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Objective: The present research was conducted to evaluate the negative effects of nicotine powder on the blood physiology, and biochemical and histological alterations of Labeo rohita. Materials and Methods: Fish were divided into four groups (1-4). Fish groups 2, 3, and 4 were exposed to different concentrations of nicotine, such as 0.75, 1.25, and 1.75 mg/l, while group 1 acted as a control. To find out the long-term impact of nicotine on body physiology, we conducted a 42-day experiment. After the completion of the experiment, hematology, biochemical assays, and histology were done. Results: Results revealed a considerable increase in HGB, red blood cells, WBCs, hematocrit, mean corpuscular volume, red cell distribution width -SD, procalcitonin, neutrophils, lymphocytes, monocytes, triglycerides, total cholesterol, low-density lipoprotein, very low-density lipoprotein, alanine transaminase, aspartate aminotransferase, globulin, thyroid stimulating hormone, BUN, creatinine, and blood glucose levels, whereas mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, RDW, platelet, high-density lipoprotein, albumin, total proteins, and T3 levels were significantly (p ≤ 0.05) decreased in exposed fish as compared to control group fish. Histological alterations showed that exposure to smokeless nicotine causes deleterious and degenerative effects in the liver, kidney, and gills of exposed fish. Conclusion: Nicotine administration in fish results in adverse effects on different biochemical and hematological parameters and causes histological alterations in some vital organs of exposed fish.
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Ewing sarcoma (ES) is an uncommon and highly aggressive bone malignancy that predominantly occurs in children and young adults. Extraosseous Ewing sarcoma (EES), an even rarer variant, can present in the soft tissues instead of bone. In this case report, we detail a previously healthy 28-year-old male presenting with an isolated enlarged left inguinal lymph node, subsequently diagnosed as EES. The patient presented with a three-month history of a non-tender, gradually enlarging lump in the left groin. Fine needle aspiration revealed a small round blue cell tumor with a high Ki-67 score, and subsequent excisional biopsy identified a rare genetic fusion mutation. Postoperative positron emission tomography (PET)/computed tomography (CT) scan did not show any fludeoxyglucose F18 (FDG) uptake lesions to suggest residual malignancy. The patient is currently awaiting chemotherapy. Throughout the discussion of this case, we highlight the importance of considering EES in the differential diagnosis of isolated lymph node enlargement, the role of genetic testing in diagnosis, and the treatment modalities offered.
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Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from 2 phase 3, single-arm studies. Setting & Participants: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure: Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy - Fatigue score achieved by 26 weeks was maintained over 2 years. Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS.
This research tested a drug called ravulizumab for the treatment of atypical hemolytic uremic syndrome (aHUS). aHUS is a rare disease that causes clots in tiny blood vessels. This can damage the kidneys and other organs. We analyzed data from 2 clinical trials in which children and adults with aHUS received ravulizumab through a tube placed in a vein (intravenous line). They received ravulizumab every 4-8 weeks depending on their weight. We found that treating patients for 2 years with ravulizumab was associated with improved blood health, kidney function, and quality of life and was well tolerated. These results support ravulizumab as a long-term treatment for people with aHUS.
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A five-year-old boy presented with bilateral acute proptosis, papilledema, and sub-retinal fluid. Notably, choroidal thickening exceeded 600 microns. These ocular findings were the initial manifestations of acute lymphoblastic leukemia. This case underscores the importance of recognizing uncommon ocular presentations in pediatric leukemia for timely diagnosis and management.
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OBJECTIVE: To determine the pharmaceutical interventions in patients eligible for phase I cancer clinical trials, focusing specifically on exclusion criteria related to medication or relevant interactions. METHOD: Descriptive, observational study conducted at a comprehensive cancer centre. Patients undergoing screening for phase I clinical trials (March 2019-December 2022) were included. The pharmacist reviewed concomitant medication and provided a recommendation. RESULTS: The concomitant medication of 512 patients eligible to participate in 84 phase I clinical trials was analysed. In 230 (44.9%) patients, the clinical trial treatment included oral medication. The median number of concomitant medications was 5 (IQR 3-8) per patient.A total of 280 pharmaceutical interventions were performed in 140 (27.3%) patients: 240 (85.7%) were due to interactions in 124 (24.2%) patients, and 40 (14.3%) were due to exclusion criteria in 34 (6.6%) patients. Interactions and exclusion criteria were detected in 18 (3.5%) patients. The main groups of drugs involved were 68 (24.3%) antacids and antiulcer drugs, 28 (10.0%) antidepressants and 26 (9.3%) opioids. Acceptance analysis of the recommendation was applicable in 215 cases; in 208 (96.7%), the pharmaceutical intervention was accepted.Differences were identified for exclusion criteria (7 vs 27) and interactions (37 vs 87) between parenteral and oral clinical trial medication (p<0.001). CONCLUSION: The pharmacist's review of concomitant medication during the screening period in phase I clinical trials enables the detection of prohibited medication or relevant interactions, potentially avoiding screening failures and increasing the efficacy and safety of treatments.
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The development of hematology in China has gradually begun since the 1950s. After several generations of hard work, it has grown into a young but vibrant discipline. The development of Chinese hematology has experienced rapid rise and steady growth, but there is still a gap with the international level of hematology development. Only by constructing a Chinese community of hematology and forming a joint force to promote the development of hematology can we better realize the Chinese Dream in the field of hematology.
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Hematology , China , Humans , East Asian PeopleABSTRACT
The literature widely supports the benefits of early integration of palliative care into pediatric oncological care; however, many barriers to its successful integration remain. Integrating palliative care as early as possible in the oncology pathway is critical, but other criteria are relevant to positive results. This paper aims to contribute to the early/late referral dualism in pediatric palliative care (PPC) and highlight the importance of a collaborative approach between oncologists and palliative care teams. This study investigates the impact of early versus late referral to PPC, intersecting it with the synergy work between services and the related outcomes. The four pediatric cancer cases were selected based on clinical (e.g., disease duration, multiple treatments, and pain management), management (e.g., involvement of multiple services and multiple home-hospital transitions), and relevance of multidisciplinary team (e.g., difficult clinical decisions and ethical discussions) criteria. A mixed-methods approach was employed, combining qualitative case analysis using clinical diaries, literature review, and practice guidelines development. Critical clinical information, time course, clinician-family communication, and patient involvement were analyzed. The outcomes show how simultaneous care creates continuous discussion and dialogue between professionals. The results indicate the importance of better communication and care coordination to improve patient and family satisfaction, highlighting the uniqueness of the pediatric field and the relationship with children and families. Through the discussion of clinical cases and a literature review, we provide practical guidance for clinicians working in oncology and PPC. These findings underscore the crucial need for a multidisciplinary approach in pediatric oncology, advocating policy changes to support early PPC integration and translate it into complementarity best operating practices. In conclusion, besides assessing the timeliness of referral to the PPC service, the synergy, harmony, and choral work of the professionals involved are equally valuable for a quality-of-life-oriented care plan.
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BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriacea (ESBL-E) infections are a major source of mortality and morbidity in patients with hematologic cancers. One of the most significant risk factors for bacterial illness is prior colonization with resistant germs. Empiric usage of carbapenems is recommended for the treatment of infections in patients with a positive colonization history. OBJECTIVES: We aimed to determine the outcome of empirical carbapenem (de-escalation) versus non-carbapenem (escalation) therapy in adult hematology patients who have rectal extended-spectrum beta-lactamase positive ESBL-E colonization. METHODS: Two hundred three rectal swab cultures were collected from 130 patients, admission or during hospitalization between June 2014 and May 2015. Patients were followed till January 2016 for future infections due to ESBL-E. Empirical antibiotic treatment was started according to the patient's medical condition without consideration of previous colonization status. Stable patients received empirical escalation therapy. All-cause and early mortality of infections are analyzed. RESULTS: Seventy-three (36%) swabs were positive for ESBL-E. Patients with rectal ESBL-E colonization were defined as cases; patients without colonization were defined as controls. Prospective infection due to ESBL-E in the case and control group was 6.8% and 2.3%, respectively. No statistically significant relation was found between colonization and prospective infection due to ESBL-E (p=0.110). There was no all-cause or early mortality in prospective infections with ESBL-E. Among case patients, one patient each died from all-cause mortality in the escalation (n=55) and de-escalation (n=3) group. The all-cause mortality in the antibiotic switch group (n=30) was eight, including five patients in the early mortality group although the bacteriologic agents were susceptible to the given antibiotics. CONCLUSION: In our institution, rectal colonization with ESBL-E was high, but contracting an infection due to ESBL-E was surprisingly low. Colonization with ESBL-E may not necessarily end with an infection in some situations. In stable patients, disregarding colonization features before empirical therapy did not seem to be inappropriate.
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Multiple myeloma (MM) is one of the world's most recognized bone marrow (BM) cancers. It is considered a plasma cell dyscrasia in which normal plasma cells transform into malignant cells that produce large quantities of an abnormal immunoglobulin called monoclonal protein better known as M protein. This, in turn, is responsible for many of its bone and kidney-related manifestations. Many translocations are associated with the disease, such as t(11;14), t(4;14), and t(14;16). Of these, the most common is t(11;14). In this subset of MM, there is a specific genetic alteration affecting the CCND1 gene. Typically inactive in plasma cells, this gene, when disrupted, promotes uncontrolled cell proliferation. Simultaneously, there is a reduction in CD38 levels, a protein typically elevated in MM patients. This combination of genetic and protein expression is a defining feature of this subgroup within the MM spectrum. In this report, we present a case of a 75-year-old male who was referred by an oncologist for comprehensive diagnostic testing. He was found to have significant hyperploidy involving trisomy 9 and an extra copy of CCND1 with concomitant trisomy 11q confirming a t(11;14) translocation. Further workup involving cytology revealed that the patient also expressed elevated levels of CD38, which, given this mutation, would be expected to be low in this patient population. We aim to highlight the importance and prognostic value of this mutation and further add to the already growing body of literature associated with this disease.
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Diamond-Blackfan anemia syndrome (DBA) is a ribosomopathy associated with loss-of-function variants in more than 20 ribosomal protein (RP) genes. Here, we report the genetic, functional and biochemical dissection of two multigenerational pedigrees with variants in RPL17, a large ribosomal subunit protein-encoding gene. Affected individuals had clinical features and erythroid proliferation defects consistent with DBA. Furthermore, RPL17/uL22 depletion resulted in anemia and micrognathia in zebrafish larvae, and in vivo complementation studies indicated that RPL17 variants were pathogenic. Lymphoblastoid cell lines (LCLs) derived from patients displayed a ribosomal RNA maturation defect reflecting haploinsufficiency of RPL17. The proteins encoded by RPL17 variants were not incorporated into ribosomes, but 10-20% of 60S ribosomal subunits contained a short form of 5.8S rRNA (5.8SC), a species that is marginal in normal cells. These atypical 60S subunits were actively engaged in translation. Ribosome profiling showed changes of the translational profile, but those are similar to LCLs bearing RPS19 variants. These results link an additional RP gene to DBA. They show that ribosomes can be modified substantially by RPL17 haploinsufficiency, but support the paradigm that translation alterations in DBA are primarily related to insufficient ribosome production rather than to changes in ribosome structure or composition.
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INTRODUCTION: Laboratories use their performance in external quality assurance (EQA) to establish quality planning strategies and to assess whether testing processes require improvement. METHODS: The EQA performance of the hematology and coagulation test parameters on the Royal College of Pathologists of Australasia EQA program was evaluated over a 4-year cycle at an academic hospital in Johannesburg, South Africa. The test performance was determined from analytical quality specification (APS) and/or z-scores. Bias and imprecision were used to calculate sigma (σ) metric scores. Specifications from European Federation of Laboratory Medicine and/or biological variation were applied. RESULTS: The laboratory achieved a mean testing score of 98.7 ± 4.0%. There were 103 (10.7%) unacceptable results. On investigation, root causes included: presurvey issues (83%), transcription errors (9%), random errors (6%), and test performance errors (3%). All test parameters evaluated achieved an acceptable median APS during the study period. The mean z-scores, however, were >2 and unacceptable for mean cell hemoglobin concentration and hematocrit. On investigation, this was attributed to significant delay in transport and storage of full blood count samples. White cell count and d-dimer achieved a σ ≥ 6. CONCLUSION: EQA participation assisted the laboratory in maintaining a quality system. Close monitoring is necessary for international laboratories to avoid sample delays that can affect result quality.
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Background: COVID-19 is still a global health issue, there is limited evidence in South America regarding laboratory biomarkers associated with severe disease. The objective of our study was to identify hematological and hemostatic changes associated with severe COVID-19. Methods: A total of 170 hospitalized patients with COVID19 were included in the study, defining their severity according to established criteria. Demographic, clinical, and laboratory (days 1, 3, 7, 15) data were obtained. We performed a statistical analysis, assuming significance with a value of p < 0.05. We analyzed the correlation between severity and biomarkers and established cut-off values for severe patients through ROC curves, estimating Odds Ratio associated with severe disease. Results: Day 1 was observed significant differences between moderate vs severe patients for leukocytes (WBC), Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and D-dimer, establishing cut-off points for each of them. The markers we found associated to risk of severe disease were WBC (OR=3.2396; p = 0.0003), NLR (OR=5.7084; p < 0.0001), PLR (OR=4.4094; p < 0.0001), Neutrophil (OR=4.1193; p < 0.0001), D-dimer (OR=2.7827; p = 0.0124). Conclusions: The results allow to establish basic laboratory biomarkers associated to severe disease, which could be used as prognostic markers.
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INTRODUCTION: We aimed to develop an automated, low-volume method for thrombocyte counting in capillary blood using the Sysmex predilution (PD) mode. METHODS: Microsamples were prepared by resuspension of 50 µL blood in 300 µL DCL CellPack. Thrombocyte counting was done in the impedance (PLT-I) and fluorescence (PLT-F) channels. The imprecision and bias was evaluated in >394 microsamples from adult blood. Preanalytical factors (skin-piercing, storage, and transportation in our pneumatic tube system) was assessed, and studies on pediatric microsamples were made for comparison. The improvement in analytical quality and turnaround time was examined. RESULTS: For PLT-F, the imprecision was 1.1%-3.7%, and the bias was 10.1% (95% CI: 8.8-11.3). After skin-piercing, the bias was 8.1% (95% CI: 5.6-10.6) and the imprecision 1.9% (95% CI: 1.3-2.5). Thrombocyte counts kept stable after 4 h at room temperature (94.8% [95% CI: 93.2-96.4]) and after pneumatic tube transportation [6.7% (95% CI: 4.8-8.6)]. The bias of the PD mode for pediatric microsamples was 13.0% (95% CI: -8.4-34.4) in the PLT-F channel. The automated method had a considerably lower imprecision than the existing manual thrombocyte counting method and reduced turnaround times. CONCLUSION: The automated microsample method offers a low-volume alternative for measurement of thrombocytes. The method appears useful also in pediatric samples.
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Background/Objectives: Many patients suffering from liver cirrhosis are eventually added to waiting lists for liver transplantation whose priority is established based on scales such as the Child-Pugh score. However, two marker rhythms of the circadian system, motor activity and distal temperature, are not evaluated. Methods: To determine the relationship between the functional status of the circadian system and the Child-Pugh scale in patients awaiting liver transplantation, distal temperature, motor activity, and light exposure rhythms were monitored for a full week using a wrist device (Kronowise 6.0) in 63 patients (17 women, 46 men) aged between 20 and 76 years. Results: Circadian parameters (amplitude, regularity, and fragmentation) of motor activity rhythms, distal temperature, and light exposure worsen in close association with liver disease severity as assessed by using the Child-Pugh score. Likewise, the worsening of rhythmic parameters and liver disease is associated with a deterioration in the markers of the red series: count, hemoglobin, and hematocrit. Conclusions: These results indicate the utility of ambulatory monitoring of marker rhythms to complement the clinical information provided by the Child-Pugh scale and to help establish nutrition, physical exercise, and sleep guidelines that promote better survival and quality of life in these patients.
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BACKGROUND: The cellular and molecular changes during red blood cell (RBC) storage that affect posttransfusion recovery (PTR) remain incompletely understood. We have previously reported that RBCs of different storage biology cross-regulate each other when stored together (co-storage cross-regulation [CSCR]). However, the mechanism of CSCR is unclear. In the current study, we tested the hypothesis that CSCR involves acquisition of molecular signatures associated with PTR. STUDY DESIGN AND METHODS: The whole blood compartment of either B6 or FVB mice was biotinylated in vivo prior to blood collection and storage. Bio-B6 or Bio.FVB were stored with RBCs from B6 mice transgenic for green florescent protein (GFP) (B6.GFP). After storage, avidin-magnetic beads were used to simultaneous purify Bio-RBCs (positive selection) and B6.GFPs (negative selection). Isolated populations were analyzed by transfusion to establish PTR, and subjected to metabolomic and proteomic analysis. RESULTS: B6 RBCs acquired molecular signatures associated with stored FVB RBCs at both the metabolomic and proteomic level including metabolites associated with energy metabolism, oxidative stress regulation, and oxidative damage. Mitochondrial signatures were also acquired by B6 RBCs. Protein signatures acquired by B6 RBCs include proteins associated with vesiculation. CONCLUSION: The data presented herein demonstrate the appearance of multiple molecular changes from poor-storing RBCs in good-storing RBCs during co-storage. Whether this is a result of damage causing intrinsic molecular changes in B6 RBCs or if molecules of FVB RBC origin are transferred to B6 RBCs remains unclear. These studies broaden our mechanistic understanding of RBC storage (in particular) and potentially RBC biology (in general).
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The evolution of complete blood count (CBC) methodology from manual calculations to sophisticated high throughput hematology analyzers is the focus of this article. In recent years, hematology testing has greatly benefitted from the combination of various technologies with automated neural networks. In addition to an increasing complexity of the laboratory instrumentation, there is a demand on point of care CBC testing with its benefits and drawbacks. This article highlights exciting advancements of hematology testing from the past to the present and into the future.
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Hematology , Humans , Blood Cell Count/instrumentation , Hematology/instrumentation , Hematology/trends , Hematologic Tests/instrumentation , Hematologic Tests/trends , Neural Networks, ComputerABSTRACT
This article provides a comprehensive overview of Heparin-Induced Thrombocytopenia (HIT) with an emphasis on laboratory testing and advantages of automation. HIT is a critical condition arising from heparin exposure, leading to a contradictory combination of thrombocytopenia with an increased thrombosis risk. The article discusses HIT's history, clinical presentation, laboratory diagnosis, and management strategies. It highlights the importance of interdisciplinary collaboration for effective diagnosis and treatment, underscoring advancements in technology and targeted therapies that are shaping future approaches to HIT management.
