[Acceptance of voluntary termination of pregnancy in the French 18-to-24-year-old population in 2021]. / Acceptation du recours à l'interruption volontaire de grossesse chez les Français de 18­24 ans en 2021.

OBJECTIVES: report on acceptance of voluntary interruption of pregnancy in 2021 in the French 18-to-24-year-old population and to compare the results with the acceptance reported in 2014 in the Institut Français d'Opinion Publique survey. METHODS: A French cross-sectional study with questionnaires administered between February and April 2021. The target population was 18 to 24 years of age. For purposes of comparison, the question on acceptance of voluntary interruption of pregnancy was basically the same as that of the 2014 Institut Français d'Opinion Publique survey, as were the proposed response modalities. Data were described in terms of means ± standard deviation and number (percentage). Conditions for acceptance of voluntary interruption of pregnancy were compared with the results of the 2014 Institut Français d'Opinion Publique survey using the Chi-square test. Factors associated with acceptance of voluntary interruption of pregnancy without restrictive conditions were studied using univariate analysis (Student, Chi-square or Fisher exact tests) and multivariate analysis (logistic regression). RESULTS: Close to 2000 (1936) questionnaires were completed, including 1225 among 18-to-24-year-olds. Voluntary interruption of pregnancy was accepted without restrictive conditions by 92.1% of the study population (95%CI: 90.4-93.5) compared to 79.0% in 2014 (p < 0.0001). Female gender (93.4 % versus 85.8%; OR = 2.1 [1.4-3.4]; p = 0.0009) and residence outside of Paris (94.9% versus 86.6%; OR = 2.8 [1.9-4.3]; p < 0.0001) were significantly associated with acceptance of voluntary interruption of pregnancy without restrictive conditions. CONCLUSION: In 2021 in France, the 18-to-24-year-old population is massively favorable to voluntary interruption of pregnancy without restrictive conditions, in a significantly higher proportion than in 2014.

Shoulder and Neck Balance in Adolescent Idiopathic Scoliosis: Which Radiographic Indices are Reliable and Practical?

Introduction: Deformities of the spine and thorax in adolescent idiopathic scoliosis affect appearance. They are a cause of inferiority, affecting psychological well-being and the social life of the patients. To contribute to curve evaluation, planning in curve correction, and improving the post-operative aesthetics, many studies on the correlation between appearance and radiography in the assessment of shoulder and neck balance have been reported recently. In general, these studies did not clarify which indices are required to evaluate shoulder and neck balance. This study aimed to learn about indices to assess shoulder and neck balance in adolescent idiopathic scoliosis in correlation between clinical appearance and radiography. Materials and methods: This observational study recruited 50 patients with adolescent idiopathic scoliosis who were 12 to 18 years of age with Cobb angle >10°. Based on Pearson correlation coefficient, radiographic parameters such as coracoid height difference (CHD), clavicle rib intersection distance (CRID), clavicle angle (CA), clavicle chest cage angle difference (CCAD), and T1 tilt angle were evaluated in correlation with clinical shoulder and neck balance by difference of inner shoulder height (SHi), difference of outer shoulder height (SHo), and neck tilt angle. Results: SHi was moderately correlated with T1 tilt angle (r [hereafter] = 0.45), CA (0.47), and CHD (0.57), high-moderately correlated with CRID (0.64), very-highly correlated with CCAD (0.84). SHo was moderately correlated with T1 tilt angle (0.43), highly correlated with CHD (0.60), CA (0.63), and CRID (0.72), and very-highly correlated with CCAD (0.89). T1 tilt angle was high-moderately correlated with neck tilt angle (0.76). The correlation coefficients between clinical and radiographic shoulder and neck balance according to sex, BMI, type of main curve, severity of main curve did not change significantly. Conclusion: There was a very high correlation between SHo (shoulder tilt) and CCAD (0.89); the correlation between SHo and CRID was high-moderate (0.72), but CRID is easier than CCAD to evaluate on radiographs. On the other hand, T1 tilt angle, which is the easiest radiographic parameter to evaluate, had a high-moderate correlation with neck tilt angle (0.76) but a moderate correlation with SHo (0.43).

