by Dvirnik et al. (2018) and Ng et al. (2020), on mortality and major postoperative complications, such as myocardial complications, atrial fibrillation, stroke, pulmonary adverse events, length of ICU and hospital stay, renal failure, and infection.
Summary
The perioperative application of corticosteroids did not improve mortality rates beyond standard care or other secondary outcomes, such as myocardial infarction, stroke, renal failure, and infection. The observed increased risk of myocardial damage in patients receiving corticosteroids in the SIRS trial is mainly related to the author-defined CK-MB threshold as indicator for early myocardial injury. Interestingly, the use of steroids may have some beneficial effects on secondary outcomes: they significantly decreased the risk of respiratory failure and pneumonia and shortened the length of ICU and hospital stay, but the mechanism involved in pulmonary injury is multifactorial and it is difficult to evaluate this result. Patients receiving steroids did not have a decreased incidence of atrial fibrillation shown by the two large trials unlike some previous small sample size trials have demonstrated.
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14
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Boracchi P, Roccabianca P, Avallone G, Marano G. Kaplan-Meier Curves, Cox Model, and P-Values Are Not Enough for the Prognostic Evaluation of Tumor Markers: Statistical Suggestions for a More Comprehensive Approach. Vet Pathol 2021; 58:795-808. [PMID: 33977800 DOI: 10.1177/03009858211014174] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The assessment of prognostic markers is key to the improvement of therapeutic strategies for cancer patients. Some promising markers may fail to be applied in clinical practice, or some useless markers may be applied, because of misleading results ensuing from inadequate planning of the study and/or from an oversimplified statistical analysis. This commentary illustrates and discusses the main issues involved in planning an effective clinical study and the subsequent statistical analysis for the prognostic evaluation of a cancer marker. Another aim is to extend the most applied statistical models (ie, those using Kaplan-Meier and Cox) to enable the choice of the best-suited methods for study endpoints. Specifically, for tumor-centered endpoints like tumor recurrence, the issue of competing risks is highlighted. For markers measured on a continuous numerical scale, a loss of relevant prognostic information may occur by setting arbitrary cutoffs; thus, the methods to analyze the original scale are explained. Furthermore, because the P-value is not a sufficient criterion to assess the usefulness of a marker in clinical practice, measures for evaluating the ability of the marker to discriminate between "good" and "bad" prognoses are illustrated. Several tumor markers are considered both in human and veterinary medicine. Given the similarity between markers for human breast cancer and canine mammary cancer, an application of the statistical methods discussed within the article to a public dataset from human breast cancer patients is shown.
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Affiliation(s)
- Patrizia Boracchi
- Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", 9304Università degli Studi di Milano, Milan, Italy
| | - Paola Roccabianca
- Dipartimento di Medicina Veterinaria, 9304Università degli Studi di Milano, Milan, Italy
| | - Giancarlo Avallone
- Department of Veterinary Medical Sciences, 9296University of Bologna, Ozzano dell'Emilia, Italy
| | - Giuseppe Marano
- Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", 9304Università degli Studi di Milano, Milan, Italy
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15
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Zhao BC, Lei SH, Yang X, Zhang Y, Qiu SD, Liu WF, Li C, Liu KX. Assessment of prognostic value of intraoperative oliguria for postoperative acute kidney injury: a retrospective cohort study. Br J Anaesth 2021; 126:799-807. [PMID: 33342539 DOI: 10.1016/j.bja.2020.11.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 11/01/2020] [Accepted: 11/15/2020] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Oliguria is often viewed as a sign of renal hypoperfusion and an indicator for volume expansion during surgery. However, the prognostic association and the predictive utility of intraoperative oliguria for postoperative acute kidney injury (AKI) are unclear. METHODS We conducted a retrospective cohort study on patients undergoing major thoracic surgery in an academic hospital to assess the association of intraoperative oliguria with postoperative AKI and its predictive value. To contextualise our findings, we included our results in a meta-analysis of observational studies on the importance of oliguria during noncardiac surgery. RESULTS In our cohort study, 3862 patients were included; 205 (5.3%) developed AKI after surgery. Intraoperative urine output of 0.3 ml kg-1 h-1 was the optimal threshold for oliguria in multivariable analysis. Patients with oliguria had an increased risk of AKI (adjusted odds ratio: 2.60; 95% confidence interval: 1.24-5.05). However, intraoperative oliguria had a sensitivity of 5.9%, specificity of 98%, positive likelihood ratio of 2.74, and negative likelihood ratio of 0.96, suggesting poor predictive ability. Moreover, it did not improve upon the predictive performance of a multivariable model, based on discrimination and reclassification indices. Our findings were generally consistent with the results of a systematic review and meta-analysis, including six additional studies. CONCLUSIONS Intraoperative oliguria has moderate association with, but poor predictive ability for, postoperative AKI. It remains of clinical interest as a risk factor potentially modifiable to interventions.
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Affiliation(s)
- Bing-Cheng Zhao
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shao-Hui Lei
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao Yang
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ya Zhang
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shi-Da Qiu
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wei-Feng Liu
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Cai Li
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ke-Xuan Liu
- Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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16
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Tellier É, Simonnet B, Gil-Jardiné C, Lerouge-Bailhache M, Castelle B, Salmi R. Predicting drowning from sea and weather forecasts: development and validation of a model on surf beaches of southwestern France. Inj Prev 2021; 28:16-22. [PMID: 33692084 PMCID: PMC8788255 DOI: 10.1136/injuryprev-2020-044092] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/09/2021] [Accepted: 02/15/2021] [Indexed: 11/04/2022]
Abstract
Objective To predict the coast-wide risk of drowning along the surf beaches of Gironde, southwestern France. Methods Data on rescues and drownings were collected from the Medical Emergency Center of Gironde (SAMU 33). Seasonality, holidays, weekends, weather and metocean conditions were considered potentially predictive. Logistic regression models were fitted with data from 2011 to 2013 and used to predict 2015–2017 events employing weather and ocean forecasts. Results Air temperature, wave parameters, seasonality and holidays were associated with drownings. Prospective validation was performed on 617 days, covering 232 events (rescues and drownings) reported on 104 different days. The area under the curve (AUC) of the daily risk prediction model (combined with 3-day forecasts) was 0.82 (95% CI 0.79 to 0.86). The AUC of the 3-hour step model was 0.85 (95% CI 0.81 to 0.88). Conclusions Drowning events along the Gironde surf coast can be anticipated up to 3 days in advance. Preventative messages and rescue preparations could be increased as the forecast risk increased, especially during the off-peak season, when the number of available rescuers is low.
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Affiliation(s)
- Éric Tellier
- Pôle Urgences adultes SAMU-SMUR, CHU Bordeaux GH Pellegrin, Bordeaux, France .,Bordeaux Population Health, Université de Bordeaux Collège Sciences de la Santé, Bordeaux, France
| | - Bruno Simonnet
- Pôle Urgences adultes SAMU-SMUR, CHU Bordeaux GH Pellegrin, Bordeaux, France
| | - Cédric Gil-Jardiné
- Pôle Urgences adultes SAMU-SMUR, CHU Bordeaux GH Pellegrin, Bordeaux, France.,Bordeaux Population Health, Université de Bordeaux Collège Sciences de la Santé, Bordeaux, France
| | - Marion Lerouge-Bailhache
- Bordeaux Population Health, Université de Bordeaux Collège Sciences de la Santé, Bordeaux, France.,Pôle de Pédiatrie, CHU Bordeaux GH Pellegrin, Bordeaux, France
| | - Bruno Castelle
- UMR EPOC, CNRS, Pessac, France.,UMR EPOC, Université Bordeaux 1 UFR des Sciences de la Terre et de la Mer, Pessac, Aquitaine, France
| | - Rachid Salmi
- Bordeaux Population Health, Université de Bordeaux Collège Sciences de la Santé, Bordeaux, France.,Pôle de santé publique, Service d'information médicale, CHU Bordeaux GH Pellegrin, Bordeaux, France
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17
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Li W, Guo L, Xing Z, Fang X, Liang H, Zhang S, Shi L, Kuang C, Shi L, Zheng Y, Hu Y, Yang Q. Forty-three key gene expressions involved in the effect of indoleamine 2,3-dioxygenase 1 expression on cancer prognosis may be a potential indoleamine 2,3-dioxygenase 1 inhibitor biomarker. Clin Transl Med 2021; 11:e330. [PMID: 33634987 PMCID: PMC7888544 DOI: 10.1002/ctm2.330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 11/11/2022] Open
Affiliation(s)
- Weirui Li
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Leilei Guo
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Zikang Xing
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Xin Fang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Heng Liang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Shengnan Zhang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Lei Shi
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Chunxiang Kuang
- Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, China
| | - Leming Shi
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Yuanting Zheng
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Yueqing Hu
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, China
| | - Qing Yang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
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18
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Park J, Hyeon CW, Lee SH, Lee SM, Yeo J, Yang K, Min JJ, Lee JH, Yang JH, Song YB, Hahn JY, Choi SH, Choi JH, Gwon HC. Preoperative cardiac troponin below the 99th-percentile upper reference limit and 30-day mortality after noncardiac surgery. Sci Rep 2020; 10:17007. [PMID: 33046756 PMCID: PMC7550329 DOI: 10.1038/s41598-020-72853-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/18/2020] [Indexed: 11/08/2022] Open
Abstract
Preoperative high-sensitivity cardiac troponin (hs-cTn) above the 99th-percentile upper reference limit (URL) is associated with mortality after noncardiac surgery. This study aimed to evaluate whether preoperative hs-cTn concentrations above the lowest limit of detection (LOD) but below the 99th-percentile URL can predict mortality after noncardiac surgery.From January 2010 to April 2019, a total of 12,415 noncardiac surgical patients with preoperative hs-cTn I below the 99th-percentile URL were enrolled. The patients were divided into two groups according to preoperative hs-cTn I concentration: (1) [hs-cTn] below the LOD (6 ng/L), and (2) mildly elevated [hs-cTn] but below the 99th-percentile URL (40 ng/L). The primary outcome was 30-day mortality. Of the 12,415 patients enrolled, 7958 (64.1%) were in the LOD group whereas 4457 (35.9%) were in the mild elevation group. The incidence of 30-day mortality was significantly greater in the mild elevation group (2.1% vs. 4.0% hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.39-2.16; p < 0.001) in the multivariate analyses. The propensity score matched analyses also produced a similar result (2.6% vs. 4.2% HR 1.61; 95% CI 1.26-2.07; p < 0.001). The threshold at which the risk of mortality increased corresponded to a preoperative hs-cTn I ≥ 12 ng/L. Patients with preoperative hs-cTn I above the LOD and below the 99th-percentile URL had greater 30-day mortality after noncardiac surgery.
