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During mitosis, a functional spindle requires high microtubule turnover. Such turnover is highlighted by the multiple functions of spindle poles, where microtubule minus ends are concentrated, and where microtubule nucleation and depolymerization happen side by side. How these seemingly antagonistic processes are coordinated during poleward microtubule flux is not understood. Here we reconstitute this coordinationin vitrocombining different pole localized activities. We find that the spindle pole-localized kinesin-13 KIF2A is a microtubule minus-end depolymerase, in contrast to its paralog MCAK. Due to its asymmetric activity, KIF2A still allows microtubule nucleation by plus-end growth from the γ-tubulin ring complex (γTuRC), which in turn serves as a protective cap that shields the minus end against KIF2A binding. Efficient γTuRC-uncapping requires the combined action of KIF2A and a microtubule severing enzyme, then leading to treadmilling of the uncapped microtubule driven by KIF2A. Together these results provide insight into the molecular mechanisms by which a minimal protein module coordinates microtubule nucleation and depolymerization at spindle poles consistent with their role in poleward microtubule flux.

COG-UK is supported by funding from the MRC part of UK Research & Innovation, the National Institute of Health Research (Grant code MC_PC_19027), and Genome Research Limited, operating as the Welcome Sanger Institute. Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine. Publisher PDF

AimsThere is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C reactive protein (CRP), procalcitonin, mid-regional proadrenomedullin (MR-proADM) and white cell count to support prediction of clinical outcomes.Methods135 patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via reverse-transcription-qPCR were included. Biomarkers from within 24 hours of presentation were used to predict disease progression by Cox regression and area under the receiver operating characteristic curves. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, critical care admission and non-invasive ventilation (NIV) use.ResultsElevated MR-proADM was shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease, renal disease and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and NIV.ConclusionsThe measurement of MR-proADM and CRP in patients with confirmed COVID-19 infection on admission shows significant potential to support clinicians in identifying those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions.

UNSTRUCTURED Many Americans reference online reviews when selecting a physician [1,2]. In a 2014 report, 59% of individuals cited online patient ratings as an important factor in choosing a physician [1]. The widespread use and influence of these ratings raises questions about their potential impacts on healthcare delivery. Online reviews may have consequences for professional reputation and physician selection. There is value in discerning the factors that drive both positive and negative ratings, such that the former can be encouraged, and the latter minimized. Concerns have also been raised about how the setting of healthcare delivery (e.g., academic vs. private) and other systemic forces at play (e.g., gender and racial biases) could affect physicians’ online ratings [3]. Studies of online physician ratings have yielded clinically-relevant insights across a variety of medical specialties [3-6]. In ophthalmology, though, the factors driving online patient ratings remain largely unclear. In the present study, we evaluate whether certain ophthalmologist- and practice-related factors influence patient satisfaction, as reported in online ratings. Methods We analyzed Yelp reviews of ophthalmology practices (from 2013−2020) located in New York City, New York (n=150). Patient reviews were coded for overall rating, as either “low” (1- or 2-star) or “high” (4- or 5-star). Then, binary logistic regression was used to determine whether certain physician and practice-related factors increased the likelihood of receiving low versus high ratings. Results When patients knew the name of their treating ophthalmologist, online ratings were more likely to be high than low (OR=5.57; P=.01). Ophthalmology practices were more likely to respond to reviews after receiving low ratings (OR=0.238; P=.04). Interestingly, ratings were not associated with physician race, physician gender, practice type (academic vs. private), or the number of practice physicians. Discussion Patients were more likely to post high ratings when they knew the name of their treating ophthalmologist. A plausible rationale may be that patients are more likely to remember an ophthalmologist’s name when a warm introduction is made and a personal connection is felt. This finding is consistent with similar studies in other specialties that found ratings were influenced by physicians’ bedside manner and communication style [4-6]. Unlike previous studies, online ratings of ophthalmologists did not show associations with practice type (academic vs. private), physician race, or physician gender [3]. These cross-specialty differences raise interesting questions about how systemic influences may manifest differently across various care settings. Though, it’s also important to acknowledge this study’s narrow sampling scope, as findings may vary for practices in different communities and geographic regions. Ophthalmology practices that received lower ratings were more likely to respond to reviews. These findings suggest that practices appreciate the influence of online ratings, and may be concerned by how low ratings could hurt practice reputation or dissuade future patients. To mitigate potential harm, ophthalmologists may feel incentive to provide context or a thoughtful response to negative online reviews. We relay this exploratory data in the spirit of cultivating interest and generating hypotheses. Given the increasing influence of online patient reviews, further study is encouraged to clarify the driving factors behind high ratings, and to develop strategies to respond effectively to low ratings.

