Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

Particularités de prise en charge chirurgicale des goitres pluri-nodulaires bénins à l'Hôpital d'Instruction des Armées de Cotonou, Bénin

Introduction : Le goitre "bénin" est une hypertrophie diffuse de la thyroïde normo-fonctionnelle, non-inflammatoire et non-cancéreuse. Le but de la présente étude était d'analyser les particularités de prise en charge des goitres pluri-nodulaires relevant d'une indication chirurgicale. Matériel et méthode : Cette étude de cohorte rétrospective a été réalisée du 1er janvier 2013 au 1er janvier 2018 à l'Hôpital d'Instruction des Armées - Centre Hospitalier Universitaire de Cotonou, Bénin. Ont été inclus les patients opérés pour goitre pluri nodulaire bénin. Ont été exclus les patients atteints de pathologies thyroïdiennes non nodulaires ou de cancer thyroïdien. Les données étudiées ont été : l'âge, le sexe, la profession, le lieu de résidence, le motif de consultation, les signes cliniques, les signes échographiques, la prise en charge chirurgicale, les complications per et post-opératoires et l'histologie définitive de la pièce d'exérèse. Ces données ont été colligées à l'aide du logiciel Excel 2016. Résultats : Pendant la période d'étude 2,46% des consultations ORL ont bénéficié d'une prise en charge chirurgicale pour goitre pluri-nodulaire bénin (19 cas/an) : 71 femmes (72,45%) et 27 hommes (27,55%), moyenne d'âge de 36 ans (17 à 44 ans). D'un point de vue socio-économique : 50 patients exerçaient une profession libérale et 35 patients étaient sans emploi fixe. Les motifs de consultation étaient une masse cervicale (67 patients), des signes d'hyperthyroïdie (20 patients) ou des signes de compression de l'axe viscéral du cou (11 patients). La durée moyenne avant consultation ORL était de 7,62 ans (1 à 18 ans). L'examen clinique avait objectivé une glande thyroïde "ferme" (70 patients ; 71,4%) pluri-nodulaire (76 patients ; 77,55%) sans adénopathie cervicale palpable (100%). Deux tiers des patients avaient un goitre de grade 3 de l'OMS. Les gestes chirurgicaux étaient une thyroïdectomie subtotale (52 ; 53,1%), une thyroïdectomie totale (30 patients ; 30,6%) et une lobectomie unilatérale avec isthmectomie (16 patients ; 16,3%). L'examen anatomo-pathologique a été réalisé pour toutes les pièces de thyroïdectomie objectivant un goitre macro-folliculaire chez 51 patients (52,04%). Aucun cas de décès n'a été enregistré. Les suites opératoires ont été marquées par un taux de paralysie récurrentielle de 2,78 % en termes de nerf à risque ainsi qu'une reprise chirurgicale pour drainage d'hématome compressif (2,04%). Conclusion : Le traitement de choix du goitre pluri-nodulaire bénin est théoriquement la thyroïdectomie totale. Cependant, le recours à une l'opothérapie et la nécessité d'un long suivi post-opératoire limite ses indications chez les patients de niveau socio-économique défavorable. Les techniques chirurgicales de thyroïdectomies partielles ou subtotales gardent tout leur intérêt dans ces indications

Critical appraisals and cultural acceptance of the dead donor rule: A revisit of the contemporary transplantation era

Transplantation remains one of the most rapidly expanding surgical specialties. Harvesting organs plays a crucial step in this highly complex surgical and communication process, and the moment at which vital organs can be donated depends on the declaration of end-of-life. This declaration must be performed by medical practitioners on the basis of clear standardized criteria of death confirmation, within competent local and regional jurisdictions, and with the use of confirmatory tests as indicated to ascertain the irreversibility of end-of-life. The current medically and legally accepted definition of death in most societies challenges the traditional and societal understandings of the process of end-of-life. Significant criticisms and cultural oppositions to transplantation still exist, and there is an ongoing debate about the role and the status of transplantation as surgical and medical sciences continue to evolve. By discussing the social acceptance and common understanding of end-of-life determination, we aim to highlight the current knowledge on transplant ethics with respect to the balance between the need to protect the potential organ donor and the need to donate organs at their utmost viability. No report has been done on social acceptance of transplantation in Rwanda or other Low- and Middle-Income countries (LMIC); though, as emphasis on organ transplantation evolves, we also aim to highlight the need for clear directions towards new transplantation regulations. Technical and non-technical critical arguments and moral acceptance are juxtaposed with the elucidated ethical and deontological principles to support the contemporary concept of the dead donor rule

Subjective voice assessment after thyroid surgery: a prospective study of 395 patients.

BACKGROUND: Total thyroidectomy has become a routine surgical procedure. However, postoperative complications are not rare and can lead to voice disorders. AIM: To study voice quality after total thyroidectomy. SETTINGS AND DESIGN: Prospective study over a period of 5 years in 395 surgical patients undergoing total thyroidectomy. MATERIALS AND METHODS: The voice quality of patients was based on systematic preoperative and postoperative laryngeal and voice examination. Voice assessment was performed by means of a voice quality questionnaire and recovery time within 12 months postoperatively. Patients who had inferior laryngeal nerve palsy were excluded from the study. RESULTS: Preoperative subjective voice disorders were found in 21% of patients and 49% had voice impairment after surgery. The recovery time was less than 1 month for one-half of the patients with impaired voices and 85% of the patients had recovered their voice after 5 months. At the 1-year postoperative examination, the permanent impaired voice rate was 1.26%. CONCLUSION: Voice impairment is common after thyroidectomy but usually transient and less than 20% persist at 6 months. Patients must be informed about the risk of voice impairment after thyroid surgery. An objective voice assessment is desirable to monitor the presence and progress of voice disorders.

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P> 0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, N G -nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect