Diagnostic performance of mobile cone beam computed tomography versus conventional multi-detector computed tomography in orbital floor fractures: a study on human specimens.

The aim of this study was to evaluate the diagnostic accuracy of mobile cone beam computed tomography (MCBCT) versus multi-detector computed tomography (MDCT) in orbital floor fractures. Twenty-four fresh cadaver heads were used, and one orbital floor was fractured for each head by transconjunctival approach. MDCT and MCBCT were performed on each of the heads. The images obtained were then analysed independently by eight evaluators. The radiological characteristics of the orbital floor fractures were visualized with good interpretation agreement between the two images. The location of the fracture and enophthalmos were identified in a comparable manner with strong agreement (κ=0.93 and κ=0.85, respectively). Measurements of fatty hernias and bone defects showed a strong correlation between the two imaging modalities (Pearson coefficient between 0.64 and 0.71 and between 0.67 and 0.71, respectively). The fracture limits and the presence of bone fragments, an intrasinus fatty hernia, and a fracture of the associated medial orbital wall were visualized in both examinations with good agreement (κ=0.68, κ=0.51, κ=0.57, and κ=0.46, respectively). The soft tissue study showed superiority for MDCT, with a κ<0.0009. MCBCT showed good diagnostic performance in the study of orbital floor fracture characteristics.

How useful is intraoperative cone beam computed tomography in maxillofacial surgery? An overview of the current literature.

Intraoperative imaging is increasingly used by surgeons and has become an integral part of many surgical procedures. This study was performed to provide an overview of the current literature on the intraoperative use of cone beam computed tomography (CBCT) imaging in maxillofacial surgery. A bibliographic search of PubMed was conducted in March 2020, without time limitation, using "intraoperative imaging" AND "maxillofacial surgery" AND "cone beam computed tomography" as key words. Ninety-one articles were found; after complete reading, 16 articles met the eligibility criteria and were analysed. The results showed that the majority of the indications were related to maxillofacial trauma, particularly zygomaticomaxillary complex fractures. Final verification with intraoperative CBCT before wound closure was the most common use of this device. However, innovative uses of intraoperative CBCT are expanding, such as CBCT coupling with mirror computational planning, and even the combined use of initial intraoperative CBCT acquisition with navigation. Immediate, fast, and easy evaluation of bone repositioning to avoid the need for further surgical revision is the main advantage of this technique. Imaging quality is comparable to that of multi-slice computed tomography, but with lower radiation exposure. Nevertheless, CBCT is still not widely available in maxillofacial centres, probably because of its cost, and perhaps because not everyone is aware of its advantages and versatility, which are reported in this review.

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory.

Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.

The high sub-mandibular approach: Our experience about 496 procedures.

INTRODUCTION: The potential drawbacks of surgical approaches to neck and base fractures of the mandibular condyle (visible scare, facial nerve injury) are still considered by many surgeons as a brake for open reduction and internal fixation. The aim of our study was to analyze the results in terms of access, scare quality and complications that could be noticed in a 12 years period of time with the use of the high sub-mandibular approach (HSMA) we first described in 2006 for the surgical treatment of neck and base fractures. MATERIAL AND METHOD: All the files of patients operated on for condylar neck and base fractures approached by mean of a HSMA between January 2006 and December 2018 in our department and containing information concerning age, sex, type of fracture, kind of osteosynthesis material, operating time, name of the surgeon, postoperative complication linked to the approach, scare quality at 6 months follow-up at least were included. The skin incision and the dissection planes followed the original publication of Meyer et al. in 2006. RESULTS: 434 patients (sex ratio: 2.06, mean age: 32, 496 approaches) met the inclusion criteria. Following the AO classification, 21.2% of the fractures were classified as neck fractures and 78.8% as base fractures. 97.6% of all fractures were stabilized by mean of a 3D plate (TCP® plate, Medartis, Basel-CH), the remaining ones by mean of a combination of 1.2, 1.5 and 2.0 straight plates. Mean operating time was 40minutes per side. Patients were operated on by senior surgeons in 71.7% of the cases and by trainees under supervision for the others. Concerning the complications linked to the approach, we noticed 11 (2.2%) temporary (0 definitive) paresis of the facial nerve, 1 (0.2%) hematoma and 1 (0.2%) abscess that both needed revision. Scare was hypertrophic or considered as unaesthetic by the patient in 5 cases (1%). DISCUSSION: The HSMA, if performed as initially described, is a safe and quick procedure compared to other cutaneous approaches. It gives access to all base fractures and to most of neck fractures. The very low rate of facial nerve complications is mainly explained by the plane by plane dissection making it very easy to avoid the facial nerve branches or to check them when encountered. The HSMA is particularly suited to the use of TCP plates as the upper holes of these plates, placed horizontally, are easy to reach from below. The HSMA is therefore still our preferred cutaneous approach to the condylar process.

