miR135a administration ameliorates brain ischemic damage by preventing TRPM7 activation during brain ischemia.

BACKGROUND: miRNA-based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity-independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. AIMS: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. METHODS: miR135a expression was evaluated by RT- PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. RESULTS: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. CONCLUSIONS: The early prevention of TRPM7 activation is protective during brain ischemia.

Contouring of emerging organs-at-risk (OARS) of the female pelvis and interobserver variability: A study by the Italian association of radiotherapy and clinical oncology (AIRO).

Purpose: To provide straightforward instructions for daily practice in delineating emerging organs-at-risk (OARs) of the female pelvis and to discuss the interobserver variability in a two-step multicenter study. Methods and materials: A contouring atlas with anatomical boundaries for each emerging OAR was realized by radiation oncologists and radiologists who are experts in pelvic imaging, as per their knowledge and clinical practice. These contours were identified as quality benchmarks for the analysis subsequently carried out. Radiation oncologists not involved in setting the custom-built contouring atlas and interested in the treatment of gynecological cancer were invited to participate in this 2-step trial. In the first step all participants were supplied with a selected clinical case of locally advanced cervical cancer and had to identify emerging OARs (Levator ani muscle; Puborectalis muscle; Internal anal sphincter; External anal sphincter; Bladder base and trigone; Bladder neck; Iliac Bone Marrow; Lower Pelvis Bone Marrow; Lumbosacral Bone Marrow) based on their own personal knowledge of pelvic anatomy and experience. The suggested OARs and the contouring process were then presented at a subsequent webinar meeting with a contouring laboratory. Finally, in the second step, after the webinar meeting, each participant who had joined the study but was not involved in setting the benchmark received the custom-built contouring atlas with anatomical boundaries and was requested to delineate again the OARs using the tool provided. The Dice Similarity Coefficient (DSC) and the Jaccard Similarity Coefficient (JSC) were used to evaluate the spatial overlap accuracy of the different volume delineations and compared with the benchmark; the Hausdorff distance (HD) and the mean distance to agreement (MDA) to explore the distance between contours. All the results were reported as sample mean and standard deviation (SD). Results: Fifteen radiation oncologists from different Institutions joined the study. The participants had a high agreement degree for pelvic bones sub-structures delineation according to DICE (IBM: 0.9 ± 0.02; LPBM: 0.91 ± 0.01). A moderate degree according to DICE was showed for ovaries (Right: 0.61 ± 0.16, Left: 0.72 ± 0.05), vagina (0.575 ± 0.13), bladder sub-structures (0.515 ± 0.08) and EAS (0.605 ± 0.05), whereas a low degree for the other sub-structures of the anal-rectal sphincter complex (LAM: 0.345 ± 0.07, PRM: 0.41 ± 0.10, and IAS: 0.4 ± 0.07). Conclusion: This study found a moderate to low level of agreement in the delineation of the female pelvis emerging OARs, with a high degree of variability among observers. The development of delineation tools should be encouraged to improve the routine contouring of these OARs and increase the quality and consistency of radiotherapy planning.

Validation of modular endoscopic medial maxillectomies for inverted papilloma of the maxillary sinus.

BACKGROUND: Treatment of inverted papilloma of the maxillary sinus (IPMS) has a lower success rate compared to other IPs. As such, its correct management generally needs trans-nasal endoscopic medial maxillectomy (EMMs) for adequate resection. The aim of this manuscript is to describe outcomes and major prognostic factors of a cohort of patients with IPMS who were treated with EMM. METHODOLOGY: In this multicentric study, patients affected with IPMS and treated with EMMs were included. The site of origin of the IPMS were studied as well as the type of EMM performed. The histological features (IP vs dysplasia), type of mucosal resection (total vs. pedicle oriented), and post-operative complications were analyzed. RESULTS: 310 patients were included (212 primary and 98 recurrent cases). After a mean follow-up of 45.4 months, 15 patients experienced recurrence (4.8%) due to the application of EMMs tailored to the surgical insertion point. Dysplasia was significantly associated with a higher risk of recurrence. The rates of early and late complications were 11.6% and 11.9%, respectively. CONCLUSIONS: IPMS resection via tailored EMM is associated with excellent disease control, thus excluding the systematic use of extended EMMs, which can however be justified in case of dysplastic IPMS given its significant impact on recurrence.

Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis.

To identify alternative interventions in neonatal hypoxic-ischemic encephalopathy, researchers' attention has been focused to the study of endogenous neuroprotective strategies. Based on the preconditioning concept that a subthreshold insult may protect from a subsequent harmful event, we aimed at identifying a new preconditioning protocol able to enhance Ca2+-dependent neurogenesis in a mouse model of neonatal hypoxia ischemia (HI). To this purpose, we also investigated the role of the preconditioning-linked protein controlling ionic homeostasis, Na+/Ca2+ exchanger (NCX). Hypoxic Preconditioning (HPC) was reproduced by exposing P7 mice to 20' hypoxia. HI was induced by isolating and cutting the right common carotid artery. A significant reduction in ischemic damage was observed in mice subjected to 20' hypoxia followed,3 days later, by 60' HI, thus suggesting that 20' hypoxia functions as preconditioning stimulus. HPC promoted neuroblasts proliferation in the dentate gyrus mirrored by an increase of NCX1 and NCX3-positive cells and an improvement of behavioral motor performances in HI mice. An attenuation of HPC neuroprotection as well as a reduction in the expression of neurogenesis markers, including p57 and NeuroD1, was observed in preconditioned mice lacking NCX1 or NCX3. In summary, PC in neonatal mice triggers a neurogenic process linked to ionic homeostasis maintenance, regulated by NCX1 and NCX3.

Postoperative radiotherapy after upfront radical prostatectomy: debated issues at a turning point-a survey exploring management trends on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology).

OBJECTIVES: Postoperative prostate cancer patients are a heterogeneous population, and many prognostic factors (e.g., local staging, PSA kinetics, margin status, histopathological features) may influence their clinical management. In this complex scenario, univocal recommendations are often lacking. For these reasons, the present survey was developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of Italian radiation oncologists and delineate a representation of current clinical practice in our country. METHODS: A questionnaire was administered online to AIRO (Italian Association of Radiotherapy and Clinical Oncology) members registered in 2020 with a clinical interest in uro-oncological disease. RESULTS: Sixty-one per cent of AIRO members answered the proposed survey. Explored topics included career and expertise, indications to adjuvant RT, additional imaging in biochemical recurrence setting, use of salvage radiotherapy (SRT), management of clinically evident locoregional recurrence and future considerations. CONCLUSIONS: Overall, good level of agreement was found between participants for most of the topics. Most debated issues regarded, as expected, implementation of new imaging methods in this setting. Notably, trend in favour of early SRT vs. immediate adjuvant RT was underlined, and preference for global evaluation rather than isolated risk factors for RT indications was noticed.

Acetic acid disinfection as a potential adjunctive therapy for non-severe COVID-19.

PURPOSE: SARS-CoV-2 is a new pandemic influenza caused by a coronavirus which main route of transmission is through exhaled droplets that primarily infect the nose and the nasopharynx. The aim of this paper is to evaluate the effect of acetic acid, the active component of vinegar, as a potential disinfectant agent for upper airways. METHODS: Twenty-nine patients were enrolled and divided into two groups: group 1 (14 patients) was composed of patients treated with off-label hydroxychloroquine and lopinavir/ritonavir, whereas group 2 (15 patients) was composed of patients treated with hydroxychloroquine only, combined with the inhalation of acetic acid disinfectant at a 0.34% concentration. A questionnaire-based evaluation of symptoms was performed after 15 days in both groups. RESULTS: It appears that the number of patients treated with acetic acid (group 2) that experienced improvement in individual symptoms was double that of the other group of patients (group 1), although numbers are too small for robust statistical analysis. CONCLUSIONS: Considering its potential benefits and high availability, acetic acid disinfection appears to be a promising adjunctive therapy in cases of non-severe COVID-19 and deserves further investigation.

Sodium/calcium exchanger as main effector of endogenous neuroprotection elicited by ischemic tolerance.