Evaluation of fibrosis in precision-cut tissue slices.

1.In this review, the use of precision-cut tissue slices (PCTS) of the liver, kidney, lung and intestine in fibrosis research are evaluated and future possibilities are discussed. 2.In vivo models or techniques that are applicabless to be investigated in PCTS are discussed. 3.It is concluded that the early onset of fibrosis can be induced successfully in PCTS prepared from human and experimental animals. 4.Moreover, precision-cut slices of fibrotic tissue are effective in gaining new knowledge of the mechanisms of fibrosis and of the mode of action of potential antifibrotic drugs. 5.Both healthy and fibrotic human tissue slices will pave the way for the testing of novel therapeutic drugs to treat patients with fibrosis avoiding interspecies extrapolation.

Net costs of hospital-acquired and pre-admission PUs among older people hospitalised in Ontario.

OBJECTIVE: To determine the net cost of hospital-acquired and pre-admission pressure ulcers (PUs) in an acute-care setting in Ontario, Canada. METHOD: Cases of PUs were identified among hospitalised patients using Ontario Case Costing Initiative (OCCI) data from 2002-2006. Inpatient costs included direct and overhead costs.To determine the net cost of PUs, cases were matched controlling for age, gender, most responsible diagnosis and comorbidity. Mean net costs were estimated using Bayesian linear mixed models methods. Results were also reported by PU severity. RESULTS: In our study, there were 1351 cases of hospital-acquired PUs and 2523 cases of preadmission PUs over 5 years. Net cost of hospital-acquired PU ranged between CA$44000 for a category II PU to CA$90000 for a category IV PU. For pre-admission PU net cost was between CA$11 000 to CA$18500 for category II and category IV PU, respectively.The net cost of treating hospital-acquired PU is higher than pre-admission PU. Costs increase with increasing PU severity. CONCLUSION: The total net adjusted hospitalisation cost of a hospital-acquired PU in Ontario was CA$44000-90000, compared with CA$11 000-18500 for a pre-admission PU. Future studies should determine the attributable cost of PU using patient-level data to verify the accuracy of the study results.

Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study.

OBJECTIVES: General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia. STUDY DESIGN: We performed a retrospective case-control study including singleton-laboring women with epidural analgesia who delivered after 37 gestational weeks by urgent cesarean (Port Royal Maternity unit, 2012-2017). Cases were all women who required conversion from neuraxial analgesia to general anesthesia. Controls were women just before and after each case included. Factors associated with the conversion to general anesthesia were identified using logistic regression analysis. RESULTS: Among 3,300 laboring women with an epidural analgesia who delivered by urgent cesarean during the study period, 113 (3.4%,) had a conversion to general anesthesia. Factors associated with conversion to general anesthesia were a cervical dilation ≥ 5 cm at the time of epidural placement (aOR 2.55, 95%CI 1.05-6.21), asymmetric sensory blockade (aOR 3.39, 95%CI 1.11-10.36), need for ≥2 rescue top-ups (aOR 2.88, 95%CI 1.29-6.44), and category 1 cesarean (aOR 3.61, 95%CI 1.77-7.33). CONCLUSION: Among women with labor epidural analgesia, suboptimal analgesia significantly increased the risk for conversion to general anesthesia for urgent cesarean. Epidural placement without delay during labor, regular checks of epidural analgesia efficiency, and epidural replacement in case of inadequate epidural analgesia may decrease the rate of avoidable general anesthesia for urgent cesarean.

Suspicion of drug-drug interaction between high-dose methotrexate and proton pump inhibitors: a case report - should the practice be changed?