Implementation of a classification strategy of Raman data collected in different clinical conditions: application to the diagnosis of chronic lymphocytic leukemia.

The literature is rich in proof of concept studies demonstrating the potential of Raman spectroscopy for disease diagnosis. However, few studies are conducted in a clinical context to demonstrate its applicability in current clinical practice and workflow. Indeed, this translational research remains far from the patient's bedside for several reasons. First, samples are often cultured cell lines. Second, they are prepared on non-standard substrates for clinical routine. Third, a unique supervised classification model is usually constructed using inadequate cross-validation strategy. Finally, the implemented models maximize classification accuracy without taking into account the clinician's needs. In this paper, we address these issues through a diagnosis problem in real clinical conditions, i.e., the diagnosis of chronic lymphocytic leukemia from fresh unstained blood smears spread on glass slides. From Raman data acquired in different experimental conditions, a repeated double cross-validation strategy was combined with different cross-validation approaches, a consensus label strategy and adaptive thresholds able to adapt to the clinician's needs. Combined with validation at the patient level, classification results were improved compared to traditional strategies.

How useful is 3D printing in maxillofacial surgery?

INTRODUCTION: 3D printing seems to have more and more applications in maxillofacial surgery (MFS), particularly since the release on the market of general use 3D printers several years ago. The aim of our study was to answer 4 questions: 1. Who uses 3D printing in MFS and is it routine or not? 2. What are the main clinical indications for 3D printing in MFS and what are the kinds of objects that are used? 3. Are these objects printed by an official medical device (MD) manufacturer or made directly within the department or the lab? 4. What are the advantages and drawbacks? METHODOLOGY: Two bibliographic researches were conducted on January the 1st, 2017 in PubMed, without time limitation, using "maxillofacial surgery" AND "3D printing" for the first and for the second "maxillofacial surgery" AND "computer-aided design" AND "computer-aided manufacturing" as keywords. Articles in English or French dealing with human clinical use of 3D printing were selected. Publication date, nationality of the authors, number of patients treated, clinical indication(s), type of printed object(s), type of printing (lab/hospital-made or professional/industry) and advantages/drawbacks were recorded. RESULTS: Two hundred and ninety-seven articles from 35 countries met the criteria. The most represented country was the People's Republic of China (16% of the articles). A total of 2889 patients (10 per article on average) benefited from 3D printed objects. The most frequent clinical indications were dental implant surgery and mandibular reconstruction. The most frequently printed objects were surgical guides and anatomic models. Forty-five percent of the prints were professional. The main advantages were improvement in precision and reduction of surgical time. The main disadvantages were the cost of the objects and the manufacturing period when printed by the industry. DISCUSSION: The arrival on the market of low-cost printers has increased the use of 3D printing in MFS. Anatomic models are not considered to be MDs and do not have to follow any regulation. Nowadays, they are easily printed with low-cost printers. They allow for better preoperative planning and training for the procedures and for pre-shaping of plates. Occlusal splints and surgical guides are intended for the smooth transfer of planning to the operating room. They are considered to be MDs and even if they are easy to print, they have to follow the regulations applying to MDs. Patient specific implants (custom-made plates and skeletal reconstruction modules) are much more demanding objects and their manufacturing remains nowadays in the hands of the industry. The main limitation of in-hospital 3D printing is the restrictive regulations applying to MDs. The main limitations of professional 3D printing are the cost and the lead time. 3D printed objects are nowadays easily available in MFS. However, they will never replace a surgeon's skill and should only be considered as useful tools.

Influence of apixaban on commonly used coagulation assays: results from the Belgian national External Quality Assessment Scheme.