Background: Despite heightened interest in early-onset CRC, little is known about the tumor molecular, immune, and microbial characteristics of early-onset CRC. It is also unclear whether CRCs diagnosed at or shortly after age 50 are similar to early-onset CRC. We hypothesized that tumor molecular, immune, and microbial characteristics in CRC tissue might show differential heterogeneity patterns between three age groups ( Methods: We examined 3,395 CRC cases with available tissue data, including 660 early-onset and 243 intermediate-onset cases in the Nurses' Health Study, Health Professionals Follow-up Study, and Ontario Familial Colon Cancer Registry. We profiled the in situ T-cell landscape of 959 cases using digital imaging, machine learning, and a customized 9-plex multiplexed immunofluoresence panel with antibodies directed against CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, and MKI67 (Ki-67). Using chi-squared test or Spearman’s correlation test, we assessed differences in tumor characteristics including microsatellite instability, CpG island methylator phenotype (CIMP), KRAS, and BRAF mutations, LINE-1 methylation levels, pks+ E. coli and Fusobacterium nucleatum positivity, histopathologic lymphocytic reaction, and T-cell densities between early-onset, intermediate-onset, and later-onset cases. Results: Compared to later-onset CRC (21%), early-onset (4.8%) and intermediate-onset CRCs (5.1%) exhibited a lower prevalence of CIMP-high status (P Conclusions: Compared to later-onset CRC, early-onset and intermediate-onset CRCs tended to have aggressive tumor phenotypes such as LINE-1 hypomethylation, lower lymphocytic immune reaction, and a higher density of MKI67+ immune cells. These findings highlight the importance of the tumor microenvironment in the etiology of early-onset and intermediate-onset CRCs. Citation Format: Tomotaka Ugai, Yasutoshi Takashima, Andressa Dias Costa, Daniel Buchanan, Jeroen Huyghe, Li Hsu, Conghui Qu, Claire Thomas, Steve Gallinger, Robert Grant, Ulrike Peters, Amanda I. Phipps, Jonathan Nowak, Shuji Ogino. Molecular, immune, and microbial profiles of early-onset, intermediate-onset, and later-onset CRCs. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5760.

Background. Prior studies have demonstrated that the overall density of T cells in colorectal tumors is favorably associated with colorectal cancer (CRC) survival; however, few studies have considered the potentially distinct roles of heterogeneous T cell subsets in different tissue regions in relation to CRC outcomes. Methods. We used data and colorectal tumor specimens from a subset of participants in three studies (total N=878). We profiled the in situ T cell landscape of CRC using digital imaging, machine learning, and a customized 9-plex multiplexed immunofluoresence panel with antibodies directed against CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, and MKI67. This allowed us to determine the density of T cell subsets defined according to marker co-localization and according to tissue region (i.e., epithelial, stromal). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of T cell subset densities in CRC with disease-specific survival, adjusting for age, sex, tumor site, microsatellite instability status, CpG island methylator phenotype status, status of somatic mutations in BRAF and KRAS, stage, and study. Results. Overall, the densities of CD3+CD4+ helper T cells and CD3+CD8+ cytotoxic T cells in CRC were favorably associated with CRC-specific survival. However, in analyses stratified by tissue region, the association of CD3+CD4+ helper T cell density with survival was limited to density in stromal regions (HR for highest vs. lowest density quartile=0.40, 95% CI: 0.26-0.63, ptrend Conclusions. The density of T cells in CRC tissue is significantly associated with CRC survival, independent of stage at diagnosis and other evaluated tumor markers; however, the T cell subsets that are associated with CRC outcomes differ according to tissue region. These findings highlight the differing roles of distinct T cell subsets in CRC with regard to cancer outcomes, and support the need for additional work identifying factors that contribute to T cell response profiles in CRC. Citation Format: Amanda I. Phipps, Jonathan Nowak, Yasutoshi Takashima, Daniel Buchanan, Andressa Dias Costa, Steven Gallinger, Jeroen Huyghe, Li Hsu, Conghui Qu, Claire Thomas, Sushma Thomas, Tomotaka Ugai, Ulrike Peters, Shuji Ogino. Density of T cell subsets in colorectal cancer in relation to disease-specific survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3019.