We report a case of a potential drug-drug interaction in a woman treated by a first injection of high-dose methotrexate for a T-lymphoblastic lymphoma. Valaciclovir, fluoxetine and pantoprazole were given concomitantly. A methotrexate overdosage was shown at 36 h after infusion associated with a severe renal failure. Alkaline hyperhydration, folinic acid and carboxypeptidase G2 were given. Prescription analyses by pharmacists and literature research have permitted us to suggest that a drug-drug interaction between methotrexate and proton pump inhibitors (PPI) was responsible for this renal failure. Several mechanisms of interaction were suggested and might be related to the inhibition of renal methotrexate transporters by PPI, an increase in the methotrexate efflux to the blood by an upregulation of multidrug resistance protein 3 by PPI or genetic polymorphisms. This case shows that pharmacists can help physicians to optimize patient treatment: they consensually decided on the systematic discontinuation of PPI or a switch to ranitidine when patients were treated by high-dose methotrexate.

Facile colorimetric detection of Hg (II), photocatalytic and antibacterial efficiency based on silver-manganese disulfide/polyvinyl alcohol-chitosan nanocomposites.

The application of nano materials for removal and detection of hazardous metal detection with nanoparticles is important for researcher. In this paper, the silver-manganese disulfide/chitosan-polyvinyl alcohol (Ag-MnS2/CSPVA) nanocomposites was prepared for the detection of toxic heavy metal. The synthesized nano materials was experimented through the various analysis methods to structural and morphological evaluation. The surface charge of the Ag-MnS2/CSPVA was -25.0 ± 0.1 mV. The various metal ions have not effect on detection of mercury (II). The result shows the excellent linearity was found the mercury concentrations changing with limit of detection of 9.0 nM (nano molar level). The condition of detection was conducted at pH 5 and room temperature. Moreover, the photocatalytic properties of the Ag-MnS2/CSPVA nanocomposites was analyzed for degradation of malachite green under visible light irradiation. The complete malachite green degradation reached up to 97.29% after 30 min of photocatalytic reaction. The antibacterial efficiency was studied versus both Escherichia coli and Staphylococcus aureus bacteria. The outcome depicts that the Ag-MnS2/CSPVA nanocomposites has an excellent property in antibacterial activity.

Activation of membrane-associated procaspase-3 is regulated by Bcl-2.

The mechanism by which membrane-bound Bcl-2 inhibits the activation of cytoplasmic procaspases is unknown. Here we characterize an intracellular, membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2. Heavy membranes isolated from control cells contained a spontaneously activatable caspase-3 zymogen. In contrast, in Bcl-2 overexpressing cells, although the caspase-3 zymogen was still associated with heavy membranes, its spontaneous activation was blocked. However, Bcl-2 expression had little effect on the levels of cytoplasmic caspase activity in unstimulated cells. Furthermore, the membrane-associated caspase-3 differed from cytosolic caspase-3 in its responsiveness to activation by exogenous cytochrome c. Our results demonstrate that intracellular membranes can generate active caspase-3 by a Bcl-2-inhibitable mechanism, and that control of caspase activation in membranes is distinct from that observed in the cytoplasm. These data suggest that Bcl-2 may control cytoplasmic events in part by blocking the activation of membrane-associated procaspases.

Staining for intracytoplasmic lumina and CAM5.2 increases the detection rate for bile duct cancers.