INTRODUCTION: The Belgian national External Quality Assessment Scheme performed a survey to assess the effect of the direct oral anticoagulant apixaban on the coagulation assays prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin as performed with a large number of reagent/instrument combinations. METHODS: Four lyophilized plasma samples spiked with apixaban (0, 41, 94 and 225 ng/mL) were sent to the 195 Belgian and Luxembourg clinical laboratories performing coagulation testing. RESULTS: PT and aPTT were barely influenced at the concentrations tested. At 225 ng/mL apixaban, PT and aPTT clotting times were only 1.15 times longer than at 0 ng/mL. Among PT reagents, RecombiPlasTin 2G® showed a slightly higher sensitivity with 225 ng/mL apixaban prolonging the PT clotting time 1.3-fold. Among aPTT reagents, there was no appreciable difference in sensitivity. Fibrinogen results were unaffected by the presence of apixaban, but antithrombin activity was considerably overestimated when measured with a FXa-based assay. At 225 ng/mL apixaban, the median percentage increase in antithrombin level was 31% when measured with the Liquid Antithrombin® reagent and 44% with the Innovance Antithrombin® reagent. CONCLUSION: Our data provide clinical laboratories with useful information on the impact of apixaban on their routine coagulation assays.

[Consequences of impacted wisdom teeth extraction on the periodontal environment of second molars. A pilot study]. / Conséquences de l'avulsion des dents de sagesse incluses sur l'environnement parodontal des deuxièmes molaires. Une étude pilote.

INTRODUCTION: Wisdom teeth extraction is a common procedure, generally considered as safe by patients. However, complications are possible, especially periodontal ones. The aim of this study was to evaluate the frequency and the consequences of periodontal complications at the level the 2nd molars after extraction of the wisdom teeth. MATERIAL AND METHODS: A single-center retrospective observational multi-operator study was conducted at the university hospital of Besançon - France. The files of all the adult patients who underwent extraction of four impacted wisdom teeth by mean of a standardized surgical technique between November 2012 and November 2014 and who could be followed 1 year postoperatively at least and that precisely mentioned the periodontal status of the surgical sites were included. Postoperative complications, gingival and plaque indexes according to Loë and Silness, periodontal attachment level and periodontal second molar probing were recorded. The main judgment criterion was the occurrence of a periodontal complication in the second molar areas. RESULTS: The files of 20 patients (15 women - 5 men), operated on by five different surgeons, met the inclusion criteria. Two patients suffered from dry socket at one of the avulsion sites. No patient had a gingival or plaque index greater than 2. No gingival recession or periodontal pocket over 4mm was found. DISCUSSION: Extraction of impacted third molars in young healthy adults didn't have any impact on the second molars periodontal environment in our study. Literature suggests that surgical technique greatly influences the occurrence and the extent of periodontal sequelae.

Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories.

Ensuring quality has become a daily requirement in laboratories. In haemostasis, even more than in other disciplines of biology, quality is determined by a pre-analytical step that encompasses all procedures, starting with the formulation of the medical question, and includes patient preparation, sample collection, handling, transportation, processing, and storage until time of analysis. This step, based on a variety of manual activities, is the most vulnerable part of the total testing process and is a major component of the reliability and validity of results in haemostasis and constitutes the most important source of erroneous or un-interpretable results. Pre-analytical errors may occur throughout the testing process and arise from unsuitable, inappropriate or wrongly handled procedures. Problems may arise during the collection of blood specimens such as misidentification of the sample, use of inadequate devices or needles, incorrect order of draw, prolonged tourniquet placing, unsuccessful attempts to locate the vein, incorrect use of additive tubes, collection of unsuitable samples for quality or quantity, inappropriate mixing of a sample, etc. Some factors can alter the result of a sample constituent after collection during transportation, preparation and storage. Laboratory errors can often have serious adverse consequences. Lack of standardized procedures for sample collection accounts for most of the errors encountered within the total testing process. They can also have clinical consequences as well as a significant impact on patient care, especially those related to specialized tests as these are often considered as "diagnostic". Controlling pre-analytical variables is critical since this has a direct influence on the quality of results and on their clinical reliability. The accurate standardization of the pre-analytical phase is of pivotal importance for achieving reliable results of coagulation tests and should reduce the side effects of the influence factors. This review is a summary of the most important recommendations regarding the importance of pre-analytical factors for coagulation testing and should be a tool to increase awareness about the importance of pre-analytical factors for coagulation testing.