Subject(s)
Anticoagulants , Heparin , Thrombocytopenia , Humans , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Heparin/adverse effects , Anticoagulants/adverse effectsABSTRACT
The etiology of vascular problems in beta-thalassemia has been linked to endothelial damage. Antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFLT-1) inhibit the signaling of vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), resulting in a decrease in the development of new blood vessels. Additionally, they promote the maturation of existing blood vessels and lead to endothelial dysfunction. This study aimed to assess the role of sFLT-1 in adult patients with beta-thalassemia major (TM) as a biomarker of endothelial dysfunction and its association with pulmonary hypertension (PHT). A total of 90 subjects were recruited and categorized into two groups: 45 patients with beta-TM, who were further divided based on the presence or absence of PHT, and 45 healthy individuals served as a control group. Serum sFLT-1 was determined using the enzyme-linked immunosorbent assay (ELISA) technique. The results revealed that Beta-TM patients had higher sFLT-1 levels than the control group. In addition, patients with PHT had significantly higher sFLT-1 levels compared to those without PHT. The levels of sFLT-1 were positively correlated with von Willebrand factor (vWF), serum ferritin, and high-sensitivity C-reactive protein (hs-CRP). Regression analyses demonstrated a significant association between high sFLT-1 levels and the occurrence of PHT. Additionally, sFLT-1 (at a cutoff value of 8.84 pg/ml) demonstrated a sensitivity of 83.30% and specificity of 80.0% in diagnosing thalassemic patients with PHT. In conclusion, beta-TM patients with elevated serum levels of sFLT-1 are at risk of developing endothelial dysfunction and subsequent development of PHT.
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INTRODUCTION: The platelet fluorescent counting (PLT-F) method is utilized as a reflex test method following the initial test of the platelet impedance counting (PLT-I) method in clinical practice on the Sysmex XN-series automated hematology analyzer. Our aim is to establish reflex test rules for the PLT-F method by combining multiple parameters provided by the "CBC + DIFF" mode of the Sysmex XN-series automated hematology analyzer. METHODS: We tested 120 samples to evaluate the baseline bias between the PLT-F and PLT-I methods. Then, we selected 1256 samples to establish and test reflex test rules using seven machine learning models (decision Tree, random forest, neural network, logistic regression, k-nearest neighbor, support vector machine, and Naive Bayes). The training set and test set were divided at a ratio of 7:3. We evaluated the performance of machine learning models on the test set using various metrics to select the most valuable model. RESULTS: The PLT-F method exhibited a high degree of correlation with the PLT-I method (r = 0.998). The random forest model emerged as the most valuable, boasting an accuracy of 0.893, an area under the curve of 0.954, an F1 score of 0.771, a recall of 0.719, a precision of 0.831, and a specificity of 0.950. The most important variable in the random forest model was mean cell volume, weighted at 15.09%. CONCLUSION: The random forest model, which demonstrated high efficiency in our study, can be used to establish PLT reflex test rules based on the PLT-F method for the Sysmex XN-series automated hematology analyzer.
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Cryptococcus is an opportunistic fungal pathogen that can cause disseminated infection with predominant central nervous system involvement in patients with compromised immunity. Biologics are increasingly used in the treatment of neoplasms and autoimmune/inflammatory conditions and the prevention of transplant rejection, which may affect human defense mechanisms against cryptococcosis. In this review, we comprehensively investigate the association between cryptococcosis and various biologics, highlighting their risks of infection, clinical manifestations, and clinical outcomes. Clinicians should remain vigilant for the risk of cryptococcosis in patients receiving biologics that affect the Th1/macrophage activation pathways, such as tumor necrosis factor α antagonists, Bruton tyrosine kinase inhibitors, fingolimod, JAK/STAT inhibitors (Janus kinase/signal transducer and activator of transcription), and monoclonal antibody against CD52. Other risk factors-such as age, underlying condition, and concurrent immunosuppressants, especially corticosteroids-should also be taken into account during risk stratification.