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Affiliation(s)
- Jungchan Park
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Cheol Won Hyeon
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
| | - Seung-Hwa Lee
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea.
| | - Sangmin Maria Lee
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Junghyun Yeo
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwangmo Yang
- Centers for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeong Jin Min
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Hwan Lee
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeong Hoon Yang
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
| | - Young Bin Song
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
| | - Joo-Yong Hahn
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
| | - Seung-Hyuk Choi
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
| | - Jin-Ho Choi
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyeon-Cheol Gwon
- Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Korea
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19
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Shakya R, Nguyen TH, Waterhouse N, Khanna R. Immune contexture analysis in immuno-oncology: applications and challenges of multiplex fluorescent immunohistochemistry. Clin Transl Immunology 2020; 9:e1183. [PMID: 33072322 PMCID: PMC7541822 DOI: 10.1002/cti2.1183] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/04/2020] [Accepted: 09/04/2020] [Indexed: 12/17/2022] Open
Abstract
The tumor microenvironment is an integral player in cancer initiation, tumor progression, response and resistance to anti-cancer therapy. Understanding the complex interactions of tumor immune architecture (referred to as 'immune contexture') has therefore become increasingly desirable to guide our approach to patient selection, clinical trial design, combination therapies, and patient management. Quantitative image analysis based on multiplexed fluorescence immunohistochemistry and deep learning technologies are rapidly developing to enable researchers to interrogate complex information from the tumor microenvironment and find predictive insights into treatment response. Herein, we discuss current developments in multiplexed fluorescence immunohistochemistry for immune contexture analysis, and their application in immuno-oncology, and discuss challenges to effectively use this technology in clinical settings. We also present a multiplexed image analysis workflow to analyse fluorescence multiplexed stained tumor sections using the Vectra Automated Digital Pathology System together with FCS express flow cytometry software. The benefit of this strategy is that the spectral unmixing accurately generates and analyses complex arrays of multiple biomarkers, which can be helpful for diagnosis, risk stratification, and guiding clinical management of oncology patients.
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Affiliation(s)
- Reshma Shakya
- QIMR Berghofer Centre for Immunotherapy and Vaccine Development, Tumour Immunology LaboratoryQIMR Berghofer Medical Research InstituteBrisbaneQLDAustralia
| | - Tam Hong Nguyen
- Flow Cytometry and Imaging FacilityQIMR Berghofer Medical Research InstituteBrisbaneQLDAustralia
| | - Nigel Waterhouse
- Flow Cytometry and Imaging FacilityQIMR Berghofer Medical Research InstituteBrisbaneQLDAustralia
| | - Rajiv Khanna
- QIMR Berghofer Centre for Immunotherapy and Vaccine Development, Tumour Immunology LaboratoryQIMR Berghofer Medical Research InstituteBrisbaneQLDAustralia
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20
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Labarca G, Dreyse J, Salas C, Letelier F, Schmidt A, Rivera F, Jorquera J. Clinical utility of oximetric parameters to identify a high‐risk phenotype of moderate‐severe Obstructive Sleep Apnea (OSA). CLINICAL RESPIRATORY JOURNAL 2020; 14:1166-1175. [DOI: 10.1111/crj.13256] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 07/31/2020] [Accepted: 08/06/2020] [Indexed: 12/19/2022]
Affiliation(s)
- Gonzalo Labarca
- Faculty of Medicine University of Concepcion Concepcion Chile
- Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy University of Concepcion Concepcion Chile
| | - Jorge Dreyse
- Centro de Enfermedades Respiratorias y grupo de estudio trastornos respiratorios del sueño (GETRS) Clínica Las Condes Santiago Chile
| | - Constanza Salas
- Centro de Enfermedades Respiratorias y grupo de estudio trastornos respiratorios del sueño (GETRS) Clínica Las Condes Santiago Chile
| | - Francisca Letelier
- Centro de Enfermedades Respiratorias y grupo de estudio trastornos respiratorios del sueño (GETRS) Clínica Las Condes Santiago Chile
| | - Alexia Schmidt
- Faculty of Medicine University of Concepcion Concepcion Chile
| | | | - Jorge Jorquera
- Centro de Enfermedades Respiratorias y grupo de estudio trastornos respiratorios del sueño (GETRS) Clínica Las Condes Santiago Chile
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21
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Spence J, Lamy A, Bosch J, Thabane L, Gagnon S, Power P, Browne A, Murkin J, Devereaux PJ. Feasibility of studying the association between intraoperative regional cerebral oxygen saturation and postoperative functional decline (ReFUNCTION): a pilot sub-study of NeuroVISION-Cardiac Surgery. Can J Anaesth 2020; 67:1497-1506. [PMID: 32767054 DOI: 10.1007/s12630-020-01777-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/15/2020] [Accepted: 05/18/2020] [Indexed: 12/01/2022] Open
Abstract
PURPOSE Function describes an individual's ability to perform everyday activities. In the context of cardiac surgery, functional changes quantify the effect of surgery on one's day-to-day life. Decreases in regional cerebral oxygen saturation (rScO2) measured using near-infrared spectroscopy (NIRS) has been associated with postoperative cognitive decline but its relationship with function has not been studied. We sought to determine the feasibility of conducting a large observational study examining the relationship between decreases in rScO2 during cardiac surgery and postoperative functional decline. METHODS We undertook a single-centre, pilot sub-study of the NeuroVISION-Cardiac Surgery pilot study, which included adults undergoing isolated coronary artery bypass grafting on cardiopulmonary bypass; all patients enrolled in NeuroVISION-Cardiac Surgery were included. Function was evaluated at baseline, 30 days, and three months using the Standardized Assessment of Global activities in the Elderly (SAGE) scale. Blinded NIRS monitors were affixed for the duration of surgery. Our feasibility outcomes were to recruit one patient per week, obtain complete NIRS data in ≥ 90%, obtain SAGE at all time-points in ≥ 90%, and determine the time required for NIRS data to be transcribed into case report forms. RESULTS 49/50 patients enrolled in NeuroVISION-Cardiac Surgery were recruited over 48 weeks (1.02 patients/week). Of the 49 included patients, 49 (100%) had complete NIRS data and 44 (90%) had complete SAGE data. The time required for NIRS data collection was a mean (standard deviation) of 5.5 (1.8) min per patient. CONCLUSION This pilot study shows the feasibility of conducting a large observational study examining the relationship between decreases in cerebral saturation during cardiac surgery and postoperative functional decline. TRIAL REGISTRATION www.clinicaltrials.gov (NCT04241289); registered 27 January 2020.
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Affiliation(s)
- Jessica Spence
- Departments of Anesthesia and Critical Care and Health Research Methods, Evaluation, and Impact, McMaster University, Hamilton, Canada. .,Population Health Research Institute, Hamilton, ON, Canada.
| | - Andre Lamy
- Population Health Research Institute, Hamilton, ON, Canada.,Departments of Surgery (Cardiac Surgery) and Health Research Methods, Evaluation, and Impact, McMaster University, Hamilton, Canada
| | - Jackie Bosch
- Population Health Research Institute, Hamilton, ON, Canada.,School of Rehabilitation Science, McMaster University, Hamilton, Canada
| | - Lehana Thabane
- Population Health Research Institute, Hamilton, ON, Canada.,Department of Health Research Methods, Evaluation, and Impact, McMaster University, Hamilton, Canada
| | | | - Patricia Power
- Population Health Research Institute, Hamilton, ON, Canada
| | - Austin Browne
- Population Health Research Institute, Hamilton, ON, Canada
| | - John Murkin
- Department of Anesthesiology and Perioperative Medicine, University of Western Ontario, London, ON, Canada
| | - P J Devereaux
- Population Health Research Institute, Hamilton, ON, Canada.,Departments of Medicine and Health Research Methods, Evaluation, and Impact, McMaster University, Hamilton, Canada
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22
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Kano K, Sakamaki K, Oue N, Kimura Y, Hashimoto I, Hara K, Maezawa Y, Aoyama T, Fujikawa H, Hiroshima Y, Yamada T, Tamagawa H, Yamamoto N, Ogata T, Cho H, Ito H, Shiozawa M, Yukawa N, Yoshikawa T, Morinaga S, Rino Y, Yasui W, Masuda M, Miyagi Y, Oshima T. Impact of the ESM-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy. In Vivo 2020; 34:461-467. [PMID: 31882514 DOI: 10.21873/invivo.11796] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 11/04/2019] [Accepted: 11/06/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND/AIM Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. PATIENTS AND METHODS The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. RESULTS A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). CONCLUSION ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.
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Affiliation(s)
- Kazuki Kano
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Kentaro Sakamaki
- Department of Biostatistics and Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naohide Oue
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Science, Hiroshima, Japan
| | - Yayoi Kimura
- Advanced Medical Research Center, Yokohama City University, Yokohama, Japan
| | - Itaru Hashimoto
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Kentaro Hara
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.,Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Yukio Maezawa
- Department of Surgery, Yokohama City University, Yokohama, Japan.,Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Hirohito Fujikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yukihiko Hiroshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Takanobu Yamada
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Hiroshi Tamagawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Naoto Yamamoto
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Takashi Ogata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan
| | - Hiroyuki Ito
- Department of Respiratory Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Soichiro Morinaga
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Wataru Yasui
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Science, Hiroshima, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Yohei Miyagi
- Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Takashi Oshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
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23
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Shah SH, Chen YF, Moss HE, Rubin DS, Joslin CE, Roth S. Predicting Risk of Perioperative Ischemic Optic Neuropathy in Spine Fusion Surgery: A Cohort Study Using the National Inpatient Sample. Anesth Analg 2020; 130:967-974. [PMID: 31490255 PMCID: PMC8098669 DOI: 10.1213/ane.0000000000004383] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Ischemic optic neuropathy (ION) is a rare complication of anesthesia and surgery that causes vision loss in spine fusion. We sought to develop a predictive model based on known preoperative risk factors for perioperative ION to guide patient and physician preoperative decision-making. METHODS In the National Inpatient Sample (NIS) for 1998-2012, discharges for posterior thoracic, lumbar, and sacral spine fusion were identified and classified by ION status. Variables were selected without weighting via variable clustering using Principal Component Analysis of Mixed Data (PCA-MIX). Hierarchical clustering with 4 clusters was performed, and the variable with largest squared loading in each cluster was chosen. By splitting our sample into a training and testing data set, we developed and internally validated a predictive model. The final model using variables known preoperatively was constructed to allow determination of relative and absolute risk of developing perioperative ION and was tested for calibration and discrimination. RESULTS The final predictive model based on hierarchical clustering contained 3 preoperative factors, age, male or female sex, and the presence of obstructive sleep apnea (OSA). The predictive model based on these factors had an area under the receiver operating characteristic curve (AUC) of 0.65 and good calibration. A score cutoff of >1 had 100% sensitivity, while score of 3 had 96.5% specificity. The highest estimated absolute risk (844.5/million) and relative risk of ION (46.40) was for a man, age 40-64 years, with OSA. CONCLUSIONS The predictive model could enable screening for patients at higher risk of ION to provide more accurate risk assessment and surgical and anesthetic planning for perioperative ION in spine fusion.
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Affiliation(s)
- Shikhar H Shah
- From the Department of Anesthesiology, Walter Reed National Military Medical Center, Washington, DC
| | - Yi-Fan Chen
- The Center for Clinical & Translational Sciences, University of Illinois at Chicago
| | - Heather E Moss
- Departments of Ophthalmology
- Neurology & Neurological Sciences, Stanford University, Palo Alto, California
| | - Daniel S Rubin
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois
| | - Charlotte E Joslin
- Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, Illinois
- Department of Epidemiology and Biostatistics, College of Public Health, University of Illinois at Chicago
| | - Steven Roth
- Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, Illinois
- Department of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois
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24
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Whitlock RP, Dieleman JM, Belley-Cote E, Vincent J, Zhang M, Devereaux P, Kalkman CJ, van Dijk D, Yusuf S. The Effect of Steroids in Patients Undergoing Cardiopulmonary Bypass: An Individual Patient Meta-Analysis of Two Randomized Trials. J Cardiothorac Vasc Anesth 2020; 34:99-105. [DOI: 10.1053/j.jvca.2019.06.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 11/11/2022]
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25
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Yoshikawa T, Aoyama T, Sakamaki K, Oshima T, Lin J, Zhang S, Sapari NS, Soong R, Tan I, Chan XB, Bottomley D, Hewitt LC, Arai T, Teh BT, Epstein D, Ogata T, Kameda Y, Miyagi Y, Tsuburaya A, Morita S, Grabsch HI, Tan P. Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer. J Cancer 2019; 10:5130-5138. [PMID: 31602266 PMCID: PMC6775596 DOI: 10.7150/jca.34741] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 06/25/2019] [Indexed: 12/14/2022] Open
Abstract
Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series.
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Affiliation(s)
- Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.,Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Toru Aoyama
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Kentaro Sakamaki
- Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan
| | - Takasi Oshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Joyce Lin
- Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore
| | - Shenli Zhang
- Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore
| | - Nur Sabrina Sapari
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
| | - Richie Soong
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
| | - Iain Tan
- Department of Pathology, National University of Singapore, Singapore, Singapore
| | - Xiu Bin Chan
- Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore
| | - Dan Bottomley
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Lindsay C Hewitt
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, NL
| | - Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - Bin Tean Teh
- Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore
| | - David Epstein
- Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore
| | - Takashi Ogata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yoichi Kameda
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Yohei Miyagi
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Akira Tsuburaya
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Heike I Grabsch
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.,Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, NL
| | - Patrick Tan
- Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore.,Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore.,Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
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26
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Jayaram A, Wingate A, Wetterskog D, Conteduca V, Khalaf D, Sharabiani MTA, Calabrò F, Barwell L, Feyerabend S, Grande E, Martinez-Carrasco A, Font A, Berruti A, Sternberg CN, Jones R, Lefresne F, Lahaye M, Thomas S, Joshi S, Shen D, Ricci D, Gormley M, Merseburger AS, Tombal B, Annala M, Chi KN, De Giorgi U, Gonzalez-Billalabeitia E, Wyatt AW, Attard G. Plasma Androgen Receptor Copy Number Status at Emergence of Metastatic Castration-Resistant Prostate Cancer: A Pooled Multicohort Analysis. JCO Precis Oncol 2019; 3:1900123. [PMID: 32923850 DOI: 10.1200/po.19.00123] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2019] [Indexed: 12/23/2022] Open
Abstract
PURPOSE Increases in androgen receptor (AR) copy number (CN) can be detected in plasma DNA when patients develop metastatic castration-resistant prostate cancer. We aim to evaluate the association between AR CN as a continuous variable and clinical outcome. PATIENTS AND METHODS PCR2023 was an international, multi-institution, open-label, phase II study of abiraterone acetate plus prednisolone (AAP) or abiraterone acetate plus dexamethasone that included plasma AR assessment as a predefined exploratory secondary end point. Plasma AR CN data (ClinicalTrials.gov identifier: NCT01867710) from this study (n = 133) were pooled with data from the following three other cohorts: cohort A, which was treated with either AAP or enzalutamide (n = 73); the PREMIERE trial (ClinicalTrials.gov identifier: NCT02288936) of biomarkers for enzalutamide (n = 94); and a phase II trial from British Columbia (ClinicalTrials.gov identifier: NCT02125357) that randomly assigned men to either AAP or enzalutamide (n = 201). The primary outcome measures for the biomarker analysis were overall survival and progression-free survival. RESULTS Using multivariable fractional polynomials analysis using Cox regression models, a nonlinear relationship between plasma AR CN and outcome was identified for overall survival, where initially for small incremental gains in CN there was a large added hazard ratio that plateaued at higher CN. The CN cut point associated with the highest local hazard ratio was 1.92. A similar nonlinear association was observed with progression-free survival. In an exploratory analysis of PCR2023, the time from start of long-term androgen-deprivation therapy to start of AAP or abiraterone acetate plus dexamethasone was significantly shorter in patients with plasma AR CN of 1.92 or greater than patients with plasma AR CN of less than 1.92 (43 v 130 weeks, respectively; P = .005). This was confirmed in cohort A (P = .003), the PREMIERE cohort (P = .03), and the British Colombia cohort (P = .003). CONCLUSION Patients with metastatic castration-resistant prostate cancer can be dichotomized by a plasma AR CN cut point of 1.92. Plasma AR CN value of 1.92 or greater identifies aggressive disease that is poorly responsive to AR targeting and is associated with a prior short response to primary androgen-deprivation therapy.
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Affiliation(s)
- Anuradha Jayaram
- University College London Cancer Institute, London, United Kingdom
| | - Anna Wingate
- University College London Cancer Institute, London, United Kingdom
| | | | - Vincenza Conteduca
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Meldola, Italy
| | - Daniel Khalaf
- Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada
| | | | | | - Lorraine Barwell
- University of Glasgow, The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
| | | | | | - Alberto Martinez-Carrasco
- Hospital Universitario Morales Meseguer, Biobanco Nodo 3, Instituto Murciano de Investigación Biosanitaria-Universidad de Murcia, Murcia, Spain
| | - Albert Font
- Institut Catala d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain
| | - Alfredo Berruti
- University of Brescia, Spedali Civili Hospital, Brescia, Italy
| | - Cora N Sternberg
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY
| | - Rob Jones
- University of Glasgow, The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
| | | | | | - Shibu Thomas
- Janssen Research and Development, Spring House, PA
| | | | - Dong Shen
- Janssen Research and Development, Spring House, PA
| | | | | | | | - Bertrand Tombal
- Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Matti Annala
- Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.,Prostate Cancer Research Center, University of Tampere, Tampere, Finland
| | - Kim N Chi
- Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.,BC Cancer Agency, Vancouver, British Columbia, Canada
| | - Ugo De Giorgi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Meldola, Italy
| | - Enrique Gonzalez-Billalabeitia
- Hospital Universitario Morales Meseguer, Biobanco Nodo 3, Instituto Murciano de Investigación Biosanitaria-Universidad de Murcia, Murcia, Spain
| | - Alexander W Wyatt
- Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada
| | - Gerhardt Attard
- University College London Cancer Institute, London, United Kingdom
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Ogłuszka M, Orzechowska M, Jędroszka D, Witas P, Bednarek AK. Evaluate Cutpoints: Adaptable continuous data distribution system for determining survival in Kaplan-Meier estimator. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2019; 177:133-139. [PMID: 31319941 DOI: 10.1016/j.cmpb.2019.05.023] [Citation(s) in RCA: 112] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 02/15/2019] [Accepted: 05/22/2019] [Indexed: 05/25/2023]
Abstract
BACKGROUND AND OBJECTIVE Growing evidence of transcriptional and metabolomic differentiation induced many studies which analyze such differentiation in context of outcome of disease progression, treatment or influence of many different factors affecting cellular and tissue metabolism. Particularly, cancer researchers are looking for new biomarkers that can serve as a diagnostic/prognostic factor and its further corresponding relationship regarding clinical effects. As a result of the increasing interest in use of dichotomization of continuous variables involving clinical or epidemiological data (gene expression, biomarkers, biochemical parameters, etc.) there is a large demand for cutoff point determination tools with simultaneous lack of software offering stratification of patients based on continuous and binary variables. Therefore, we developed "Evaluate Cutpoints" application offering wide set of statistical and graphical methods for cutpoint optimization enabling stratification of population into two or three groups. METHODS Application is based on R language including algorithms of packages such as survival, survMisc, OptimalCutpoints, maxstat, Rolr, ggplot2, GGally and plotly offering Kaplan-Meier plots and ROC curves with cutoff point determination. RESULTS All capabilities of Evaluate Cutpoints were illustrated with example analysis of estrogen, progesterone and human epidermal growth factor 2 receptors in breast cancer cohort. Through ROC curve the cutoff points were established for expression of ESR1, PGR and ERBB2 in correlation with their immunohistochemical status (cutoff: 1301.253, 243.35, 11,434.438, respectively; sensitivity: 94%, 85%, 64%, respectively; specificity: 93%, 86%, 91%, respectively). Through disease-free survival analysis we divided patients into two and three groups regarding expression of ESR1, PGR and ERBB2. Example algorithm cutp showed that lowered expression of ESR1 and ERBB2 was more favorable (HR = 2.07, p = 0.0412; HR = 2.79, p = 0.0777, respectively), whereas heightened PGR expression was correlated with better prognosis (HR = 0.192, p = 0.0115). CONCLUSIONS This work presents application Evaluate Cutpoints that is freely available to download at http://wnbikp.umed.lodz.pl/Evaluate-Cutpoints/. Currently, many softwares are used to split continuous variables such as Cutoff Finder and X-Tile, which offer distinct algorithms. Unlike them, Evaluate Cutpoints allows not only dichotomization of populations into groups according to continuous variables and binary variables, but also stratification into three groups as well as manual selection of cutoff point thus preventing potential loss of information.
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Affiliation(s)
- Magdalena Ogłuszka
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland
| | | | - Dorota Jędroszka
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland
| | - Piotr Witas
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland
| | - Andrzej K Bednarek
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.
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Beltrán L, González-Trejo S, Carmona-Herrera DD, Carrillo JF, Herrera-Goepfert R, Aiello-Crocifoglio V, Gallardo-Rincón D, Meléndez-Ponce NA, Ochoa-Carrillo FJ, Oñate-Ocaña LF. Prognostic Factors and Differences in Survival of Right and Left Colon Carcinoma: A STROBE Compliant Retrospective Cohort Study. Arch Med Res 2019; 50:63-70. [PMID: 31349955 DOI: 10.1016/j.arcmed.2019.05.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 04/05/2019] [Accepted: 05/24/2019] [Indexed: 01/09/2023]
Abstract
BACKGROUND Right-colon cancer (RCC) presents differences with Left-colon cancer (LCC) in terms of Overall survival (OS), but certain reports provide conflicting findings. Our objective is to define differences regarding prognostic factors in RCC and LCC by multivariate analysis. METHODS Retrospective cohort including patients treated from 1992-2016. The Kaplan-Meier and Cox models were used to define prognostic factors. RESULTS 871 patients had RCC and 748 LCC; mean age was 58.1. Location was associated with socioeconomic status, body mass, blood hemoglobin, serum albumin, lymphocyte count and Prognostic nutritional index (PNI). Distribution of TNM stages was similar between groups, as well as gender, age, surgical morbidity/mortality; 72.3% of RCC and 83.2% of LCC were well/moderately differentiated (p <0.0001). Mean surgical lymph-node retrieval was 19.3 (SD14.6) for RCC and 15.7 (SD13.1) for LCC (p <0.0001). Median OS was 5.2 (95% CI 3.9-6.5) for RCC, and 3.2 years (95% CI 2.1-4.4) for LCC (p = 0.426). OS was different between RCC and LCC by stratified analyses within PNI, TNM, differentiation and R classification. RCC presents different OS in stages IIIC, and IVB than LCC. CONCLUSION Differences between RCC and LCC were mainly by immunonutritional variables. Differences in OS were found after stratified analysis of PNI, TNM stages, differentiation degree, and R classification. Location of the neoplasm in the colon should be considered in the design of clinical trials in patients with colon cancer.
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Affiliation(s)
- Leonora Beltrán
- Instituto Nacional de Cancerologia, Ciudad de México, México
| | | | | | - José F Carrillo
- Instituto Nacional de Cancerologia, Ciudad de México, México
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Chang C, Hsieh MK, Chiang AJ, Tsai YH, Liu CC, Chen J. Methods for estimating the optimal number and location of cut points in multivariate survival analysis: a statistical solution to the controversial effect of BMI. Comput Stat 2019. [DOI: 10.1007/s00180-019-00908-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Chen Y, Huang J, He X, Gao Y, Mahara G, Lin Z, Zhang J. A novel approach to determine two optimal cut-points of a continuous predictor with a U-shaped relationship to hazard ratio in survival data: simulation and application. BMC Med Res Methodol 2019; 19:96. [PMID: 31072334 PMCID: PMC6507062 DOI: 10.1186/s12874-019-0738-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 04/22/2019] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND In clinical and epidemiological researches, continuous predictors are often discretized into categorical variables for classification of patients. When the relationship between a continuous predictor and log relative hazards is U-shaped in survival data, there is a lack of a satisfying solution to find optimal cut-points to discretize the continuous predictor. In this study, we propose a novel approach named optimal equal-HR method to discretize a continuous variable that has a U-shaped relationship with log relative hazards in survival data. METHODS The main idea of the optimal equal-HR method is to find two optimal cut-points that have equal log relative hazard values and result in Cox models with minimum AIC value. An R package 'CutpointsOEHR' has been developed for easy implementation of the optimal equal-HR method. A Monte Carlo simulation study was carried out to investigate the performance of the optimal equal-HR method. In the simulation process, different censoring proportions, baseline hazard functions and asymmetry levels of U-shaped relationships were chosen. To compare the optimal equal-HR method with other common approaches, the predictive performance of Cox models with variables discretized by different cut-points was assessed. RESULTS Simulation results showed that in asymmetric U-shape scenarios the optimal equal-HR method had better performance than the median split method, the upper and lower quantiles method, and the minimum p-value method regarding discrimination ability and overall performance of Cox models. The optimal equal-HR method was applied to a real dataset of small cell lung cancer. The real data example demonstrated that the optimal equal-HR method could provide clinical meaningful cut-points and had good predictive performance in Cox models. CONCLUSIONS In general, the optimal equal-HR method is recommended to discretize a continuous predictor with right-censored outcomes if the predictor has an asymmetric U-shaped relationship with log relative hazards based on Cox regression models.
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Affiliation(s)
- Yimin Chen
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Jialing Huang
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Xianying He
- National Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Yongxiang Gao
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Gehendra Mahara
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhuochen Lin
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Jinxin Zhang
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
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Luvián-Morales J, González-Trejo S, Carrillo JF, Herrera-Goepfert R, Aiello-Crocifoglio V, Gallardo-Rincón D, Ochoa-Carrillo FJ, Oñate-Ocaña LF. Association of the prognostic nutritional index and overall survival in patients with colorectal cancer: A STROBE compliant retrospective cohort study. Cancer Med 2019; 8:3379-3388. [PMID: 31069966 PMCID: PMC6601598 DOI: 10.1002/cam4.2212] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 04/04/2019] [Accepted: 04/14/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The TNM classification does not completely reflect the prognosis of patients with colorectal cancer (CRC). Several clinical factors have been used to increase its prognostic value, but factors pertaining to the patient's immunonutritional status have not usually been addressed. The aim of this study is to evaluate the role of Prognostic nutritional index (PNI) and other well-known prognostic factors by multivariate analysis in a cohort of patients with CRC. METHODS This is a retrospective cohort study of consecutive patients with CRC managed in a cancer center between January 1992 and December 2016. Cox's model was used to define the association of the PNI and other factors with Overall survival (OS). RESULTS A total of 3301 patients were included: 47.7% were female and 52.3% were male, with a mean age of 58.7 years. By bivariate analysis, PNI was strongly associated with OS (Risk ratio [RR] 0.968, 95% Confidence interval [CI] 0.962-0.974; P < 0.001). On multivariate analysis, PNI was an independent explanatory variable (as continuous variable and as categorized variable; RR 0.732, 95% CI 0.611-0.878; RR 0.656, 95% CI 0.529-0.813 and RR 0.646, 95% CI 0.521-0.802, for quintiles 2, 3, and 4-5, respectively); a biological gradient effect was demonstrated. The final prognostic model included PNI, location of the neoplasia in the colorectum, basal hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, TNM stage, differentiation degree, R classification, and postoperative complications. CONCLUSIONS PNI is a significant and independent prognostic factor in patients with CRC. Its prognostic value adds precision to the TNM staging system including specific subgroups of patients with CRC; it should be evaluated in prospective clinical studies.
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Affiliation(s)
- Julissa Luvián-Morales
- Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | - Sagrario González-Trejo
- Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | - José F Carrillo
- Subdirección de Cirugía, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | | | | | - Dolores Gallardo-Rincón
- Departamento de Oncología Médica, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | | | - Luis F Oñate-Ocaña
- Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
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Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv 2019; 2:909-922. [PMID: 29678809 DOI: 10.1182/bloodadvances.2017014464] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 02/01/2018] [Indexed: 12/17/2022] Open
Abstract
Slow immune reconstitution is a major obstacle to the successful use of allogeneic hematopoietic cell transplantation (allo-HCT). As matched sibling donor (MSD) allo-HCT is regarded as the gold standard, we evaluated the pace of immune reconstitution in 157 adult recipients of reduced-intensity conditioning followed by MSD peripheral blood HCT (n = 68) and compared these to recipients of umbilical cord blood (UCB; n = 89). At day 28, UCB recipients had fewer natural killer (NK) cells than MSD recipients, but thereafter, NK cell numbers (and their subsets) were higher in UCB recipients. During the first 6 months to 1 year after transplant, UCB recipients had slower T-cell subset recovery, with lower numbers of CD3+, CD8+, CD8+ naive, CD4+ naive, CD4+ effector memory T, regulatory T, and CD3+CD56+ T cells than MSD recipients. Notably, B-cell numbers were higher in UCB recipients from day 60 to 1 year. Bacterial and viral infections were more frequent in UCB recipients, yet donor type had no influence on treatment-related mortality or survival. Considering all patients at day 28, lower numbers of total CD4+ T cells and naive CD4+ T cells were significantly associated with increased infection risk, treatment-related mortality, and chronic graft-versus-host disease (GVHD). Patients with these characteristics may benefit from enhanced or prolonged infection surveillance and prophylaxis as well as immune reconstitution-accelerating strategies.
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Diniz MA, Tighiouart M, Rogatko A. Comparison between continuous and discrete doses for model based designs in cancer dose finding. PLoS One 2019; 14:e0210139. [PMID: 30625194 PMCID: PMC6326565 DOI: 10.1371/journal.pone.0210139] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 12/18/2018] [Indexed: 11/18/2022] Open
Abstract
Despite of an extensive statistical literature showing that discretizing continuous variables results in substantial loss of information, categorization of continuous variables has been a common practice in clinical research and in cancer dose finding (phase I) clinical trials. The objective of this study is to quantify the loss of information incurred by using a discrete set of doses to estimate the maximum tolerated dose (MTD) in phase I trials, instead of a continuous dose support. Escalation With Overdose Control and Continuous Reassessment Method were used because they are model-based designs where dose can be specified either as continuous or as a set of discrete levels. Five equally spaced sets of doses with different interval lengths and three sample sizes with sixteen scenarios were evaluated to compare the operating characteristics between continuous and discrete dose designs by Monte Carlo simulation. Loss of information was quantified by safety and efficiency measures. We conclude that if there is insufficient knowledge about the true MTD value, as commonly happens in phase I clinical trials, a continuous dose scheme minimizes information loss. If one is required to implement a design using discrete doses, then a scheme with 9 to 11 doses may yield similar results to the continuous dose scheme.
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Affiliation(s)
- Márcio Augusto Diniz
- Biostatistics and Bionformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, United States of America
- * E-mail:
| | - Mourad Tighiouart
- Biostatistics and Bionformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, United States of America
| | - André Rogatko
- Biostatistics and Bionformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, United States of America
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Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill Children and the Impact of Delaying Parenteral Nutrition. Pediatr Crit Care Med 2018; 19:1120-1129. [PMID: 30234740 PMCID: PMC6282934 DOI: 10.1097/pcc.0000000000001734] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES In the Early versus Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial, delaying parenteral nutrition to beyond day 7 (late parenteral nutrition) was clinically superior to supplemental parenteral nutrition initiated within 24 hours (early parenteral nutrition), but resulted in a higher rise in bilirubin. We aimed to document prevalence and prognostic value of abnormal liver tests in the PICU and the impact hereon of withholding early parenteral nutrition. DESIGN Preplanned secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial. Total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase plasma concentrations were measured systematically in PICU. Liver test analyses were adjusted for baseline characteristics including severity of illness. SETTING Three PICUs in Belgium, the Netherlands, and Canada. PATIENTS As neonatal jaundice was considered a confounder, only the 1,231 of the 1,440 Early versus Late Parenteral Nutrition in the Pediatric ICU-patients 28 days to 17 years old were included. INTERVENTIONS Late parenteral nutrition as compared with early parenteral nutrition. MEASUREMENTS AND MAIN RESULTS During the first seven PICU days, the prevalence of cholestasis (> 2 mg/dL [34.2 μmol/L] bilirubin) ranged between 3.8% and 4.9% and of hypoxic hepatitis (≥ 20-fold upper limit of normality for alanine aminotransferase and aspartate aminotransferase) between 0.8% and 2.2%, both unaffected by the use of parenteral nutrition. Throughout the first week in PICU plasma bilirubin concentrations were higher in late parenteral nutrition patients (p < 0.05), but became comparable to early parenteral nutrition patients as soon as parenteral nutrition was started on day 8. Plasma concentrations of gamma-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were unaffected by parenteral nutrition. High day 1 plasma concentrations of gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase (p ≤ 0.01), but not alkaline phosphatase, were independent risk factors for PICU mortality. Day 1 plasma bilirubin concentrations displayed a U-shaped association with PICU mortality, with higher mortality associated with bilirubin less than 0.20 mg/dL and greater than 0.76 mg/dL (< 3.42 μmol/L and > 13 μmol/L) (p ≤ 0.01). CONCLUSIONS Overt cholestasis and hypoxic hepatitis were rare and unrelated to the nutritional strategy. However, withholding parenteral nutrition up to 1 week in PICU increased plasma bilirubin. A mild elevation of bilirubin on the first PICU day was associated with lower risk of death and may reflect a stress response, rather than true cholestasis.
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Liu X, Chen L, Zhang T. Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma. Cancer Control 2018; 25:1073274818778001. [PMID: 29843532 PMCID: PMC6028180 DOI: 10.1177/1073274818778001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.
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Affiliation(s)
- Xi Liu
- 1 Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Lei Chen
- 1 Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Tao Zhang
- 1 Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China
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Punthakee Z, Iglesias PP, Alonso-Coello P, Gich I, India I, Malaga G, Jover RD, Gerstein HC, Devereaux PJ. Association of preoperative glucose concentration with myocardial injury and death after non-cardiac surgery (GlucoVISION): a prospective cohort study. Lancet Diabetes Endocrinol 2018; 6:790-797. [PMID: 30057170 PMCID: PMC7028328 DOI: 10.1016/s2213-8587(18)30205-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 06/14/2018] [Accepted: 06/28/2018] [Indexed: 01/08/2023]
Abstract
BACKGROUND Myocardial injury after non-cardiac surgery (MINS) is the most common perioperative cardiovascular complication and is independently associated with 30-day mortality. We aimed to assess the association between preoperative glucose concentration and postoperative MINS and mortality. METHODS The VISION study is a prospective cohort study done at 12 centres in eight countries. Patients aged 45 years or older who required at least one overnight hospital admission for non-cardiac surgery were enrolled from Aug 6, 2007, to Jan 11, 2011. In the GlucoVISION analysis, we assessed the relations between preoperative casual or fasting glucose concentration and MINS within 3 days after surgery using logistic regression, and 30-day mortality using Cox proportional regression, in people with and without diabetes. FINDINGS 11 954 patients were included in this analysis, of whom 2809 (23%) had diabetes. Within the first three postoperative days, MINS occurred in 813 (7%) patients. 249 (2%) patients died by day 30. More patients with diabetes had MINS (odds ratio [OR] 1·98 [95% CI 1·70-2·30]; p<0·0001), and died (OR 1·41 [1·08-1·86]; p=0·016) than did patients without diabetes. Casual glucose concentrations were associated with MINS in all patients (adjusted OR 1·06 [1·04-1·09] per 1 mmol/L increment in glucose; p=0·0003), and with death in patients without diabetes (adjusted hazard ratio [HR] 1·13 [95% CI 1·05-1·23] per mmol/L; p=0·002). We noted a progressive relation between unadjusted fasting glucose concentration and both MINS (OR 1·14 [1·08-1·20] per mmol/L; p<0·0001), driven by the effect in the subgroup without previous diabetes (pinteraction=0·025), and 30-day mortality (HR 1·10 [1·02-1·19] per mmol/L; p=0·013). For patients without diabetes, casual glucose of more than 6·86 mmol/L and fasting glucose of more than 6·41 mmol/L predicted MINS (OR 1·71 [1·36-2·15]; p<0·0001, and OR 2·71 [1·85-3·98]; p<0·0001, respectively). For patients with diabetes, only casual glucose concentration more than 7·92 mmol/L predicted MINS (OR 1·47 [1·10-1·96]; p=0·0096). INTERPRETATION Preoperative glucose concentration, particularly casual glucose concentration, predicts risk for postoperative cardiovascular outcomes, especially in patients without diabetes. FUNDING Full funding sources listed at the end of the paper (see Acknowledgments).
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Affiliation(s)
- Zubin Punthakee
- McMaster University and Population Health Research Institute, Hamilton, ON, Canada.
| | - Pilar Paniagua Iglesias
- Servicio de Anestesiología y Reanimación, Instituto de Investigación Biomédica (IIB Sant Pau), Barcelona, Spain.
| | - Pablo Alonso-Coello
- Centro Cochrane Iberoamericano, Instituto de Investigación Biomédica (IIB Sant Pau-CIBERESP), Barcelona, Spain
| | - Ignasi Gich
- Department of Clinical Epidemiology and Public Health, HSCSP CIBER de Salud Mental (CIBERSAM), Barcelona, Spain
| | - Inmaculada India
- Servicio de Anestesiología y Reanimación, Instituto de Investigación Biomédica (IIB Sant Pau), Barcelona, Spain
| | | | - Ruben Diaz Jover
- Servicio de Anestesiología y Reanimación, Instituto de Investigación Biomédica (IIB Sant Pau), Barcelona, Spain
| | - Hertzel C Gerstein
- McMaster University and Population Health Research Institute, Hamilton, ON, Canada
| | - P J Devereaux
- McMaster University and Population Health Research Institute, Hamilton, ON, Canada
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Holtan SG, DeFor TE, Panoskaltsis-Mortari A, Khera N, Levine JE, Flowers MED, Lee SJ, Inamoto Y, Chen GL, Mayer S, Arora M, Palmer J, Cutler CS, Arai S, Lazaryan A, Newell LF, Jagasia MH, Pusic I, Wood WA, Renteria AS, Yanik G, Hogan WJ, Hexner E, Ayuk F, Holler E, Bunworasate U, Efebera YA, Ferrara JLM, Pidala J, Howard A, Wu J, Bolaños-Meade J, Ho V, Alousi A, Blazar BR, Weisdorf DJ, MacMillan ML. Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802. Blood Adv 2018; 2:1882-1888. [PMID: 30087106 PMCID: PMC6093743 DOI: 10.1182/bloodadvances.2018017343] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 06/26/2018] [Indexed: 01/07/2023] Open
Abstract
Amphiregulin (AREG) is an epidermal growth factor receptor ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously reported that circulating AREG is elevated in late-onset aGVHD (occurring after 100 days posttransplant), but its clinical relevance in the context of aGVHD risk is unknown. We measured AREG in 251 aGVHD onset blood samples from Blood and Marrow Clinical Trials Network (BMT CTN) primary treatment trials and determined their association with GVHD severity, day 28 complete or partial response (CR/PR) to first-line therapy, overall survival (OS), and nonrelapse mortality (NRM). Every doubling of plasma AREG was associated with a 33% decrease in the odds of day 28 CR/PR (odds ratio [OR], 0.67; P < .01). An AREG threshold of 33 pg/mL or greater divided patients with Minnesota standard-risk (SR) aGVHD into a distinct group with a significantly lower likelihood of: day 28 CR/PR (72% vs 85%; P = .02); greater 2-year NRM (42% vs 15%; P < .01); and inferior OS (40% vs 66%; P < .01). High AREG ≥ 33 pg/mL also stratified patients with Minnesota high-risk (HR) aGVHD: day 28 CR/PR (54% vs 83%; P = .03) and 2-year NRM (53% vs 11%; P < .01), with a trend toward inferior 2-year OS (37% vs 60%; P = .09). High-circulating AREG (≥33 pg/mL) reclassifies patients into HR subgroups and thereby further refines the Minnesota aGVHD clinical risk score.