BACKGROUND AND STUDY AIMS: Endoscopic biopsies have a low sensitivity for diagnosing malignant bile duct strictures. Tumor markers detected by mucin staining and immunohistochemistry may help to determine the malignancy of a biopsy specimen where histologic evaluation alone is nondiagnostic. PATIENTS AND METHODS: 61 patients who underwent forceps biopsies were retrospectively identified, yielding 49 and 40 biopsy specimens for strictures finally diagnosed as benign and malignant, respectively. Biopsy specimens were histologically evaluated and stained for p53, Ki-67, carcinoembryonic antigen (CEA), CA19-9, CAM5.2, and presence of intracytoplasmic lumina (ICL). Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated to evaluate the performance of each test. RESULTS: Histology alone provided sensitivity and specificity of 53 % and 100 %. Addition of ICL or CAM5.2 increased sensitivity to 73 % or 60 %, respectively, and provided excellent specificity, PPV, and PLR (ICL, 98 %, 97 %, and 36; CAM5.2, 100 %, 100 %, and infinite). Both stains in combination increased the sensitivity to 75 %. Staining for Ki-67, p53, CEA, and CA19-9 increased the sensitivity to detect malignancy (range 60 % to 83 %), but significantly reduced the specificity, PPV and PLR (ranges 73 % to 90 %, 72 % to 86 %, and 3 to 7, respectively). Markers in all combinations performed poorly as a negative test (NPV 69 % to 87 %, and NLR 0.19 to 0.55). CONCLUSIONS: Staining for tumor markers ICL and CAM5.2 can improve the diagnostic value of endoscopic biopsies, and may change the course of management for patients with indeterminate histological findings.

The use of one-channel water cystometry in patients with a spinal cord lesion: practicalities, clinical value and limitations for the diagnosis of neurogenic bladder dysfunction.

STUDY DESIGN: Investigational technique evaluation. OBJECTIVE: To evaluate the clinical value and limitations of one-channel cystometry as a method for urodynamic testing in patients with spinal cord lesion (SCL). SETTING: Spinal Cord Injury Centers Asia. METHODS: Protocol, equipment and practical performance of the one-channel cystometry as used in Ho Chi Minh City and Chiang Mai were studied. RESULTS: One-channel cystometry permits to accurately evaluate bladder pressure development at constant filling speed. It shows detrusor muscle behaviour as detrusor overactivity and allows evaluating sensation of bladder filling. It can strongly suggest detrusor external sphincter dyssynergia. The need of bladder-relaxant drugs and their effectiveness can be evaluated. The major limitation is that the one pressure line will show changes of intravesical pressure independent of their cause, which makes a continuous thorough observation mandatory throughout the test. Other limitations are a filling rate higher than physiological and a filling solution at room temperature. As in more elaborate urodynamic testing, the observations do therefore not necessarily reflect the function of the lower urinary tract in daily life. CONCLUSION: One-channel cystometry is easy to perform, cheap and clinically valid. The results need to be integrated in the overall knowledge of the patient's neurological situation. The method permits one to gather a lot of information on bladder function in persons with SCL. With proper interpretation and a clear understanding of the shortcomings, it is a good guide for bladder management. It is applicable everywhere.

Transfusion of rare cryopreserved red blood cell units stored at -80 degrees C: the French experience.

The technology allowing freezing of RBC units has been available for many decades. The high-glycerol method for RBC storage at -8 degrees C is predominantly used. Several studies have shown satisfactory results regarding the in vitro viability and function of cryopreserved RBCs. RBC freezing is nowadays mostly encountered in rare blood programs and military deployments. Preservation time of frozen RBCs appears to be virtually indefinite, but most countries apply a 10-year outdate. There is no mandatory time restriction in France. The National Rare Blood Bank currently includes 962 (17.5%) RBC units aged to years or more and 153 (2.8%) aged 20 years or more. Since 1994, 1957 RBC units have been thawed and transfused, among which 118 were aged 10 years or more and 8 were aged 20 years or more. Discarding RBC units older than to years may be highly sensitive for very rare blood groups, e.g., U-, of which approximately 30 percent of the cryopreserved units are aged to years or more. However, the lack of nucleic acid testing for HIV and HCV may be problematic for old RBC units drawn from donors who were not subsequently tested for these markers, which is now mandatory in most countries. Regarding the 118 transfused RBC units older than 10 years, no evidence of hemolysis of thawed RBCs and no transfusion reaction, clinical or biologic hemolysis, or transfusion ineffectiveness was reported, either by any of the parties involved in the transfusion supply of rare RBC units or through the French hemovigilance program, which requires a mandatory report of any transfusion reaction. It has recently been suggested to extend the 10-year restriction in some countries. Considering our experience and observational data, we may consider it safe and efficient to transfuse rare frozen RBC units older than 10 years. An international consensus for RBC cryopreservation time should ideally be established.