ImportanceMany conventional end points in randomized clinical trials of interventions for critically ill patients do not account for patient-centered concerns such as time at home, physical function, and quality of life after critical illness.ObjectiveTo establish whether days alive and at home at day 90 (DAAH90) is associated with long-term survival and functional outcomes in mechanically ventilated patients.Design, Setting, and ParticipantsThe RECOVER prospective cohort study was conducted from February 2007 to March 2014, using data from 10 intensive care units (ICUs) in Canada. Patients were included in the baseline cohort if they were aged 16 years or older and underwent invasive mechanical ventilation for 7 or more days. The follow-up cohort analyzed here comprised RECOVER patients who were alive and had functional outcomes ascertained at 3, 6, and 12 months. Secondary data analysis occurred from July 2021 to August 2022.ExposuresComposite of survival and days alive and at home at day 90 after ICU admission (DAAH90).Main Outcomes and MeasuresFunctional outcomes at 3, 6, and 12 months were evaluated with the Functional Independence Measure (FIM), the 6-Minute Walk Test (6MWT), the Medical Research Council (MRC) Scale for Muscle Strength, and the 36-Item Short Form Health Survey physical component summary (SF-36 PCS). Mortality was evaluated at 1 year from ICU admission. Ordinal logistic regression was used to describe the association between DAAH90 tertiles and outcomes. Cox proportional hazards regression models were used to examine the independent association of DAAH90 tertiles with mortality.ResultsThe baseline cohort comprised 463 patients. Their median age was 58 years (IQR, 47-68 years), and 278 patients (60.0%) were men. In these patients, Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, ICU intervention (eg, kidney replacement therapy or tracheostomy), and ICU length of stay were independently associated with lower DAAH90. The follow-up cohort comprised 292 patients. Their median age was 57 years (IQR, 46-65 years), and 169 patients (57.9%) were men. Among patients who survived to day 90, lower DAAH90 was associated with higher mortality at 1 year after ICU admission (tertile 1 vs tertile 3: adjusted hazard ratio [HR], 0.18 [95% CI, 0.07-0.43]; P 90 was independently associated with lower median scores on the FIM (tertile 1 vs tertile 3, 76 [IQR, 46.2-101] vs 121 [IQR, 112-124.2]; P = .04), 6MWT (tertile 1 vs tertile 3, 98 [IQR, 0-239] vs 402 [IQR, 300-494]; P P P = .001) measures. Among patients who survived to 12 months, being in tertile 3 vs tertile 1 for DAAH90 was associated with higher FIM score at 12 months (estimate, 22.4 [95% CI, 14.8-30.0]; P P = .15) or ICU-free days (estimate, 5.9 [95% CI, −2.1 to 13.8]; P = .15) at day 28.Conclusions and RelevanceIn this study, lower DAAH90 was associated with greater long-term mortality risk and worse functional outcomes among patients who survived to day 90. These findings suggest that the DAAH90 end point reflects long-term functional status better than standard clinical end points in ICU studies and may serve as a patient-centered end point in future clinical trials.

Claire Thomas explores how her practice has fared regarding low-carbon design solutions, and asks what the construction industry can do to encourage low-carbon outcomes.

