Browsing by Subject "Risk stratification"

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  • Koponen, Mikael; Havulinna, Aki S.; Marjamaa, Annukka; Tuiskula, Annukka M.; Salomaa, Veikko; Laitinen-Forsblom, Päivi J.; Piippo, Kirsi; Toivonen, Lauri; Kontula, Kimmo; Viitasalo, Matti; Swan, Heikki (2018)
    Background: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving beta-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. Methods: A follow-up study covering a mean of 18.6 +/- 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. Results: In mutation carriers, risk factors for cardiac events before initiation of beta-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p <0.001), a cardiac event before the age of 18 years (HR = 5.9, p <0.001), and QTc >= 500 ms (vs <470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0-3.9, p <0.001-0.03) compared to G589D, c. 1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c. 453delC, L552S and R176W mutations associated with lower risk (HR = 0.11-0.23, p <0.001) than other KCNH2 mutations. Conclusions: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.
  • Koponen, Mikael; Havulinna, Aki S; Marjamaa, Annukka; Tuiskula, Annukka M; Salomaa, Veikko; Laitinen-Forsblom, Päivi J; Piippo, Kirsi; Toivonen, Lauri; Kontula, Kimmo; Viitasalo, Matti; Swan, Heikki (BioMed Central, 2018)
    Abstract Background Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. Methods A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18–40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. Results In mutation carriers, risk factors for cardiac events before initiation of β-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p < 0.001), a cardiac event before the age of 18 years (HR = 5.9, p < 0.001), and QTc ≥500 ms (vs < 470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0–3.9, p < 0.001–0.03) compared to G589D, c.1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c.453delC, L552S and R176W mutations associated with lower risk (HR = 0.11–0.23, p < 0.001) than other KCNH2 mutations. Conclusions LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.
  • Huvila, Jutta; Laajala, Teemu D.; Edqvist, Per-Henrik; Mardinoglu, Adil; Talve, Lauri; Ponten, Fredrik; Grenman, Seija; Carpen, Olli; Aittokallio, Tero; Auranen, Annika (2018)
    Objective. In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods. A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results. A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (295%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P <0.001) of dying of EEC compared to the low-risk group. Conclusions. P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities. (C) 2018 Elsevier Inc. All rights reserved.
  • Tauriainen, Asta; Raitio, Arimatias; Tauriainen, Tuomas; Vanamo, Kari; Sankilampi, Ulla; Helenius, Ilkka; Hyvärinen, Anna (2022)
    Purpose The aim of the study was to compare and evaluate the utility of three different risk stratification scores for gastroschisis neonates; simple/complex gastroschisis, gastroschisis prognostic score and risk stratification index. Methods Data of neonates born with gastroschisis between the years 1993 and 2015 were collected. The national registers and patient records of four Finnish University Hospitals were retrospectively reviewed. Logistic and linear regression analysis were performed to identify independent predictors for adverse outcomes. The efficacy of these prognostic methods was further assessed using ROC-curves and DeLong (1988) test. Results Gastroschisis risk stratification index was an acceptable predictor of in-hospital mortality, AUC 0.70, 95% CI 0.48-0.91, p = 0.049. Complex gastroschisis and gastroschisis prognostic score were able to predict short bowel syndrome, AUC 0.80, 95% CI 0.58-1.00, p = 0.012 and AUC 0.80, 95% CI 0.59-1.00, p = 0.012, respectively. Conclusion There are three easily obtainable risk stratification scores for outcome prediction in gastroschisis patients, however, their predictive ability did not have a statistical difference in the present study. The Gastroschisis risk stratification index seemed to perform moderately well in mortality prediction.
  • Borssen, Magnus; Nordlund, Jessica; Haider, Zahra; Landfors, Mattias; Larsson, Par; Kanerva, Jukka; Schmiegelow, Kjeld; Flaegstad, Trond; Jonsson, Olafur Gisli; Frost, Britt-Marie; Palle, Josefine; Forestier, Erik; Heyman, Mats; Hultdin, Magnus; Lonnerholm, Gudmar; Degerman, Sofie (2018)
    Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients. Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data. Results: Among the 137 patients that later relapsed, patients with a CIMP-profile (n = 42) at initial diagnosis had an inferior overall survival (pOS(5years) 33%) compared to CIMP+ patients (n = 95, pOS(5years) 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors. Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.
