Classifying Complications: Assessing Adult Spinal Deformity 2-Year Surgical Outcomes.

STUDY DESIGN: Retrospective review of prospective database. OBJECTIVE: Complication rates for adult spinal deformity (ASD) surgery vary widely because there is no accepted system for categorization. Our objective was to identify the impact of complication occurrence, minor-major complication, and Clavien-Dindo complication classification (Cc) on clinical variables and patient-reported outcomes. METHODS: Complications in surgical ASD patients with complete baseline and 2-year data were considered intraoperatively, perioperatively (\u3c6 \u3eweeks), and postoperatively (\u3e6 weeks). Primary outcome measures were complication timing and severity according to 3 scales: complication presence (yes/no), minor-major, and Cc score. Secondary outcomes were surgical outcomes (estimated blood loss [EBL], length of stay [LOS], reoperation) and health-related quality of life (HRQL) scores. Univariate analyses determined complication presence, type, and Cc grade impact on operative variables and on HRQL scores. RESULTS: Of 167 patients, 30.5% (n = 51) had intraoperative, 48.5% (n = 81) had perioperative, and 58.7% (n = 98) had postoperative complications. Major intraoperative complications were associated with increased EBL ( CONCLUSION: The Cc Scale was most useful in predicting changes in patient outcomes; at 2 years, patients with raised perioperative Cc scores and postoperative complications saw reduced HRQL improvement. Intraoperative and perioperative complications were associated with worse short-term surgical and inpatient outcomes

Limited morbidity and possible radiographic benefit of C2

Background: The study aims to evaluate differences in alignment and clinical outcomes between surgical cervical deformity (CD) patients with a subaxial upper-most instrumented vertebra (UIV) and patients with a UIV at C2. Use of CD-corrective instrumentation in the subaxial cervical spine is considered risky due to narrow subaxial pedicles and vertebral artery anatomy. While C2 fixation provides increased stability, the literature lacks guidelines indicating extension of CD-corrective fusion from the subaxial spine to C2. Methods: Included: operative CD patients with baseline (BL) and 1-year postop (1Y) radiographic data, cervical UIV ≥ C2. Patients were grouped by UIV: C2 or subaxial (C3-C7) and propensity score matched (PSM) for BL cSVA. Mean comparison tests assessed differences in BL and 1Y patient-related, radiographic, and surgical data between UIV groups, and BL-1Y changes in alignment and clinical outcomes. Results: Following PSM, 31 C2 UIV and 31 subaxial UIV patients undergoing CD-corrective surgery were included. Groups did not differ in BL comorbidity burden (P=0.175) or cSVA (P=0.401). C2 patients were older (64 Conclusions: C2 UIV patients showed similar cervical range of motion and baseline to 1-year functional outcomes as patients with a subaxial UIV. C2 UIV patients also showed greater baseline to 1-year horizontal gaze improvement and had complication profiles similar to subaxial UIV patients, demonstrating the radiographic benefit and minimal functional loss associated with extending fusion constructs to C2. In the treatment of adult cervical deformities, extension of the reconstruction construct to the axis may allow for certain clinical benefits with less morbidity than previously acknowledged

Cost-utility of revisions for cervical deformity correction warrants minimization of reoperations.

Background: Cervical deformity (CD) surgery has become increasingly more common and complex, which has also led to reoperations for complications such as distal junctional kyphosis (DJK). Cost-utility analysis has yet to be used to analyze CD revision surgery in relation to the cost-utility of primary CD surgeries. The aim of this study was to determine the cost-utility of revision surgery for CD correction. Methods: Retrospective review of a multicenter prospective CD database. CD was defined as at least one of the following: C2-C7 Cobb \u3e10°, cervical lordosis (CL) \u3e10°, cervical sagittal vertical axis (cSVA) \u3e4 cm, chin-brow vertical angle (CBVA) \u3e25°. Quality-adjusted life year (QALY) were calculated by EuroQol Five-Dimensions questionnaire (EQ-5D) and Neck Disability Index (NDI) mapped to SF-6D index and utilized a 3% discount rate to account for residual decline to life expectancy (men: 76.9 years, women: 81.6 years). Medicare reimbursement at 30 days assigned costs for index procedures (9+ level posterior fusion, 4-8 level posterior fusion with anterior fusion, 2-3 level posterior fusion with anterior fusion, 4-8 level anterior fusion) and revision fusions (2-3 level, 4-8 level, or 9+ level posterior refusion). Cost per QALY gained was calculated. Results: Eighty-nine CD patients were included (61.6 years, 65.2% female). CD correction for these patients involved a mean 7.7±3.7 levels fused, with 34% combined approach surgeries, 49% posterior-only and 17% anterior-only, 19.1% three-column osteotomy. Costs for index surgeries ranged from $20,001-55,205, with the average cost for this cohort of$44,318 and cost per QALY of $27,267. Eleven revision surgeries (mean levels fused 10.3) occurred up to 1-year, with an average cost of$41,510. Indications for revisions were DJK (5/11), neurologic impairment [4], infection [1], prominent/painful instrumentation [1]. Average QALYs gained was 1.62 per revision patient. Cost was $28,138 per QALY for reoperations. Conclusions: CD revisions had a cost of$28,138 per QALY, in addition to the $27,267 per QALY for primary CD surgeries. For primary CD patients, CD surgery has the potential to be cost effective, with the caveats that a patient livelihood extends long enough to have the benefits and durability of the surgery is maintained. Efforts in research and surgical technique development should emphasize minimization of reoperation causes just as DJK that significantly affect cost utility of these surgeries to bring cost-utility to an acceptable range

Epigenetic Regulation of Histone H3 Serine 10 Phosphorylation Status by HCF-1 Proteins in C. elegans and Mammalian Cells

BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein-DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12 degrees C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation

Mise en evidence et caractérisation d'une interaction fonctionnelle entre la kinase Aurora-A et la phosphatase PP2A

Mitosis progression is tightly controlled by a succession of enzymatic reactions, includingthose catalyzed by numerous protein kinases and phosphatases. More specifically, the mitoticserine/threonine kinase Aurora-A is required in these processes as it is involved in theregulation of the G2/M transition, centrosome cycle, mitotic spindle and chromosomessegregation. Aurora-A is activated by interacting with other proteins such as TPX2 or AJUBAand its kinase activity is modulated by the phosphorylation at specific sites. Besides, it hasbeen recently shown in vitro that Aurora-A degradation by the proteasome pathway isinduced by the dephosphorylation of a highly conserved residue: serine 51. In this study, wehave shown that the phosphatase PP2A and the kinase Aurora-A are co-localized incentrosomes and are interacting within the same complex. Moreover, the pharmacologicalinhibition of PP2A activity or the inhibition of its expression both led to Aurora-Astabilization in vivo. These results indicate that PP2A controls Aurora-A degradation in vivo.Finally, we confirmed in vivo in mammalian cells that phosphorylation of the S51 residueprevents the degradation of Aurora-A.Le déroulement de la mitose est très étroitement contrôlé par une succession de réactionsenzymatiques en particulier, celles catalysées par de nombreuses protéines kinases etphosphatases. Plus précisément, la sérine/thréonine kinase mitotique Aurora-A est essentielleà ces processus car elle participe à la régulation de la transition G2/M, du cycle descentrosomes, du fuseau mitotique et de la ségrégation des centrosomes. Aurora-A est activéegrâce à son interaction avec d'autres protéines telles que TPX2 et AJUBA et son activitékinase est modulée par la phosphorylation de sites spécifiques. Par ailleurs, il a été récemmentmontré in vitro que la dégradation de Aurora-A par la voie du protéasome est induite par ladéphosphorylation d'un résidu très conservé : la sérine 51. Ceci suggère qu'une phosphataseinduit la protéolyse de Aurora-A par déphosphorylation du résidu S51. Dans cette étude, nousavons montré que la phosphatase PP2A et la kinase Aurora-A sont co-localisées dans lescentrosomes des cellules mammifères et interagissent au sein d'un même complexe. De plus,l'inhibition pharmacologique de l'activité de PP2A ou l'inhibition de son expressionconduisent à stabiliser Aurora-A in vivo. Ces résultats indiquent que PP2A contrôle ladégradation de Aurora-A in vivo. Enfin, Nous avons confirmé in vivo dans des cellulesmammifères que la phosphorylation du résidu S51 protège Aurora-A de la dégradation

Mise en évidence et caractérisation d'une interaction fonctionnelle entre la kinase Aurora-A et la phosphatase PP2A

Le déroulement de la mitose est très étroitement contrôlé par une succession de réactions enzymatiques en particulier, celles catalysées par de nombreuses protéines kinases et phosphatases. Plus précisément, la sérine/thréonine kinase mitotique Aurora-A est essentielle à ces processus car elle participe à la régulation de la transition G2/M, du cycle des centrosomes, du fuseau mitotique et de la ségrégation des centrosomes. Aurora-A est activée grâce à son interaction avec d'autres protéines telles que TPX2 et AJUBA et son activité kinase est modulée par la phosphorylation de sites spécifiques. Par ailleurs, il a été récemment montré in vitro que la dégradation de Aurora-A par la voie du protéasome est induite par la déphosphorylation d'un résidu très conservé : la sérine 51. Ceci suggère qu'une phosphatase induit la protéolyse de Aurora-A par déphosphorylation du résidu S51. Dans cette étude, nous avons montré que la phosphatase PP2A et la kinase Aurora-A sont co-localisées dans les centrosomes des cellules mammifères et interagissent au sein d'un même complexe. De plus, l'inhibition pharmacologique de l'activité de PP2A ou l'inhibition de son expression conduisent à stabiliser Aurora-A in vivo. Ces résultats indiquent que PP2A contrôle la dégradation de Aurora-A in vivo. Enfin, Nous avons confirmé in vivo dans des cellules mammifères que la phosphorylation du résidu S51 protège Aurora-A de la dégradation.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Triple helix formation with Drosophila satellite repeats. Unexpected stabilization by copper ions.

International audienceThe Drosophila melanogaster (AAGAGAG)(n) satellite repeat represents up to 1.5% of the entire fly genome and may adopt non-B DNA structures such as pyrimidine triple helices. UV melting and electrophoretic mobility shift assay experiments were used to monitor the stability of intermolecular triple helices as a function of size, pH, and backbone or base modification. Three to four repeats of the heptanucleotide motif were sufficient to allow the formation of a stable complex, especially when modified TFOs were used. Unexpectedly, low concentrations (40-100 microM) of Cu(2+) were found to favor strongly pyrimidine triplex formation under near-physiological conditions. In contrast, a much higher magnesium concentration was required to stabilize these triplexes significantly, suggesting that copper may be an essential stabilizing factor for pyrimidine triplexes

Freedom and responsibility: Academic researchers’ public advocacy: COMETS - OPINION n°2023-44

Academic research staff have long been advocates of various causes in the public arena; researchers taking normative positions regarding various moral, political or social issues is nothing new. Today, however, given the many challenges facing our society, the question of public advocacy by researchers has taken on a new dimension. Many of them get involved to support causes or take a stance on societal issues - the fight against pandemics, environmental degradation, the rise of surveillance technologies, and so on. They do so in a variety of ways, from signing op-eds to contributing to the work of NGOs or think tanks, supporting legal action or writing blog posts. Moreover, the development of traditional and social media has significantly increased the public exposure of committed researchers. At the same time, many in the research community are questioning the modalities of such forms of engagement in the public sphere, its appropriateness and the very idea of it. They wonder whether and how to engage publicly without risking their reputation and the values shared by their research communities, without departing from the neutrality traditionally expected of researchers, and without jeopardising impartiality or credibility.The present opinion has been written with this context in mind. The result of a self-referral within COMETS, it aims to provide researchers with keys to understanding and ethical guidelines concerning public advocacy

Entre liberté et responsabilité : l’engagement public des chercheurs et chercheuses: AVIS n°2023-44

Que des personnels de recherche s’engagent publiquement en prenant position dans la sphèrepublique sur divers enjeux moraux, politiques ou sociaux ne constitue pas une réalité nouvelle.Aujourd’hui toutefois, face aux nombreux défis auxquels notre société est confrontée, la question del’engagement public des chercheurs s’est renouvelée. Nombre d’entre eux s’investissent pour soutenirdes causes ou prendre position sur des enjeux de société - lutte contre les pandémies, dégradation del’environnement, essor des technologies de surveillance, etc. – selon des modalités variées, de lasignature de tribunes à la contribution aux travaux d’ONG ou de think tanks en passant par le soutienà des actions en justice ou l’écriture de billets de blog. Par ailleurs, le développement des médias etdes réseaux sociaux a sensiblement renforcé l’exposition publique des chercheurs engagés.Dans le même temps, de forts questionnements s’expriment dans le monde de la recherche. Nombreuxsont ceux qui s’interrogent sur les modalités de l’engagement public, son opportunité et son principemême. Ils se demandent si et comment s’engager publiquement sans mettre en risque leur réputationet les valeurs partagées par leurs communautés de recherche, sans déroger à la neutralitétraditionnellement attendue des chercheurs, sans perdre en impartialité et en crédibilité. Ce débat, quianime de longue date les sciences sociales, irrigue désormais l’ensemble de la communautéscientifique.C’est dans ce contexte que s’inscrit le présent avis. Fruit d’une auto-saisine du COMETS, il entend fournir aux chercheurs des clés de compréhension et des repères éthiques concernant l’engagement public

Freedom and responsibility: Academic researchers’ public advocacy: COMETS - OPINION n°2023-44

Academic research staff have long been advocates of various causes in the public arena; researchers taking normative positions regarding various moral, political or social issues is nothing new. Today, however, given the many challenges facing our society, the question of public advocacy by researchers has taken on a new dimension. Many of them get involved to support causes or take a stance on societal issues - the fight against pandemics, environmental degradation, the rise of surveillance technologies, and so on. They do so in a variety of ways, from signing op-eds to contributing to the work of NGOs or think tanks, supporting legal action or writing blog posts. Moreover, the development of traditional and social media has significantly increased the public exposure of committed researchers. At the same time, many in the research community are questioning the modalities of such forms of engagement in the public sphere, its appropriateness and the very idea of it. They wonder whether and how to engage publicly without risking their reputation and the values shared by their research communities, without departing from the neutrality traditionally expected of researchers, and without jeopardising impartiality or credibility.The present opinion has been written with this context in mind. The result of a self-referral within COMETS, it aims to provide researchers with keys to understanding and ethical guidelines concerning public advocacy