[Arthrocentesis of the temporomandibular joint and intra-articular injections : An update]. / Arthrocentèse de l'articulation temporomandibulaire et injection(s) intra-articulaire(s) : un état des lieux.

INTRODUCTION: Arthocentesis of the temporomandibular joint combined with intra-articular washout and, more recently, intra-articular injection of pharmacological agents has been developed from the 1990s and is nowadays extensively in use for the treatment of temporomandibular dysfunctions (TMDs). The goal of our work was to answer 3 questions: 1. Is intra-articular washout effective for the treatment of TMDs ? 2. What kind of pharmacological agents may nowadays be injected in addition to washout and are these injections useful ? 3. What is the place of these treatments in the treatment strategies of TMDs ? MATERIAL AND METHODS: A bibliographic research has been carried out in the PubMed database using following keywords arthrocentesis, temporomandibular joint. The 27 articles published between 1991 and 2016, indicating patient's inclusion criterions and objectively evaluating the clinical results (mouth opening, intra-articular noises, pain) were selected. Pharmacological agents were noticed when used. RESULTS: 1. All authors concluded to the efficacy of intra-articular washout. No prognostic factor for arthrocentesis efficacy could be identified. 2. Main pharmacological agents used were steroids, hyaluronic acid, morphine-based drugs and platelet rich plasma. Superiority of ith-injection protocols failed to win unanimous support. All authors who compared with- and without-injection protocols concluded to the superiority of with-injection protocols, whatever the agent. DISCUSSION: Numerous studies have proven the efficacy of intra-articular washout for the treatment of TMDs resistant to noninvasive treatments. The advantage of any kind of pharmacological agent is not clear. Mechanisms of action are not all elucidated. No pharmacological agent showed any superiority over another. Study methodologies are often defective: imprecise inclusion criterions, short follow-up, confounding variables not taken into account, few comparison between pharmacological agents.

Facing coagulation disorders after acute trauma.

Facing coagulation disorders after acute trauma. PROBLEMS/OBJECTIVES: Trauma is the leading cause of mortality for persons between one and 44 years of age, essentially due to bleeding complications. METHODOLOGY: We screened the PubMed, Scopus and Cochrane Library databases, using specific keywords. Only publications in English were considered. MAIN RESULTS: The pathophysiology of trauma-induced coagulopathy (TIC) is complex and includes the classic "lethal triad" (i.e., haemodilution, acidosis, hypothermia) but may also include activation of protein C, endothelial and platelet dysfunction, and fibrinogen depletion. The time between trauma and treatment of the resultant massive bleeding should be as short as possible using techniques for rapid control of bleeding and avoiding aggravating factors (hypothermia, metabolic acidosis and hypocalcaemia). If given within three hours of injury, tranexamic acid (TXA) reduces all causes of mortality in trauma patients and reduces transfusion requirements. In a bleeding patient, crystalloids are preferred to colloids and the ratio of fresh frozen plasma to packed red blood cells should be at least 1:2. Damage control surgery (DCS) should be considered for patients who present with, or are at risk for developing, the "lethal triad", multiple life-threatening injuries or shock, and in mass casualty situations. DCS can also aid in the evaluation of the extent of tissue injuries and the control of haemorrhage and infection. Finally, there is currently no evidence of the added value of laboratory assays in the management of TIC. CONCLUSIONS: TIC appears quickly after trauma and should be anticipated and detected as soon as possible. TXA plays a central role in the management of such patients. Each institution should establish a local algorithm for the management of bleeding patients.

[Study of the normality of the orbito-naso-frontal bandeau]. / Étude de la normalité du bandeau orbito-naso-frontal.

INTRODUCTION: Craniosynostoses are cranio-facial malformations affecting about 1/2100 newborns in France. The involvement of anterior sutures (coronal and metopic) leads to orbito-frontal deformities. The treatment calls upon surgery the goal being, on an esthetic point of view, to restore a normal anatomy. The purpose of our work was to establish if some facial and/or frontal measures easy to perform on a CT are correlated to the global shape of the normal orbito-naso-frontal bandeau (ONFB). MATERIAL AND METHOD: Cranial CTs of 123 consecutive non-malformed children aged between 4 and 12 months were selected in the database of Department of Radiology of the University Hospital of Besançon - France. The CTs were all relocated by rigid transformation in an orthonormal coordinate system. On each of the 123 CTs, 21 reproducible measures representative of the global shape of the ONFB were made. Statistical analyses of these measures were achieved, considering age and gender, in order to determine the correlation between each measure and the ONFB shape. RESULTS: The only measure statistically correlated to the ONFB shape was the distance between the fronto-zygomatic sutures (FZD). The FZD was independent from age (in an interval of 4 months) and from gender. The 20 other measures did not show any correlation with age or gender. DISCUSSION: The FZD allows in itself to determine the ONFB global shape. This measure, easily available on a CT, can help the surgeon to perform a customized reshaping of the ONFB. The development of a surgical template using this measure is ongoing.