  • Borssén, Magnus; Nordlund, Jessica; Haider, Zahra; Landfors, Mattias; Larsson, Pär; Kanerva, Jukka; Schmiegelow, Kjeld; Flaegstad, Trond; Jónsson, Ólafur G; Frost, Britt-Marie; Palle, Josefine; Forestier, Erik; Heyman, Mats; Hultdin, Magnus; Lönnerholm, Gudmar; Degerman, Sofie (BioMed Central, 2018)
    Abstract Background Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients. Methods Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1–18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data. Results Among the 137 patients that later relapsed, patients with a CIMP− profile (n = 42) at initial diagnosis had an inferior overall survival (pOS5years 33%) compared to CIMP+ patients (n = 95, pOS5years 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors. Conclusion CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.
  • HoT-PE Investigators; Barco, Stefano; Schmidtmann, Irene; Ageno, Walter; Harjola, Veli-Pekka; Lankeit, Mareike (2020)
    Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for >= 3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of alpha = 0.004 ( Conclusion Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.
  • ERN GUARD-HEART European Reference; Norrish, Gabrielle; Qu, Chen; Field, Ella; Ojala, Tiina H.; Kaski, Juan P. (2022)
    Aims Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort. Methods and results A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1-16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48-2.78]. Model validation showed a Harrell's C-index of 0.745 (95% CI 0.52-0.97) and Uno's C-index 0.714 (95% 0.58-0.85) with a calibration slope of 1.15 (95% 0.51-1.80). A 5-year predicted risk threshold of >= 6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60-0.81). Conclusions This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of >= 6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM.
  • Tolonen, Matti; Coccolini, Federico; Ansaloni, Luca; Sartelli, Massimo; Roberts, Derek J.; McKee, Jessica L.; Leppaniemi, Ari; Doig, Christopher J.; Catena, Fausto; Fabian, Timothy; Jenne, Craig N.; Chiara, Osvaldo; Kubes, Paul; Kluger, Yoram; Fraga, Gustavo P.; Pereira, Bruno M.; Diaz, Jose J.; Sugrue, Michael; Moore, Ernest E.; Ren, Jianan; Ball, Chad G.; Coimbra, Raul; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; McBeth, Paul B.; Posadas-Calleja, Juan G.; Di Saverio, Salomone; Xiao, Jimmy; Kirkpatrick, Andrew W. (2018)
    Background: Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. Methods: All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Results: Predictive systems with an area under-the-receiving-operating characteristic (AUQ curve >= 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score >= 2 (78.4%), followed by the WSESSSS score >= 8 (73.1%), SOFA >= 3 (752%), and APACHE II >= 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS >= 8 increased detection to 80%. Including CPIRO score >= 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA >= 4 and WSESSSS >= 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). Conclusions: No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest "inclusion-criteria" to recognize patients with a high chance of mortality and ICU admission.
  • Tolonen, Matti; Coccolini, Federico; Ansaloni, Luca; Sartelli, Massimo; Roberts, Derek J; McKee, Jessica L; Leppäniemi, Ari; Doig, Christopher J; Catena, Fausto; Fabian, Timothy; Jenne, Craig N; Chiara, Osvaldo; Kubes, Paul; Kluger, Yoram; Fraga, Gustavo P; Pereira, Bruno M; Diaz, Jose J; Sugrue, Michael; Moore, Ernest E; Ren, Jianan; Ball, Chad G; Coimbra, Raul; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; McBeth, Paul B; Posadas-Calleja, Juan G; Di Saverio, Salomone; Xiao, Jimmy; Kirkpatrick, Andrew W (BioMed Central, 2018)
    Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. Methods All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Results Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). Conclusions No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest “inclusion-criteria” to recognize patients with a high chance of mortality and ICU admission. Trial registration https://clinicaltrials.gov/ct2/show/NCT03163095 ; Registered on May 22, 2017.
  • Pasanen, Annukka; Loukovaara, Mikko; Tuomi, Taru; Butzow, Ralf (2017)
    Objective Preoperative or intraoperative risk assessment models are used to stratify patients with endometrial carcinoma to lymphadenectomy. Our aim was to determine whether preoperative analysis of L1 cell adhesion molecule (L1CAM) can improve risk assessment. Methods Immunohistochemical L1CAM staining was performed on endometrial biopsies of 241 patients and paired hysterectomy samples of 75 patients. Risk assessment models based on preoperative histologic type and grade, myometrial invasion, and/or tumor diameter and alternative models incorporating preoperative L1CAM were compared with regard to their capability of predicting lymph nodal or distant metastasis. Soluble L1 levels were measured by enzyme-linked immunosorbent assay in serum samples of 40 patients with endometrial carcinoma. Results The concordance rate between L1CAM staining results of preoperative and hysterectomy samples was moderate ( = 0.586, P <0.0001). Preoperative L1CAM expression was associated with nonendometrioid histology, lymph node involvement, advanced stage, and positive peritoneal cytology. Receiver operating characteristic curve analyses showed that L1CAM did not significantly improve risk stratification algorithms based on traditional risk factors. Intraoperative tumor diameter was an effective surrogate for myometrial invasion. There was no statistical difference between L1 serum levels of patients with an L1CAM-positive or L1CAM-negative endometrial carcinoma (P = 0.786). Conclusions L1 cell adhesion molecule expression in endometrial biopsy correlates with high-risk features of endometrial carcinoma but does not significantly improve risk stratification algorithms based on traditional factors. Soluble L1 detected in the serum of patients with endometrial carcinoma does not correlate with tumoral L1CAM expression.
  • Xu, Shishi; Coleman, Ruth L.; Wan, Qin; Gu, Yeqing; Meng, Ge; Song, Kun; Shi, Zumin; Xie, Qian; Tuomilehto, Jaakko; Holman, Rury R.; Niu, Kaijun; Tong, Nanwei (2022)
    Background People with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures. Methods A systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D. These Asian-derived and five prespecified non-Asian derived T2D risk prediction models were divided into BASIC (clinical variables only) and EXTENDED (plus laboratory variables) versions, with validation performed on them in three prospective Chinese IH cohorts: ACE (n = 3241), Luzhou (n = 1333), and TCLSIH (n = 1702). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test). Results Forty-four Asian and five non-Asian studies comprising 21 BASIC and 46 EXTENDED T2D risk prediction models for validation were identified. The majority were at high (n = 43, 87.8%) or unclear (n = 3, 6.1%) risk of bias, while only three studies (6.1%) were scored at low risk of bias. BASIC models showed poor-to-moderate discrimination with C-statistics 0.52-0.60, 0.50-0.59, and 0.50-0.64 in the ACE, Luzhou, and TCLSIH cohorts respectively. EXTENDED models showed poor-to-acceptable discrimination with C-statistics 0.54-0.73, 0.52-0.67, and 0.59-0.78 respectively. Fifteen BASIC and 40 EXTENDED models showed poor calibration (P < 0.05), overpredicting or underestimating the observed diabetes risk. Most recalibrated models showed improved calibration but modestly-to-severely overestimated diabetes risk in the three cohorts. The NAVIGATOR model showed the best discrimination in the three cohorts but had poor calibration (P < 0.05). Conclusions In Chinese people with IH, previously published BASIC models to predict T2D did not exhibit good discrimination or calibration. Several EXTENDED models performed better, but a robust Chinese T2D risk prediction tool in people with IH remains a major unmet need.
  • Ebner, Matthias; Pagel, Charlotta F.; Sentler, Carmen; Harjola, Veli-Pekka; Bueno, Hector; Lerchbaumer, Markus H.; Stangl, Karl; Pieske, Burkert; Hasenfuss, Gerd; Konstantinides, Stavros; Lankeit, Mareike (2021)
    Background: Arterial lactate is an established risk marker in patients with pulmonary embolism (PE). However, its clinical applicability is limited by the need of an arterial puncture. In contrast, venous lactate can easily be measured from blood samples obtained via routine peripheral venepuncture. Methods: We investigated the prognostic value of venous lactate with regard to in-hospital adverse outcomes and mortality in 419 consecutive PE patients enrolled in a single-center registry between 09/2008 and 09/2017. Results: An optimised venous lactate cut-off value of 3.3 mmol/l predicted both, in-hospital adverse outcome (OR 11.0 [95% CI 4.6?26.3]) and all-cause mortality (OR 3.8 [95%CI 1.3?11.3]). The established cut-off value for arterial lactate (2.0 mmol/l) and the upper limit of normal for venous lactate (2.3 mmol/l) had lower prognostic value for adverse outcomes (OR 3.6 [95% CI 1.5?8.7] and 5.7 [95% CI 2.4?13.6], respectively) and did not predict mortality. If added to the 2019 European Society of Cardiology (ESC) algorithm, venous lactate Conclusion: Venous lactate above the upper limit of normal was associated with increased risk for adverse outcomes and an optimised cut-off value of 3.3 mmol/l predicted adverse outcome and mortality. Adding venous lactate to the 2019 ESC algorithm may improve risk stratification. Importantly, the established cut-off value for arterial lactate has limited specificity in venous samples and should not be used.