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).

[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.

[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.

[Red-blood-cell allo-immunization]. / Allo-immunisation anti-érythrocytaire.

Red blood cell allo-immunization is the immune response of an individual to foreign red blood cell antigens not present on the surface of their own cells. The aim of that paper is to clarify the different factors influencing the antibody response against red blood cell antigens.

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.

Blood group genotyping by high-throughput DNA analysis: application to the French panel of RBC reagents.

BACKGROUND: The use of blood group genotyping for the prediction of antigen expression has been discussed in clinical transfusion settings, but much less for reagent red blood cells selection. In France, the Centre National de Référence pour les Groupes Sanguins (CNRGS) produces a reference panel of reagent red blood cells, mainly used for red cell antibody identification. The use of high-throughput DNA analysis has never been applied to blood donors whose red blood cells are used as reagents. The aim of this study was to compare the serological phenotype and that predicted from DNA analysis in such donors, and to determine the benefit of DNA analysis in reagent red blood cells selection strategy. STUDY DESIGN AND METHOD: Red blood cells of 346 blood donors were typed with two different reagents for each antigen. The genotyping was performed by using HEA v1.2 BeadChips, BioArray Solutions, Immucor. The comparison between the serologically determined phenotype and that predicted from DNA analysis held on 8876 paired results obtained from 10 blood group systems and 25 antigens. RESULTS: A 99.95% concordance was observed. Four cases of discrepancy for RH, KEL, LU and DO blood group systems were analyzed. Genotyping precisions were of special interest for the Duffy blood group system. CONCLUSION: Systematic DNA analysis brings important information on reagent red blood cells selection. It can be used at a routine level. Especially, the notion of "antigen of double dose" which is specified in several countries by government bodies should evolve regarding data obtained from DNA analysis. This should improve the quality of reagent red blood cells as first step for antibody identification.

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.

[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.

[National external quality assessment in auto-immunity: auto-antibodies against thyroid constituents]. / Contrôle national de qualité en auto-immunité: anticorps anti-thyroïdiens.

The French Health Products Safety Agency organized in 2005, for the scheme of the national external quality assessment, a survey on antibodies against thyroid constituents which included for the first time the quantitative assay. The purpose of this survey was to assess the quality of the different methods of these assays. The overall qualitative results are satisfactory. However, this survey pointed out a lower performance for immunodot which appeared to have been misused. Concerning the titer of antibodies, results show a broad dispersion between reagents. This confirms the lack of a real standardisation despite of the existence of the international MRC standards.

Quantitative measurement of hepatitis C virus core antigen is affected by the presence of cryoglobulins.

Mixed cryoglobulinaemia is associated strikingly with HCV infection. The aim of this study was to assess whether the adherence to proper methods of collecting samples for cryoglobulin detection was critical or not on virological parameters in hepatitis C virus (HCV) patients. We studied 56 consecutive patients. Blood samples were collected using a conventional method and a blood collection method at 37 degrees C adapted to cryoglobulin detection. HCV core antigen and HCV RNA were measured in sera and cryoglobulins issued from both blood collection methods. In cryoglobulin-positive patients, serum concentrations of HCV core antigen, but not that of HCV RNA, were significantly higher when a conventional method was used, compared to a blood collection method at 37 degrees C (P = 0.001). In the cryoprecipitates, concentration of HCV core antigen was optimum when the blood collection method at 37 degrees C, rather than the conventional method, was applied for cryoglobulin detection (P < 10(-4)). The recovery of HCV core antigen in the cryoprecipitate was improved when cryoglobulins were isolated using the blood collection method at 37 degrees C rather than the conventional method (P < 0.001). HCV parameter measurements and cryoglobulin study should not be performed on the same serum samples due to the potential impact of blood collection methods on results.

Accurate model predicting sustained response at week 4 of therapy with pegylated interferon with ribavirin in patients with chronic hepatitis C.

Current models used to predict response to peginterferon plus ribavirin treatment, based on viral decline during the first 12 weeks of therapy, have focused on creating an early stopping rule to avoid unnecessary prolongation of therapy. We developed a multivariate model that predicted sustained virological response and nonresponse at baseline and during the first 12 weeks of therapy using collected data from 186 unselected patients with chronic hepatitis C treated with peginterferon plus ribavirin. This model employed ordinal regression with similarity least squares technology to assign the probability of a given outcome. Model variables include sex, age, prior treatment status, genotype, baseline serum alanine aminotransferase levels, histologic necroinflammation and fibrosis scores and serum hepatitis C virus RNA concentration at baseline and weeks, 4, 8, and 12. A multivariate model demonstrated high performance values at all time points. At baseline, the model demonstrated a negative predictive value (NPV) and a positive predictive value (PPV) of 91% and 95%, respectively. At week 4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89% specificity and 93% accuracy. At week 4, the model was equally efficient for naïve or previously treated patients. Internal validation demonstrated 90% PPV, 94% NPV, 95% sensitivity, 88% specificity and 92% accuracy. A week 4 stopping rule for patients with chronic hepatitis C treated with peginterferon with ribavirin might be proposed by using the model developed in our study.