The ischemic tolerance (IT) paradigm represents a fundamental cell response to certain types or injury able to render an organ more "tolerant" to a subsequent, stronger, insult. During the 16th century, the toxicologist Paracelsus described for the first time the possibility that a noxious event might determine a state of tolerance. This finding was summarized in one of his most important mentions: "The dose makes the poison". In more recent years, ischemic tolerance in the brain was first described in 1991, when it was demonstrated by Kirino and collaborators that two minutes of subthreshold brain ischemia in gerbils produced tolerance against global brain ischemia. Based on the time in which the conditioning stimulus is applied, it is possible to define preconditioning, perconditioning and postconditioning, when the subthreshold insult is applied before, during or after the ischemic event, respectively. Furthermore, depending on the temporal delay from the ischemic event, two different modalities are distinguished: rapid or delayed preconditioning and postconditioning. Finally, the circumstance in which the conditioning stimulus is applied on an organ distant from the brain is referred as remote conditioning. Over the years the "conditioning" paradigm has been applied to several brain disorders and a number of molecular mechanisms taking part to these protective processes have been described. The mechanisms are usually classified in three distinct categories identified as triggers, mediators and effectors. As concerns the putative effectors, it has been hypothesized that brain cells appear to have the ability to adapt to hypoxia by reducing their energy demand through modulation of ion channels and transporters, which delays anoxic depolarization. The purpose of the present review is to summarize the role played by plasmamembrane proteins able to control ionic homeostasis in mediating protection elicited by brain conditioning, particular attention will be deserved to the role played by Na+/Ca2+ exchanger.

Palatal prosthetic rehabilitation in patients affected by cocaine-induced midline destructive lesions.

Cocaine is one of the most popular illicit drugs in Europe and cocaine-induced midline destructive lesions (CIMDL) represent a rare but destructive consequence of its intranasal use. The extent of lesions can vary remarkably and may include palate perforations with consequent oronasal reflux and hypernasal speech. The therapeutic options encompass surgery, with local and distant flaps, and prosthetic rehabilitation with palatal obturators. We retrospectively reviewed a case series of 6 patients affected by palatal perforation as part of CIMDL, who were treated with a dental or implant-retained palatal obturator at San Raffaele Dentistry Department between 2015 and 2020. In addition, we reviewed the available literature on CIMDL and the prosthetic rehabilitation of palatal perforations in this context. The most frequent symptoms reported were hypernasal speech, oro-nasal reflux, halitosis, and difficulty in interpersonal relationships. Palatal obturators were always successful in the relief of the majority of symptoms, but the duration of the benefit was strongly related to progression of the lesion, and in some cases a close follow-up and continuous modifications of the prosthesis were necessary. In conclusion prosthetic approach is a valid option for the symptomatic relief in CIMDL-related palate perforation. Nevertheless, the short-lasting efficacy for patients with active disease can be the reason for unsatisfactory results.

[Personality profiles of students at risk of dropping out: Resilients, Overcontrollers and Undercontrollers]. / Étudiants à risque de décrochage selon le profil de personnalité : Resilients, Overcontrollers et Undercontrollers.

INTRODUCTION: Preventing students from dropping out of higher education, and particularly university, requires understanding the different factors that can lead to individuals failing to complete their studies. The role of personality in academic success or failure remains poorly understood. Block's personality profile model (Resilients, Overcontrollers, Undercontrollers) has been used to link personality traits to academic performance. The objective of this study is to apply this model to the risk factors of dropping out of higher education courses, including psychological vulnerability, level of autonomy, and the feeling of not being able to keep up. This involved validating Block's profiles in relation to the Big Five personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism and Openness), and their links with the risk factors for dropping out. METHODS: This study is based on a quantitative survey of 196 students (mean age 21.32 years±3.11 years, with 63% females) taking higher education courses in France. Three measuring instruments were used: a French scale of Autonomy-situnomy, the French version of the Big Five Inventory (BFI-Fr) for personality traits, and the French version of the General Health Questionnaire (GHQ-28) for psychiatric morbidity. One item empirically evaluated the feeling of not being able to keep up. Data was processed using a k-average cluster analysis to establish the personality profiles, then by analysis of variance measures to evaluate the differences between them, and Bravais-Pearson correlation coefficient to identify links between risk factors and profiles. RESULTS: Conscientiousness (Control) was the trait most strongly associated with high autonomy and a low feeling of not being able to keep up. There was also a positive influence of Extraversion and Agreeableness on autonomy. On the other hand, Neuroticism scores were related to greater psychiatric morbidity, a greater feeling of not keeping up, and lower autonomy. The results for personality profiles confirm the stability of Block's profiles (Resilients, Overcontrollers and Undercontrollers) and their relevance in higher education contexts. Resilients and Overcontrollers had greater autonomy and a lower feeling of not keeping up, but Resilients had the lowest psychiatric morbidity. Undercontrollers were associated with the greatest risk factors: lowest autonomy, the highest psychiatric morbidity and the strongest feeling of not keeping up. Gender comparisons indicated that women were more affected by psychiatric morbidity, but had higher Conscientiousness and autonomy.