[The red blood cell antigen terminologies]. / Les nomenclatures de groupes sanguins érythrocytaires.

Since the discovery of blood groups in humans, several hundred new red blood cell antigens have been identified. Multiple terminology modes have been used to denote each new antigen identified, but without any consistent rules, nor international consensus. This was largely due to the many discoverers of these antigens, using either letters of the alphabet, numbers, part of the patient or donor's name, place of discovery or animal names. Besides, alternative terminologies for the Rh system were implemented in the middle of the twentieth century (Rosenfield, Fisher-Race, Wiener). The International Society of Blood Transfusion described for the first time in 1980 the advantages of an alphanumeric and homogeneous nomenclature, keeping with the genetic bases of blood groups, as well as a classification of all RBC antigens within several families. A variant of this new terminology, exclusively numerical, was simultaneously established, mainly designed for computer data exchange. Nearly 30 years later, 308 red blood cell antigens are described within 30 systems, 12 collections, one 700 series and one 901 series of blood groups. Any person involved in the field of immuno-haematology must master both the usual and international nomenclatures. The Wiener nomenclature used for Rh haplotypes, still largely used today, is also important to be known. The systematic use of the international nomenclature should be strongly encouraged, either in the labelling of blood products, clinical laboratory reports or blood type cards.

[Genotyping of blood group systems at the CNRGS. I: FY, JK, MNS systems]. / Génotypage des systèmes de groupe sanguin d'intérêt transfusionnel au CNRGS. I: les systèmes FY, JK, MNS.

AIM OF THE STUDY: Determination of blood group antigens from data obtained by using molecular methods (genotyping) has become an indispensable tool in the specialized immunohematology laboratories. The French National Reference Centre for Blood group typing (CNRGS) routinely performs genotyping of the FY, JK and MNS system (common genotyping), providing a phenotype deduced from genotyping data for FY1, FY2, JK1, JK2, MNS3 and MNS4 antigens. PATIENTS AND METHODS: We performed a study to evaluate the common genotyping prescriptions referred to the CNRGS over the last three years. RESULTS: Between February 2006 and February 2009, the CNRGS performed 2392 genotyping, including 981 common genotyping. Analysis of 172 common genotyping performed in 2008 showed that 63.8% of the prescriptions expressed a genotyping demand. Of the latter, 42.7% were genotyping prescriptions only, whereas 57.2% were prescriptions of genotyping associated with alloantibody identification. All prescriptions refer to blood group genotyping indications issued from guidelines, with no incorrect prescription, that are patients transfused within four months before blood sampling in 63.6% of cases or a positive direct antiglobulin test in 24.5% of cases. Lastly, 36% of the blood samples referred to the CNRGS had no genotyping prescription. Yet, common genotyping was performed by the CNRGS to get complete immunohematology data for antibody identification. CONCLUSION: Usefulness of blood group genotyping in specialized immunohematology laboratories is obvious. However, the strategy for implementation of molecular methods remains to be defined. Use of high-throughput DNA analysis should change our way of working.

[National external quality assessment in auto-immunity: antineutrophil cytoplasmic antibodies]. / Contrôle national de qualité en auto-immunité : anticorps anticytoplasme des polynucléaires neutrophiles.

The French Health Products Safety Agency organized in 2007, for the scheme of the national external quality assessment, a survey on antineutrophil cytoplasmic antibodies (ANCA) including detection and identification of the antibodies. This survey allowed to assess the quality of the different methods of these assays. The detection of ANCA by the indirect immunofluorescence technique was satisfactory. However, the methods of identification gave a high rate of false negative results for the anti-myeloperoxidase antibodies (anti-MPO), especially with the immunodot technique. Concerning the titer of anti-MPO antibodies obtained by ELISA, the broad dispersion of results between reagents pointed out a lack of standardisation of the detection of these antibodies.