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Affiliation(s)
- Shernan G Holtan
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN
| | - Todd E DeFor
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN
| | | | | | - John E Levine
- Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - Mary E D Flowers
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Stephanie J Lee
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Yoshihiro Inamoto
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - George L Chen
- Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY
| | - Sebastian Mayer
- Department of Medicine, Weill Cornell Medical Center, New York, NY
| | - Mukta Arora
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN
| | | | - Corey S Cutler
- Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
| | - Sally Arai
- Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA
| | - Aleksandr Lazaryan
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN
| | - Laura F Newell
- Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR
| | - Madan H Jagasia
- Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Iskra Pusic
- Medical Oncology, Washington University Medical Center, St. Louis, MO
| | - William A Wood
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
| | - Anne S Renteria
- Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gregory Yanik
- Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI
| | - William J Hogan
- Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN
| | - Elizabeth Hexner
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Center, Hamburg-Eppendorf, Germany
| | - Ernst Holler
- Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany
| | - Udomsak Bunworasate
- Blood and Marrow Transplantation Program, Chulalongkorn University, Bangkok, Thailand
| | - Yvonne A Efebera
- Blood and Marrow Transplantation Program, The Ohio State University, Columbus, OH
| | - James L M Ferrara
- Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - Joseph Pidala
- Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Alan Howard
- National Marrow Donor Program, Minneapolis, MN
| | - Juan Wu
- The EMMES Corporation, Rockville, MD
| | - Javier Bolaños-Meade
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; and
| | - Vincent Ho
- Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA
| | | | - Bruce R Blazar
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN
| | - Daniel J Weisdorf
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN
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Sawazaki S, Oshima T, Sakamaki K, Aoyama T, Sato T, Shiozawa M, Yoshikawa T, Rino Y, Imada T, Masuda M. Clinical Significance of Tensin 4 Gene Expression in Patients with Gastric Cancer. ACTA ACUST UNITED AC 2018; 31:1065-1071. [PMID: 29102927 DOI: 10.21873/invivo.11171] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 08/14/2017] [Accepted: 08/22/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative resection and adjuvant chemotherapy. Tensin 4 (TNS4), a cell adhesion factor, is associated with cancer-cell motility and migration. PATIENTS AND METHODS We examined the clinical significance of TNS4 gene expression in 134 patients with stage II/III gastric cancer who underwent adjuvant chemotherapy with S-1. TNS4 gene expression in surgical specimens was measured by quantitative reverse-transcription polymerase chain reaction (RT-PCR). RESULTS TNS4 gene expression levels were significantly higher in cancer tissue than in adjacent normal mucosa. High TNS4 gene expression was associated with significantly poorer 5-year overall survival than was low expression. On multivariate analysis, TNS4 gene expression was an independent prognostic factor. CONCLUSION Overexpression of the TNS4 gene is a useful independent predictor of outcomes in patients with stage II/III gastric cancer who undergo surgery and receive adjuvant chemotherapy with S-1.
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Affiliation(s)
- Sho Sawazaki
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Takashi Oshima
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Kentaro Sakamaki
- Department of Biostatistics, Yokohama City University Medical Center, Yokohama, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Tsutomu Sato
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Takaki Yoshikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Toshio Imada
- Department of Surgery, Saiseikai Yokohama-shi Nanbu Hospital, Yokohama, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, Yokohama, Japan
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Suzuki Y, Oshima T, Yoshihara K, Sakamaki K, Aoyama T, Cho H, Shiozawa M, Yoshikawa T, Rino Y, Imada T, Masuda M. Clinical significance of secreted protein, acidic and cysteine-rich gene expression in patients with stage II/III gastric cancer following curative resection and adjuvant chemotherapy with S-1. Oncol Lett 2018; 15:7335-7343. [PMID: 29725448 DOI: 10.3892/ol.2018.8248] [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: 07/26/2016] [Accepted: 12/20/2017] [Indexed: 11/06/2022] Open
Abstract
The standard treatment for stage II/III gastric cancer is surgical resection followed by adjuvant chemotherapy with fluoropyrimidine anticancer agents, including S-1. The protein, secreted protein, acidic and cysteine-rich (SPARC), promotes angiogenesis, and the proliferation and migration of cancer cells. The present study evaluated the significance of expression of the SPARC gene in patients with stage II/III gastric cancer who had undergone surgical resection and adjuvant chemotherapy with S-1. In the present study, reverse transcription-quantitative polymerase chain reaction was performed in order to quantify mRNA expression levels of SPARC in cancer tissues and adjacent normal mucosa obtained from 134 patients with stage II/III gastric cancer who had undergone surgical resection followed by adjuvant chemotherapy with S-1. The mRNA expression level of SPARC was significantly higher in cancer tissues than in adjacent normal mucosa (P=0.0012). Additionally, the 5-year overall survival rate was significantly poorer in patients with high SPARC gene expression than in those with low expression (P<0.0001). Furthermore, multivariate analysis indicated that high SPARC mRNA expression was a significant predictor of poorer survival in patients with stage II/III gastric cancer who had undergone surgical resection and adjuvant chemotherapy with S-1 (HR, 5.347; P<0.0001). Therefore, high expression of the SPARC gene may be a useful predictor of outcomes in patients with stage II/III gastric cancer, who have received treatment involving surgical resection and adjuvant chemotherapy with S-1.
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Affiliation(s)
- Yoshihiro Suzuki
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Takashi Oshima
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Kazue Yoshihara
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Kentaro Sakamaki
- Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Haruhiko Cho
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Manabu Shiozawa
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Takaki Yoshikawa
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
| | - Toshio Imada
- Department of Surgery, Yokohama City Nanbu Hospital, Yokohama, Kanagawa 234-0054, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
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40
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Katayama Y, Oshima T, Sakamaki K, Aoyama T, Sato T, Masudo K, Shiozawa M, Yoshikawa T, Rino Y, Imada T, Masuda M. Clinical Significance of INHBA Gene Expression in Patients with Gastric Cancer who Receive Curative Resection Followed by Adjuvant S-1 Chemotherapy. ACTA ACUST UNITED AC 2018; 31:565-571. [PMID: 28652421 DOI: 10.21873/invivo.11095] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Revised: 05/14/2017] [Accepted: 05/15/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND Standard treatment for stage II/III gastric cancer is curative resection followed by adjuvant chemotherapy. However, the five-year survival remains unsatisfactory. Inhibin βA (INHBA) has been reported to be associated with cancer cell proliferation and chemoresistance. PATIENTS AND METHODS We studied the clinical significance of INHBA gene expression in 134 patients with stage II/III gastric cancer who received adjuvant chemotherapy with S-1. INHBA expression of specimens of cancer tissue and adjacent normal mucosa was measured by quantitative real-time, reverse-transcription polymerase chain reaction (RT-PCR). RESULTS INHBA expression levels were significantly higher in cancer tissue than in adjacent normal mucosa. High INHBA expression was associated with significantly poorer 5-year survival than was low expression. On multivariate analysis, INHBA expression was an independent prognostic factor. CONCLUSION INHBA gene expression in gastric cancer tissue is considered a useful independent predictor of outcomes in patients with stage II/III gastric cancer who receive adjuvant chemotherapy with S-1.
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Affiliation(s)
- Yusuke Katayama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Takashi Oshima
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Kentaro Sakamaki
- Department of Biostatistics, Yokohama City University Medical Center, Yokohama, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Tsutomu Sato
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Katsuhiko Masudo
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Takaki Yoshikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Toshio Imada
- Department of Surgery, Saisei-kai Yokohama-shi Nanbu Hospital, Yokohama, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, Yokohama, Japan
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Chapalain X, Huet O. Post-operative high sensitivity troponin T (hsTnT): toward an extending use for diagnosis and management of myocardial injury after noncardiac surgery? J Thorac Dis 2017; 9:2231-2234. [PMID: 28932512 DOI: 10.21037/jtd.2017.06.146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Xavier Chapalain
- Department of Anesthesiology and Intensive Care Medicine, Brest University Hospital, Brest cedex, France
| | - Olivier Huet
- Department of Anesthesiology and Intensive Care Medicine, Brest University Hospital, Brest cedex, France
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Prince Nelson SL, Ramakrishnan V, Nietert PJ, Kamen DL, Ramos PS, Wolf BJ. An evaluation of common methods for dichotomization of continuous variables to discriminate disease status. COMMUN STAT-THEOR M 2017; 46:10823-10834. [PMID: 29962658 DOI: 10.1080/03610926.2016.1248783] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Dichotomization of continuous variables to discriminate a dichotomous outcome is often useful in statistical applications. If a true threshold for a continuous variable exists, the challenge is identifying it. This paper examines common methods for dichotomization to identify which ones recover a true threshold. We provide mathematical and numeric proofs demonstrating that maximizing the odds ratio, Youden's statistic, Gini Index, chi-square statistic, relative risk and kappa statistic all theoretically recover a true threshold. A simulation study evaluating the ability of these statistics to recover a threshold when sampling from a population indicates that maximizing the chi-square statistic and Gini Index have the smallest bias and variability when the probability of being larger than the threshold is small while maximizing Kappa or Youden's statistics is best when this probability is larger. Maximizing odds ratio is the most variable and biased of the methods.
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Affiliation(s)
- Sybil L Prince Nelson
- Department of Public Health Sciences, Medical Univeristy of South Carolina Charleston, South Carolina, 29425, U.S.A.
| | | | - Paul J Nietert
- Department of Public Health Sciences, Medical Univeristy of South Carolina
| | - Diane L Kamen
- Department of Medicine, Medical Univeristy of South Carolina
| | - Paula S Ramos
- Department of Medicine, Medical Univeristy of South Carolina
| | - Bethany J Wolf
- Department of Public Health Sciences, Medical Univeristy of South Carolina Charleston, South Carolina 29425, U.S.A.
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43
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Ustun C, DeFor TE, Rashidi A, Devine S, Miller J, Weisdorf D. Time-to-Event Ratio to Predict Outcome in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation? Biol Blood Marrow Transplant 2017; 23:1804-1808. [PMID: 28688918 DOI: 10.1016/j.bbmt.2017.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 06/20/2017] [Indexed: 11/30/2022]
Affiliation(s)
- Celalettin Ustun
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
| | - Todd E DeFor
- Biostatistics and Bioinformatics, University of Minnesota, Minneapolis, Minnesota
| | - Armin Rashidi
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Steven Devine
- Division of Hematology, Ohio State University, Columbus, Ohio
| | - Jeffrey Miller
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Daniel Weisdorf
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
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44
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Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, Fernandez-Perez MP, Jayaram A, Salvi S, Castellano D, Romanel A, Lolli C, Casadio V, Gurioli G, Amadori D, Font A, Vazquez-Estevez S, González del Alba A, Mellado B, Fernandez-Calvo O, Méndez-Vidal MJ, Climent MA, Duran I, Gallardo E, Rodriguez A, Santander C, Sáez MI, Puente J, Gasi Tandefelt D, Wingate A, Dearnaley D, Demichelis F, De Giorgi U, Gonzalez-Billalabeitia E, Attard G. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann Oncol 2017; 28:1508-1516. [PMID: 28472366 PMCID: PMC5834043 DOI: 10.1093/annonc/mdx155] [Citation(s) in RCA: 207] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER NCT02288936 (PREMIERE trial).
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Androstenes/adverse effects
- Androstenes/therapeutic use
- Antineoplastic Agents, Hormonal/adverse effects
- Antineoplastic Agents, Hormonal/therapeutic use
- Benzamides
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/genetics
- Circulating Tumor DNA/blood
- Circulating Tumor DNA/genetics
- DNA Mutational Analysis
- Disease Progression
- Disease-Free Survival
- Europe
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Multiplex Polymerase Chain Reaction
- Multivariate Analysis
- Mutation
- Nitriles
- Odds Ratio
- Patient Selection
- Phenylthiohydantoin/adverse effects
- Phenylthiohydantoin/analogs & derivatives
- Phenylthiohydantoin/therapeutic use
- Precision Medicine
- Predictive Value of Tests
- Proportional Hazards Models
- Prospective Studies
- Prostatic Neoplasms, Castration-Resistant/blood
- Prostatic Neoplasms, Castration-Resistant/drug therapy
- Prostatic Neoplasms, Castration-Resistant/genetics
- Prostatic Neoplasms, Castration-Resistant/mortality
- Receptors, Androgen/blood
- Receptors, Androgen/genetics
- Risk Factors
- Time Factors
- Treatment Outcome
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Affiliation(s)
- V. Conteduca
- Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - D. Wetterskog
- Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
| | - M. T. A. Sharabiani
- Research Data Management and Statistics Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - E. Grande
- Department of Medical Oncology, Hospital Ramón y Cajal, Madrid
| | - M. P. Fernandez-Perez
- Department of Hematology & Medical Oncology, Hospital Universitario Morales Meseguer, IMIB-Universidad de Murcia, Murcia
| | - A. Jayaram
- Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
- Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - S. Salvi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - D. Castellano
- Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - A. Romanel
- Centre for Integrative Biology, University of Trento, Trento, Italy
| | - C. Lolli
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - V. Casadio
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - G. Gurioli
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - D. Amadori
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - A. Font
- Oncology Unit, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona
| | | | | | - B. Mellado
- Department of Medical Oncology, IDIBAPS Hospital Clinic, Barcelona
| | | | - M. J. Méndez-Vidal
- Department of Medical Oncology, Hospital Universitario Reina Sofía, Córdoba
| | - M. A. Climent
- Department of Medical Oncology, Instituto Valenciano de Oncología Valencia, Valencia
| | - I. Duran
- Department of Medical Oncology, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla
| | - E. Gallardo
- Department of Medical Oncology, H.U. Parc Taulí, Sabadell, Barcelona
| | - A. Rodriguez
- Department of Medical Oncology, Hospital de León, León
| | - C. Santander
- Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza
| | - M. I. Sáez
- Department of Medical Oncology, Hospital Regional y Hospital Virgen de la Victoria, Malaga
| | - J. Puente
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain
| | - D. Gasi Tandefelt
- Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
| | - A. Wingate
- Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
| | - D. Dearnaley
- Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
| | | | | | - F. Demichelis
- Centre for Integrative Biology, University of Trento, Trento, Italy
- Institute for Precision Medicine, Weill Cornell Medicine, New York, USA
| | - U. De Giorgi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - E. Gonzalez-Billalabeitia
- Department of Hematology & Medical Oncology, Hospital Universitario Morales Meseguer, IMIB-Universidad de Murcia, Murcia
- Department of Medical Oncology, Universidad Católica San Antonio de Murcia-UCAM, Murcia, Spain
| | - G. Attard
- Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
- Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK
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Mollayeva T, Cassidy JD, Shapiro CM, Mollayeva S, Colantonio A. Concussion/mild traumatic brain injury-related chronic pain in males and females: A diagnostic modelling study. Medicine (Baltimore) 2017; 96:e5917. [PMID: 28207508 PMCID: PMC5319497 DOI: 10.1097/md.0000000000005917] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 12/23/2016] [Accepted: 12/28/2016] [Indexed: 12/31/2022] Open
Abstract
Pain is an unpleasant, complex, and perceived experience that places a significant burden on patients and clinicians. Its severity may be mediated by emotion, attitude, and environmental influences, and pain may be expressed differently in males and females. Traumatic brain injury (TBI) is frequently associated with chronic pain. This diagnostic modeling study examined sex differences in the construct of chronic pain in patients with delayed recovery from concussion/mild traumatic brain injury (mTBI).Data were collected from standardized questionnaires, neuroimaging records, and comprehensive clinical assessments. Bivariate associations were calculated using the Spearman correlation coefficient or analysis of variance. We established sex-specific stepwise multivariate linear regression models of factors associated with pain.Of the 94 participants diagnosed with mTBI (the mean age was 45.20 ± 9.94 years; 61.2% were males; the median time since injury was 197 days [interquartile range 139-416]), head/neck, and bodily pain were reported by 93% and 64%, respectively. No sex differences were identified in pain frequencies or severity. Pain was significantly associated with certain socio-demographic, injury-related, behavioral, and clinical variables. In the multivariable regression analysis, several determinants explained 60% of the pain variance in males and 46% in females.Pain is common in patients with delayed recovery from mTBI and is significantly associated with potentially modifiable clinical and nonclinical variables. Examining the multidimensional construct of pain in concussion/mTBI through a sex lens garners new directions for future longitudinal research on the pain mechanisms involved in postconcussion syndrome.
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Affiliation(s)
- Tatyana Mollayeva
- Rehabilitation Sciences Institute, Faculty of Medicine
- Department of Occupational Science and Occupational Therapy, University of Toronto
- Toronto Rehabilitation Institute
| | - J. David Cassidy
- Division of Health Care and Outcomes Research, University Health Network
- Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto
| | - Colin M. Shapiro
- Toronto Western Hospital, University Health Network
- Youthdale Child & Adolescent Sleep Clinic
| | - Shirin Mollayeva
- Department of Biology, University of Toronto, Mississauga, Ontario, Canada
| | - Angela Colantonio
- Rehabilitation Sciences Institute, Faculty of Medicine
- Department of Occupational Science and Occupational Therapy, University of Toronto
- Toronto Rehabilitation Institute
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Fong Y, Di C, Huang Y, Gilbert PB. Model-robust inference for continuous threshold regression models. Biometrics 2016; 73:452-462. [PMID: 27858965 DOI: 10.1111/biom.12623] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2016] [Revised: 10/01/2016] [Accepted: 10/01/2016] [Indexed: 11/30/2022]
Abstract
We study threshold regression models that allow the relationship between the outcome and a covariate of interest to change across a threshold value in the covariate. In particular, we focus on continuous threshold models, which experience no jump at the threshold. Continuous threshold regression functions can provide a useful summary of the association between outcome and the covariate of interest, because they offer a balance between flexibility and simplicity. Motivated by collaborative works in studying immune response biomarkers of transmission of infectious diseases, we study estimation of continuous threshold models in this article with particular attention to inference under model misspecification. We derive the limiting distribution of the maximum likelihood estimator, and propose both Wald and test-inversion confidence intervals. We evaluate finite sample performance of our methods, compare them with bootstrap confidence intervals, and provide guidelines for practitioners to choose the most appropriate method in real data analysis. We illustrate the application of our methods with examples from the HIV-1 immune correlates studies.