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/ß ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with (18)F-DPA-714 and micro-PET/CT.

PURPOSE: To evaluate the feasibility and sensitivity of (18)F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1(G93A) mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry. METHODS: Nine symptomatic SOD1(G93A) mice (aged 117 ± 12.7 days, clinical score range 1 - 4) and five WT SOD1 control mice (aged 108 ± 28.5 days) underwent (18)F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebellar (rCRB), brainstem (rBS), motor cortex (rMCX) and cervical spinal cord (rCSC) activities to that of the frontal association cortex. Two WT SOD1 and six symptomatic SOD1(G93A) mice were studied by immunohistochemistry. RESULTS: In the symptomatic SOD1(G93A) mice, rCRB, rBS and rCSC were increased as compared to the values in WT SOD1 mice, with a statistically significantly difference in rBS (2.340 ± 0.784 vs 1.576 ± 0.287, p = 0.014). Immunofluorescence studies showed that TSPO expression was increased in the trigeminal, facial, ambiguus and hypoglossal nuclei, as well as in the spinal cord, of symptomatic SOD1(G93A) mice and was colocalized with increased Iba1 staining. CONCLUSION: Increased (18)F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1(G93A) mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, (18)F-DPA-714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1(G93A) mouse model.

A case of Beckwith-Wiedemann syndrome with peculiar dental findings.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS, OMIM 130650) is a rare genetic disorder characterised by overgrowth, tumor predisposition and congenital malformations. Few systemic manifestations and oral features have been reported so far. CASE REPORT: We report on a case of BWS, describing all features expanding the knowledge on oro-dento-facial phenotypes, along with a review of the literature.

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype.

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in stroke and ischemic preconditioning and to propose, by modulating TRAIL pathway, a new therapeutic strategy in stroke. In order to achieve this aim a rat model of harmful focal ischemia, obtained by subjecting animals to 100 min of transient occlusion of middle cerebral artery followed by 24 h of reperfusion and a rat model of ischemic preconditioning in which the harmful ischemia was preceded by 30 mins of tMCAO, which represents the preconditioning protective stimulus, were used. Results show that the neuroprotection elicited by ischemic preconditioning occurs through both upregulation of TRAIL decoy receptors and downregulation of TRAIL itself and of its death receptors. As a counterproof, immunoneutralization of TRAIL in tMCAO animals resulted in significant restraint of tissue damage and in a marked functional recovery. Our data shed new light on the mechanisms that propagate ongoing neuronal damage after ischemia in the adult mammalian brain and provide new molecular targets for therapeutic intervention. Strategies aimed to repress the death-inducing ligands TRAIL, to antagonize the death receptors, or to activate the decoy receptors open new perspectives for the treatment of stroke.

Interobserver variability of clinical target volume delineation in soft-tissue sarcomas.

PURPOSE: The present observational study reports the results of a multi-institutional dummy-run designed to estimate the consistency of interobserver variability in clinical target volume delineation in two different cases of soft-tissue sarcomas in which postoperative and preoperative radiotherapy were prescribed, respectively. The purpose of this work was to quantify interobserver variability in routine clinical practice. PATIENTS AND METHODS: Two different cases of soft-tissues sarcomas were chosen: a case of postoperative and a case of preoperative radiation therapy. Participating centres were requested to delineate clinical target volumes according to their experience in both cases. Descriptive statistic was calculated for each variable (volume, diameters) separately for two cases. Box-whiskers plots were used for presentation of clinical target volume. A Shapiro-Wilk's test was performed to evaluate the departures from normality distribution for each variable. The comparison between relative variations of diameters was evaluated using the Student's t test. RESULTS: Several variations affecting both volumes and diameters were observed. Main variations were observed in the craniocaudal and laterolateral diameters. Each case showed similar dispersion, indicating a lack of reproducibility in volumes definition. CONCLUSIONS: This observational study highlighted that, in the absence of specific instructions or guidelines, the interobserver variability can be significant both in postoperative and preoperative radiotherapy of soft-tissue sarcomas.

Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results of a monoinstitutional prospective study.

PURPOSE: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in locally advanced rectal cancer (LARC) 8 weeks after neoadjuvant chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 28 patients with LARC underwent magnetic resonance imaging (MRI) prior to and 8 weeks after CRT. Tumor volume (TV) was calculated on T2-weighted MRI scans as well as the apparent diffusion coefficient (ADC) was calculated using Echo-planar DWI-sequences. All data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. Post-treatment difference ADC (%ΔADC) and TV (%ΔTV) changes at 8 weeks were compared complete response (CR; TRG1) and non-complete response tumors (non-CR; TRG2-5). RESULTS: The mean % ADC increase of CR group was significantly higher compared to non-CR group (77.2 ± 54.63% vs. 36.0 ± 29.44%; p = 0.05). Conversely, the mean % TV reduction did not significantly differ in CR group from non-CR group (73.7% vs. 63.77%; p = 0.21). Accordingly, the diagnostic accuracy of the mean % ADC increase to discriminate CR from non-CR group was significantly higher than that of the mean % TV reduction (0.913 vs. 0.658; p = 0.022). No correlation was found between mean % TV reduction and TRG (rho = 0.22; p = 0.3037), whereas a negative correlation between mean % ADC increase and TRG was recorded (r = -0.69; p = 0.006). CONCLUSION: The mean % ADC increase appears to be a reliable tool to differentiate CR from non-CR after CRT in patients with LARC.

Conjunctival instillation of plasminogen eliminates ocular lesion in B6.129P2-Plg(tm1Jld) transgenic mice, a model of ligneous conjunctivitis.

Ligneous conjunctivitis is a severe and rare chronic "idiopathic membraneous" conjunctivitis, characterized by the formation of pseudomembranes mostly on the palpebral surfaces that progressively replace the normal mucosa. Evidence has been provided that ligneous conjunctivitis is caused by a severe systemic plasminogen deficiency with decreased plasminogen antigen and decreased plasminogen functional activities. Objective of the present study is to verify the hypothesis that a topical eye application of plasminogen is able to ameliorate the consequences of this disease. Here we report the results of pre-clinical studies performed to investigate the therapeutic effectiveness of an eye-drop plasminogen preparation in B6.129P2-Plg(tm1Jld) transgenic mice, a model of ligneous conjunctivitis. The entity of protection mediated by plasminogen was evaluated by measuring the extent of the eye lesion by means of a computerized system and dedicated software. The results of the present study clearly showed that the administration for six times a day of plasminogen eye-drop solution in the lesioned eye of animals knock-out for plasminogen gene and developing ligneous conjunctivitis caused a dose and time related reduction of the extent of the ocular lesion. These findings may pave the road for the pharmacological treatment of the ocular lesion associated to the ligneous conjunctivitis that at the present is surgically treated by removing the pseudomembranes generated on the eye.

Tranexamic acid in primary CABG surgery: high vs low dose.

AIM: Prophylactic administration of tranexamic acid decreases bleeding and transfusions after cardiac procedures but it is still unclear what the best dose and the most appropriate timing to get the best results are. METHODS: We enrolled 250 patients scheduled for elective, primary coronary revascularization. They were randomly divided into 2 groups. Group H received tranexamic 30 mg x kg(-1) soon after the induction of anaesthesia and a further same dose was added to the prime solution of cardiopulmonary bypass (CPB). Group L received tranexamic acid 15 mg x kg(-1) after systemic heparinization followed by an infusion of 1 mg x kg(-1) h(-1) till the end of the operation. Transfusions of bank blood products, bleeding in the postoperative period and coagulation profile were recorded. RESULTS: We did not find any difference between the groups either with respect to transfusion requirements or with respect to blood loss. CONCLUSION: For elective, first time coronary artery bypass surgery, both dosages of tranexamic acid are equally effective. Theoretically, it seems safer to administer it when patients are protected from thrombus formation by full heparinization.