[Updates in systemic sclerosis pathogenesis: Toward new therapeutic opportunities]. / Actualités dans la physiopathologie de la sclérodermie systémique : vers de nouvelles opportunités thérapeutiques.

Systemic sclerosis is a rare connective tissue disease characterized by skin and several internal organ fibrosis, systemic vasculopathy and immune abnormalities. Even if fibroblasts and endothelial cells dysfunction, as well as lymphocytes and other immune cells implication are now well described, the exact origin and chronology of the disease pathogenesis remain unclear. Oxidative stress, influenced by genetic and environmental factors, seems to play a key role. Indeed, it seems to be implicated in the early phases of fibrosis development, vasculopathy and in immune tolerance abnormalities shared by all patients, although disease expression is heterogeneous. To date, no curative treatment is available. Even if immunosuppressive treatment or drugs acting on vascular system are proposed for some patients, overall, treatment efficiency remains modest. Only autologous hematopoietic stem cells transplantation, reserved for patients with severe or rapidly progressive fibrosis, has recently demonstrated efficiency, with lasting regression of fibrosis. Nevertheless, this treatment can expose to important, life-threatening toxicity. In the last decade, new mechanisms implicated in the pathogenesis of systemic sclerosis have been unraveled, bringing new therapeutic opportunities. In this review, we offer to focus on recent insights in the knowledge of systemic sclerosis pathogenesis and its implication in current and future medical care.

Pilot comparison of adhesion formation following colonic perforation and repair in a pig model using a transgastric, laparoscopic, or open surgical technique.

BACKGROUND AND STUDY AIM: Postoperative adhesions create significant morbidity and mortality. Natural orifice transluminal endoscopic surgery (NOTES) procedures may reduce or eliminate adhesions by avoiding disruption of the parietal peritoneum. The primary aim of this pilot study was to compare adhesion formation after performance and subsequent repair of colonic perforation via transgastric, laparoscopic, or open surgical techniques. The secondary aim was to test the feasibility and outcome of transgastric management of bowel perforation in a prepared model. MATERIAL AND METHODS: 15 Yorkshire pigs were divided into three groups of five: transgastric (needle-knife entry with balloon dilation over a wire), laparoscopic, and open surgical. Aspects of adhesion formation (density/vascularity, width of bands, and number of organ pairs involved) were compared after perforation and repair during the same procedure. Intra- and postoperative complications were documented during the 21-day survival period. RESULTS: All 15 pigs recovered fully with no immediate procedural complications. After 21 days, there was a trend towards a lower adhesion burden regarding density/vascularity and number of organ pairs involved, and a significant reduction in the width of the adhesive bands, when the transgastric group was compared with the surgical groups. Additionally, there was a trend towards decreased adhesions to the peritoneum in the transgastric group. CONCLUSIONS: Repair of colonic perforation during transgastric (NOTES) procedures appear feasible and safe in a porcine model. There appears to be a trend towards a lower rate of adhesion formation with the transgastric approach compared with laparoscopic or open surgery.

Pilot series of radiofrequency ablation of Barrett's esophagus with or without neoplasia.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation is a rapidly evolving therapeutic modality for Barrett's esophagus. The aim of this ongoing 12-month trial is to assess Barrett's esophagus eradication after radiofrequency ablation using a balloon-based (HALO-360) and a plate-based (HALO-90) device. We report here our experience with the first 10 patients (out of 40) who have completed 12 months of follow-up. PATIENTS AND METHODS: Following radiofrequency ablation using the HALO-360 device all patients were maintained on double-dose proton pump inhibitor therapy. Endoscopic evaluation was performed at 3 and 12 months postablation. Patients with residual Barrett's esophagus at 3 months underwent repeat ablation. Ten patients, seven with nondysplastic Barrett's esophagus, two with low-grade and one with high-grade dysplasia have completed the study to date. RESULTS: Complete Barrett's esophagus eradication was achieved in seven patients, and partial eradication was achieved in three. There were no major complications. One case of buried Barrett's metaplasia was encountered and successfully re-ablated, with complete Barrett's esophagus eradication achieved at 12 months. CONCLUSIONS: In this study, Barrett's eradication rates were comparable to previously published reports. One case of buried Barrett's metaplasia was identified out of 247 biopsies and was eradicated with repeat ablation.