Recruitment and activation of circulating neutrophils after sinus surgery.

OBJECTIVE: After failure of pharmacological treatment, sinus surgery is the recommended alternative treatment for chronic sinusitis with or without nasal polyps. During post-operative healing, adequate local neutrophil activation plays an important role in the repair process. This pilot study aimed to systematically explore the participation of circulating neutrophils in early-phase wound repair of the nasal and paranasal mucosa after sinus surgery, with a special focus on neutrophil recruitment and activation patterns. METHODOLOGY: We conducted a single-center outcome study of patients undergoing sinus surgery. Whole blood samples were collected from eleven patients before surgery and at post-surgical time points of 1 hour and 1, 7, 14, and 30 days. Hematological analysis was conducted to count circulating neutrophils and evaluate their overall activation status. Using flow cytometry, neutrophil expression of membrane CD11b, CD11c, and CD15 was also measured, and oxidative burst analysis was performed. RESULTS: After sinus surgery, neutrophilia increased by 1 hour after surgery, reached a maximum at Day 1, and showed a gradual return toward baseline by Day 30. The oxidative burst initially decreased during the first hours after surgery, increased at Day 14, and returned toward normal by Day 30. Lewis X factor and the expression of CD11b and CD11c exhibited a bimodal change over time, in an inverted phase compared to the oxidative reaction. CONCLUSIONS: Circulating neutrophils are involved in the first phase of wound healing after sinus surgery as indicated by increased abundance, early membrane changes, and the modulation of their oxidative capacities.

[3D mandibular distraction planification in a case of severe temporomandibular ankylosis]. / Planification 3D d'une distraction mandibulaire dans le cadre d'une ankylose temporo-mandibulaire sévère.

INTRODUCTION: When occurring in childhood, temporomandibular ankylosis joint is responsible for complex maxillofacial deformities, including mandibular growth deficiency. We present a case of temporomandibular joint ankylosis associated with severe mandibular asymmetry treated by mandibular bone distraction performed under computer assistance. OBSERVATION: A 27-year-old patient presented with a severe facial asymmetry consisting in hypoplasia of the left hemi-mandible and maxilla. Mouth opening was non-existent. The CT-scan showed a left temporomandibular ankylosis. A left mandibular distraction was decided. The distraction characteristics (choice and positioning of the distractor, axis and amount of distraction) were determined preoperatively on the 3D CT-scan. The planning has been transferred to a navigation console (Kolibri®, Brainlab®). A combined intraoral and cutaneous was performed. Navigation allowed for an appropriate placement of the osteotomy line and fixation of the distractor. Distraction was started at the 5th postoperative day at the rate of 1mm per day and lasted 25 days without complication. DISCUSSION: 3D planning allows for better indication setting, better preparation of the procedure, reducing complications and operative time. It may help as an educational tool for young surgeons and for a better understanding from the patient. Navigation is an accurate method for the transfer of the planning in the operation room.

Rapid exclusion of the diagnosis of immune HIT by AcuStar HIT and heparin-induced multiple electrode aggregometry.

BACKGROUND: Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential but remains challenging. We have previously demonstrated, in a retrospective study, the usefulness of the combination of the 4Ts score, AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) with optimized thresholds. OBJECTIVES: We aimed at exploring prospectively the performances of our optimized diagnostic algorithm on suspected HIT patients. The secondary objective is to evaluate performances of AcuStar HIT-Ab (PF4-H) in comparison with the clinical outcome. METHODS: 116 inpatients with clinically suspected immune HIT were included. Our optimized diagnostic algorithm was applied to each patient. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) of the overall diagnostic strategy as well as AcuStar HIT-Ab (at manufacturer's thresholds and at our thresholds) were calculated using clinical diagnosis as the reference. RESULTS: Among 116 patients, 2 patients had clinically-diagnosed HIT. These 2 patients were positive on AcuStar HIT-Ab, AcuStar HIT-IgG and HIMEA. Using our optimized algorithm, all patients were correctly diagnosed. AcuStar HIT-Ab at our cut-off (>9.41 U/mL) and at manufacturer's cut-off (>1.00 U/mL) showed both a sensitivity of 100.0% and a specificity of 99.1% and 90.4%, respectively. CONCLUSION: The combination of the 4Ts score, the HemosIL® AcuStar HIT and HIMEA with optimized thresholds may be useful for the rapid and accurate exclusion of the diagnosis of immune HIT.

Platelet microparticle generation assay: a valuable test for immune heparin-induced thrombocytopenia diagnosis.

BACKGROUND: Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is essential to improve clinical outcome but remains challenging. The release of platelet microparticles (PMPs) is considered of major pathophysiological significance. OBJECTIVES: The aim of this study was to evaluate performances of PMP generation assay (PMPGA) compared to clinical outcome to diagnose HIT. The second objective was to compare PMPGA with performances of (14)C-serotonin release assay (SRA) on the same series of patients. METHODS: Sera of 53 HIT-suspected patients were retrospectively incubated with citrated-whole blood from healthy donors with 1IU and 500IU/ml of unfractionated heparin (UH). PMPGA was performed using FACSAria® flow cytometer. The clinical diagnosis was established by two blinded independent investigators analysing in a standardized manner the patient's medical records. Performances of PMPGA and SRA (n=53) were evaluated using ROC curve analysis with clinical outcome as reference. RESULTS: In positive HIT patients, PMPs expressing phosphatidylserine are generated with low UH concentration whereas PMP rate decreases significantly in presence of high UH concentration. Using clinical outcome as reference, sensitivity and specificity of PMPGA reached 88.9% (95% CI: 50.7-99.4) and 100.0% (95% CI: 90.0-100.0). Sensitivity and specificity of (14)C-SRA were 88.9% (95% CI: 50.7-99.4) and 95.5% (95% CI: 83.3-99.2). CONCLUSIONS: PMPGA is a rapid and reliable assay for HIT diagnosis. PMPGA showed good correlation with (14)C-SRA performances and predominately with clinical outcome.

Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: a retrospective study.

BACKGROUND: Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. OBJECTIVES: We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. METHODS: Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n=81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. RESULTS: Using the recommended thresholds (1.00AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89AU, HIT-Ab: 9.41AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. CONCLUSION: Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV.

Comparison of calibrated dilute thrombin time and aPTT tests with LC-MS/MS for the therapeutic monitoring of patients treated with dabigatran etexilate.

Ways to monitor dabigatran etexilate (DE) therapy would be useful in certain situations. Functional assays such as aPTT or Hemoclot® Thrombin Inhibitor (HTI) have been proposed to evaluate dabigatran concentrations, but previous findings are based on in vitro studies and results must be confirmed in clinical samples. The aim of this study was to compare aPTT and HTI measurements with liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurements of dabigatran in plasma samples from DE treated patients. Seventy-one plasma samples were included. aPTT was performed using STA-CKPrest® and SynthASil®. HTI was performed according to instructions from the manufacturer. The LC-MS/MS method utilised dabigatran-d3 as internal standard. The plasma concentration range was 0 to 645 ng/ml as measured by LC-MS/MS. Overall, the HTI and LC-MS/MS analyses correlated well (r²=0.97). The Bland-Altman analysis showed a mean difference of 9 ng/ml (SD: 20 ng/ml). However, the HTI performed poorly at concentrations <50 ng/ml. LC-MS/MS was sensitive (limit of quantification 1.1 ng/ml) and specific for dabigatran. The aPTT methods did not correlate well with plasma concentrations measured by LC-MS/MS (r² = 0.59 with SynthASil® and 0.50 with STA-CKPrest®). In conclusion, the poor sensitivity, the important inter-individual variability, and the poor correlation with LC-MS/MS preclude the use of aPTT to estimate dabigatran concentrations. Due to its small inter-individual variability and good agreement with LC-MS/MS measurements, we recommend the use of HTI assays to rather accurately estimate concentrations of dabigatran >50 ng/ml. Quantification of lower dabigatran levels in DE-treated patients requires the "reference" LC-MS/MS method.