[National external quality assessment in auto-immunity: autoantibodies detected on liver, kidney and stomach tissues]. / Contrôle national de qualité en auto-immunité: anticorps anti-tissus non spécifiques d'organe.

In 2003, for the scheme of the French national external quality assessment, Afssaps organized for the first time a survey on auto-antibodies detected on liver, kidney and stomach tissues. This survey had two purposes: first to make an inventory of the methodology applied by the medical laboratories and secondly to assess the quality of the results. The survey sample contained M2 anti-mitochondrial antibodies. Overall results are satisfactory. Concerning the titer of antibodies, a broad dispersion of results was observed (12% of titers were upper than the expected titer). Delivered information to the participants, at the end of the survey, should improve analytical procedures applied by the biologists. An effort of standardization by using titrated internal controls would be suitable.

Impact of external quality assessment on antinuclear antibody detection performance.

Our objective was to evaluate performance of the clinical laboratories for the detection of antinuclear antibodies (ANA) by using indirect immunofluorescence method (IIF), in France. A national external quality assessment (EQA) on ANA detection was organized by the French health products safety agency once a year since 1998. Between 606 to 687 laboratories together with six university reference laboratories experienced in performing tests in autoimmunity participated in the six-year consecutive survey. Each laboratory had to answer to methodological procedures and give coded responses. Variability in IIF methodological procedure was observed. Use of inappropriate microscope magnifications for reading slides or nonconventional cutoff dilution of serum were pointed out to concerned laboratories. Concerning ANA measurement, the rate of good responses ranged from 92.7% to 99.5% of the laboratories when the samples contained ANA. A wide dispersion of ANA titers obtained on a same sample was repeatly observed every year. Misinterpretation of particular fluorescence pattern was noticed. On ANA negative sample, the rate of good responses was 94.3%. In conclusion, ANA detection in routine practice is far from being standardized. However, EQA may have an impact on ANA detection performance when it is conducted on several consecutive year surveys, by providing advice for participating laboratories to limit inter laboratory variations related to methodological procedures.

[Monoclonal immunoglobulin: national external quality assessment and diagnostic reasoning]. / Immunoglobuline monoclonale: contrôle national de qualité et démarche diagnostique.

In 2003, for the scheme of the French national external quality assessment, Afssaps sent to medical laboratories a sample for which two analyses could be carried out: the electrophoresis of proteins and the characterization for monoclonal immunoglobulin. The purpose of this new approach was to make it possible to the laboratories to transpose their usual diagnostic reasoning. This survey recalled to the biologists that it is necessary to check the sensitivity of the test of electrophoresis of proteins used in first intention and to use advisedly the anti-serums anti-free chains. Moreover this operation reinforced the educational aspect of the external quality assessment, pointing out the importance to ensure the coherence of the results of these two analyses carried out with a same diagnostic aim.

Association of idiopathic hepatic sinusoidal dilatation with the immunological features of the antiphospholipid syndrome.

BACKGROUND: Isolated sinusoidal dilatation is an uncommon hepatic lesion and the cause is largely unknown. OBJECTIVE: To investigate whether prothrombotic disorders or perisinusoidal cell changes could be involved in pure idiopathic hepatic sinusoidal dilatation (HSD). METHODS: Evaluation for associated conditions, prothrombotic disorders, and studies of hepatic perisinusoidal cell activation in consecutive patients, seen between 1993 and 2002, with isolated sinusoidal dilatation unrelated to outflow block, sinusoidal infiltration, or hepatic granulomas. RESULTS: Among 11 patients, associated conditions were prothrombotic disorders (n = 5) and oral contraceptive use (n = 3). Prothrombotic disorders were polycythemia vera (n = 1) and anticardiolipin antibodies combined with lupus anticoagulant (n = 4). No genetic thrombophilia factor was found. Of four patients with lupus anticoagulant, three had antinuclear factors and high serum levels of anticardiolipin antibodies at repeated testing. There was no evidence of intrahepatic or extrahepatic thrombosis in any of the patients. Sinusoidal dilatation was marked in six of 11 patients (54%), including two patients with antiphospholipid antibodies. Activated perisinusoidal cells were only found around markedly dilated sinusoids. CONCLUSION: Idiopathic pure HSD is frequently associated with the immunological features of the antiphospholipid syndrome. Therefore, finding pure HSD in a liver biopsy specimen should prompt the search for antiphospholipid antibodies.

Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence.

AIM: To evaluate 5-year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow-up. METHODS: In a non-concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow-up. RESULTS: The 5-year survival rates were 43% in the 122 patients and 66%, 50% and 25% in Child-Pugh class A, B and C patients, respectively. In multivariate analysis, age (P = 0.01), Child-Pugh score (P = 0.0001), gastrointestinal bleeding (P = 0.01), presence of HBs Ag and/or anti-HCV (P = 0.03), smoking (P = 0.01), absence of histologically proven alcoholic hepatitis (P = 0.05) and persistent alcohol intake (P = 0.002) were associated with significantly increased risk ratios of death. CONCLUSIONS: In hospitalised patients with excessive alcohol intake and cirrhosis: (1) age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are independent poor prognostic markers, (2) smoking may contribute to the aggravation of cirrhosis, and (3) alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favourable prognostic significance.