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Affiliation(s)
- Youyi Fong
- Fred Hutchinson Cancer Research Center, Seattle Washington 98109, U.S.A
| | - Chongzhi Di
- Fred Hutchinson Cancer Research Center, Seattle Washington 98109, U.S.A
| | - Ying Huang
- Fred Hutchinson Cancer Research Center, Seattle Washington 98109, U.S.A
| | - Peter B Gilbert
- Fred Hutchinson Cancer Research Center, Seattle Washington 98109, U.S.A
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Gómez I, Ribelles N, Franco L, Alba E, Jerez JM. Supervised discretization can discover risk groups in cancer survival analysis. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2016; 136:11-19. [PMID: 27686699 DOI: 10.1016/j.cmpb.2016.08.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 07/07/2016] [Accepted: 08/12/2016] [Indexed: 06/06/2023]
Abstract
Discretization of continuous variables is a common practice in medical research to identify risk patient groups. This work compares the performance of gold-standard categorization procedures (TNM+A protocol) with that of three supervised discretization methods from Machine Learning (CAIM, ChiM and DTree) in the stratification of patients with breast cancer. The performance for the discretization algorithms was evaluated based on the results obtained after applying standard survival analysis procedures such as Kaplan-Meier curves, Cox regression and predictive modelling. The results show that the application of alternative discretization algorithms could lead the clinicians to get valuable information for the diagnosis and outcome of the disease. Patient data were collected from the Medical Oncology Service of the Hospital Clínico Universitario (Málaga, Spain) considering a follow up period from 1982 to 2008.
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Affiliation(s)
- Iván Gómez
- Computer Science Department, University of Málaga, Campus de Teatinos S/N, 29071 Málaga, Spain; Málaga Biomedical Research Institute (IBIMA), Málaga, Spain.
| | - Nuria Ribelles
- Málaga Biomedical Research Institute (IBIMA), Málaga, Spain; Virgen de la Victoria Oncology Service, Málaga, Campus de Teatinos S/N, 29071 Málaga, Spain
| | - Leonardo Franco
- Computer Science Department, University of Málaga, Campus de Teatinos S/N, 29071 Málaga, Spain; Málaga Biomedical Research Institute (IBIMA), Málaga, Spain
| | - Emilio Alba
- Málaga Biomedical Research Institute (IBIMA), Málaga, Spain; Virgen de la Victoria Oncology Service, Málaga, Campus de Teatinos S/N, 29071 Málaga, Spain
| | - José M Jerez
- Computer Science Department, University of Málaga, Campus de Teatinos S/N, 29071 Málaga, Spain; Málaga Biomedical Research Institute (IBIMA), Málaga, Spain
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48
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Eng KH, Schiller E, Morrell K. On representing the prognostic value of continuous gene expression biomarkers with the restricted mean survival curve. Oncotarget 2016; 6:36308-18. [PMID: 26486086 PMCID: PMC4742179 DOI: 10.18632/oncotarget.6121] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 09/12/2015] [Indexed: 12/04/2022] Open
Abstract
Motivation Researchers developing biomarkers for cancer prognosis from quantitative gene expression data are often faced with an odd methodological discrepancy: while Cox's proportional hazards model, the appropriate and popular technique, produces a continuous and relative risk score, it is hard to cast the estimate in clear clinical terms like median months of survival and percent of patients affected. To produce a familiar Kaplan-Meier plot, researchers commonly make the decision to dichotomize a continuous (often unimodal and symmetric) score. It is well known in the statistical literature that this procedure induces significant bias. Results We illustrate the liabilities of common techniques for categorizing a risk score and discuss alternative approaches. We promote the use of the restricted mean survival (RMS) and the corresponding RMS curve that may be thought of as an analog to the best fit line from simple linear regression. Conclusions Continuous biomarker workflows should be modified to include the more rigorous statistical techniques and descriptive plots described in this article. All statistics discussed can be computed via standard functions in the Survival package of the R statistical programming language. Example R language code for the RMS curve is presented in the appendix.
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Affiliation(s)
- Kevin H Eng
- Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA
| | - Emily Schiller
- Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA
| | - Kayla Morrell
- Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA
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49
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Cardiac troponin T is an important predictor of mortality after cardiac surgery. J Crit Care 2016; 38:41-46. [PMID: 27837691 DOI: 10.1016/j.jcrc.2016.10.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 10/07/2016] [Accepted: 10/13/2016] [Indexed: 10/20/2022]
Abstract
PURPOSE Serum troponin (cTnT) levels, a commonly measured biomarker of myocardial injury, has rarely been considered in risk models after cardiac surgery. MATERIALS AND METHODS Retrospective study of patients undergoing any cardiac surgery between 2004 and 2012. Patients with a history of recent myocardial injury (<21 days) were excluded. The minimum P value approach was used to determine categories of peak cTnT associated with in-hospital death. A multivariable analysis was performed to identify independent predictors of mortality. RESULTS A total of 5318 patients without evidence of preoperative ischemia underwent a number of cardiac surgical interventions ranging from isolated coronary revascularization to combined valve coronary artery bypass grafting. The unadjusted in-hospital mortality rate was 3.3% (n = 175 patients). Four categories of peak cTnT were identified using the minimum P value approach: less than or equal to 0.6 ng/mL, 0.7 to 1.9 ng/mL, 2.0 to 3.1 ng/mL, and greater than 3.1 ng/mL with unadjusted mortality rates of 1.0%, 3.6%, 10.1%, and 33.1%, respectively. Multivariate logistic regression demonstrated that all peak cTnT levels greater than 0.6 ng/mL were independent predictors of in-hospital mortality in a dose-dependent manner. CONCLUSIONS We demonstrate that in patients without preoperative myocardial ischemia, the demonstration of myocardial injury (>0.6 ng/mL) in the postoperative period is highly predictive of in-hospital death.
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50
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Newschaffer CJ, Schriver E, Berrigan L, Landa R, Stone WL, Bishop S, Burkom D, Golden A, Ibanez L, Kuo A, Lakes KD, Messinger DS, Paterson S, Warren ZE. Development and validation of a streamlined autism case confirmation approach for use in epidemiologic risk factor research in prospective cohorts. Autism Res 2016; 10:485-501. [PMID: 27484054 DOI: 10.1002/aur.1659] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 05/20/2016] [Accepted: 06/02/2016] [Indexed: 11/07/2022]
Abstract
The cost associated with incorporating standardized observational assessments and diagnostic interviews in large-scale epidemiologic studies of autism spectrum disorders (ASD) risk factors can be substantial. Streamlined approaches for confirming ASD case status would benefit these studies. We conducted a multi-site, cross-sectional criterion validity study in a convenience sample of 382 three-year olds scheduled for neurodevelopmental evaluation. ASD case classification as determined by three novel assessment instruments (the Early Video-guided Autism Screener E-VAS; the Autism Symptom Interview, ASI; the Screening Tool for Autism in Toddlers Expanded, STAT-E) each designed to be administered in less than 30 minutes by lay staff, was compared to ADOS scores and DSM-based diagnostic assessment from a qualified clinician. Sensitivity and specificity of each instrument alone and in combination were estimated. Alternative cutpoints were identified under different criteria and two-stage cross validation was used to avoid overfitting. Findings were interpreted in the context of a large, prospective pregnancy cohort study utilizing a two-stage approach to case identification. Under initial cutpoints, sensitivity ranged from 0.63 to 0.92 and specificity from 0.35 to 0.70. Cutpoints giving equal weight to sensitivity and specificity resulted in sensitivity estimates ranging from 0.45 to 0.83 and specificity ranging from 0.49 to 0.86. Several strategies were well-suited for application as a second-stage case-confirmation. These included the STAT-E alone and the parallel administration of both the E-VAS and the ASI. Use of more streamlined methods of case-confirmation in large-scale prospective cohort epidemiologic investigations of ASD risk factors appears feasible. Autism Res 2017, 10: 485-501. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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Affiliation(s)
- Craig J Newschaffer
- A.J. Drexel Autism Institute, Drexel University, 3020 Market Street Suite 560, Philadelphia, PA, 19104
| | - Emily Schriver
- A.J. Drexel Autism Institute, Drexel University, 3020 Market Street Suite 560, Philadelphia, PA, 19104
| | - Lindsay Berrigan
- A.J. Drexel Autism Institute, Drexel University, 3020 Market Street Suite 560, Philadelphia, PA, 19104.,Center on Human Development and Disability, University of Washington, Box 357920, Seattle, WA, 98195-7920
| | - Rebecca Landa
- Center for Autism and Related Disorders, Kennedy Krieger Institute, 3901 Greenspring Avenue, Baltimore, MD, 21211
| | - Wendy L Stone
- Center on Human Development and Disability, University of Washington, Box 357920, Seattle, WA, 98195-7920
| | - Somer Bishop
- University of California San Francisco School of Medicine, 401 Parnassus Avenue, San Francisco, CA, 94143
| | - Diane Burkom
- Battelle Centers for Public Health Research and Evaluation, 6115 Falls Road, Baltimore, MD, 21209
| | - Anne Golden
- Ichan School of Medicine at Mount Sinai, 17 East 102 Street Floor 2nd Floor - West Tower Room D2-127, New York, NY, 10029
| | - Lisa Ibanez
- A.J. Drexel Autism Institute, Drexel University, 3020 Market Street Suite 560, Philadelphia, PA, 19104
| | - Alice Kuo
- University of California Los Angeles School of Medicine, UCLA Center for Health of Children, Families and Communities, 1100 Glendon Avenue, Suite 850, Los Angeles, CA, 90024
| | - Kimberly D Lakes
- University of California Irvine School of Medicine, 252 Irvine Hall, Irvine, CA, 92697
| | | | - Sarah Paterson
- The Center for Autism Research, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, 3535 Market Street, Suite 860, Philadelphia, PA, 19104.,Department of Psychology, Temple University, 1701 N. 13th Street, Philadelphia, PA, 19122
| | - Zachary E Warren
- Vanderbilt Kennedy Center Treatment and Research Institute for Autism Spectrum Disorders (TRIAD), Vanderbilt University, 110 Magnolia Circle, Nashville, TN, 37203
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