[The rare blood groups: a public health challenge]. / Les phénotypes érythrocytaires rares: un enjeu de santé publique.

A rare blood group is usually defined as the absence of a high prevalence antigen or the absence of several antigens within a single blood group system, if its prevalence in France is 4/1000 or less in the general population. An individual with a rare blood phenotype can develop a naturally-occurring or immune antibody corresponding to his rare specificity. In case an extremely low stock of compatible blood is available at the national level, a so-called "transfusion deadlock" is described. Most of the individuals with a rare blood group are coincidently identified when a routine pretransfusion testing or pregnancy follow-up is performed, if the antibody(ies) corresponding to the rare specificity is(are) present. Other individuals are discovered following a systematic red cell typing, or family investigations in siblings. One hundred and twenty-one rare blood specificities and 42 rare blood genotypes are currently defined at the French National Reference Laboratory for Blood Groups (CNRGS-Paris). The French national registry of individuals with a rare blood phenotype/genotype includes about 9600 people, who are urged to regularly donate blood for the National Rare Blood Bank. This bank, based on a homologous blood transfusion program, is in charge of the long-term storage of rare frozen blood units, that can only be delivered after receiving authorization from the CNRGS. The global and individual care management of the individuals with a rare blood group, concerning potentially several hundred thousand people in France, requires a close cooperation between all the protagonists within the transfusion chain.

Quantitative comparison of the neutralizing capacity, immunogenicity and cross-reactivity of anti-TNF-α biologicals and an Infliximab-biosimilar.

INTRODUCTION: TNF-α-neutralizing antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective in the treatment of inflammatory bowel diseases (IBD), but they are expensive and become ineffective when patients develop anti-IFX or anti-ADA antibodies (ATI and ATA, respectively). Second-generation anti-TNF-α antibodies, such as Golimumab, Etanercept, Certolizumab-pegol and IFX biosimilars, may solve these issues. AIM: To determine the neutralizing capacity of first- and second generation anti-TNF-α antibodies and to determine whether ATI show cross-reactivity with the IFX biosimilar CT-P13 (Inflectra). METHODS: TNF-α neutralization was measured using a quantitative TNF-α sensor assay consisting of HeLa 8D8 cells that express the Green Fluorescence Protein (GFP) under control of a NF-кB response element. All available anti-TNF-α drugs and the IFX biosimilar CT-P13 (Inflectra) were tested for their TNF-α-neutralizing capacity. In addition, patient sera with ATI were tested for their potential to block the activity of IFX, IFX (F)ab2-fragment, biosimilar CT-P13 (Inflectra) and ADA. RESULTS: TNF-α strongly induced GFP expression in Hela 8D8 cells. Higher concentrations of first-generation anti-TNF-α drugs were required to neutralize TNF-α compared to the second-generation anti-TNF-α drugs. Serum of IBD patients with proven ATI blocked TNF-α-neutralizing properties of IFX biosimilar CT-P13 (Inflectra), whereas such sera did not block the effect of ADA. CONCLUSION: The second-generation anti-TNF-α drugs show increased TNF-α-neutralizing potential compared to first-generation variants. ATI show cross-reactivity toward IFX biosimilar CT-P13 (Inflectra), consequently patients with ATI are unlikely to benefit from treatment with this IFX biosimilar.