Simulated learning activities are an effective tool for reducing speech-language therapy (SLT) students' anxiety and improving their confidence for clinical placements. Such activities include interacting with patients who are actors, clinical educators or peers and are known to decrease anxiety and increase confidence in SLT students. Screen-simulated patients using video are another alternative, which has not yet been fully evaluated in the education of SLT students.To compare the effectiveness of (1) modified simulated patient and (2) video simulated learning for increasing self-reported (a) confidence and (b) preparedness and (c) decreasing self-reported anxiety.This study used a randomized crossover design with 127 first-year graduate-entry master's SLT student participants. Students participated in two activities related to a clinical interaction with a paediatric client's carer: (1) a 1-hr modified simulated patient experience with clinical staff as the simulated patient; and (2) a video-learning task, with two videos of a clinician-carer interaction and an accompanying worksheet. Students were randomly allocated to a group of four students and the groups randomly allocated to receive modified simulated patient or video-learning first. Students were not blinded to the activities. The students completed a 19-item questionnaire at three time points: before either activity, after the first activity and after the second activity, to evaluate their self-reported confidence, clinical preparedness and anxiety.A total of 62 students completed modified simulated patient first and 63 completed video-learning first. After either single activity the students had significantly increased confidence and preparedness scores, while only the modified simulated patient significantly reduced student anxiety scores. As a second activity, modified simulated patient resulted in further significant improvements in confidence, preparedness and anxiety; however, adding video learning as a second activity resulted in no significant benefit.This study demonstrates the effectiveness of two low-resource clinical-learning activities for novice SLT students that can be applied in a range of settings. Of the two activities, modified simulated patient had greater effectiveness, as it was the only activity to decrease anxiety. An investigation of the pedagogical principles within the activities revealed that modified simulated patient activity had more opportunities for peer learning, supervisor feedback and verbal reflection in comparison with video learning that may explain the increased benefits.What is already known on the subject Simulated learning activities are an effective teaching tool for SLT students, increasing confidence and decreasing anxiety in preparation for placement. Simulated patients require more resources than video simulation. Both simulated patients and video simulation provide a safe learning environment, where students can learn without risk to clients. What this paper adds to existing knowledge This study is among the first to investigate a modified version of simulated patients; our modification involves a clinical educator performing the role of both the simulated patient and simulation facilitator. It is the first to evaluate simulation via video learning for SLT students. The paper demonstrates the effectiveness of these two activities, and the slight advantage of modified simulated patient, for increasing novice students' confidence and preparedness and decreasing their anxiety about clinic. It also unpacks the pedagogical principles used in each activity to explain the reasons that modified simulated patient had greater effectiveness. What are the potential or actual clinical implications of this work? The two educational activities required no specialist equipment and can be applied in a range of pre-clinical and clinical settings by university staff and/or community clinical educators. Increasing confidence and preparedness, and decreasing anxiety will help ensure that student learning on scarce clinical placements is maximized.

Purpose: The aim of this study was to investigate the time course of maximal isometric finger flexor force and blood acid–base balance during repeated simulated matches in world-class judokas. Methods: Seven 21- to 28-year-old world-class female judokas (including Olympic and World Championship medalists) repeated four 4-minute judo combats interspersed by 15 minutes of passive recovery. Maximal voluntary isometric finger flexor contraction (MVIC) force was measured in both hands after warm-up and immediately after each combat using a handgrip dynamometer. MVIC force was classified as MVIC hikite force (pulling hand) and MVIC tsurite force (lifting hand). Results: Blood lactate concentration, pH, bicarbonate concentration, partial pressure of oxygen, and oxygen saturation were measured between 3 and 5 minutes after each match. At completion of the fourth combat, mean MVIC hikite and tsurite force decreased by 18% and 12%, respectively (g = 0.23 and 0.29, respectively; P −1 after warm-up to 13.10 (2.61) mmol·L−1 after the last match (g = 4.13, P = .018). Concurrently, blood pH decreased slightly from 7.44 (0.03) to 7.26 (0.05) (g = 2.34, P = .018), that is, by only 0.18 units. The decreased blood pH was significantly correlated with a decrease in bicarbonate concentration (R2 = .94, P Conclusions: Female world-class judokas were able to maintain a high level of grip strength in both hands and efficiently regulate blood acid–base balance during repeated simulated high-intensity matches.

Introduction. The closed-loop (BF) insulin therapy system is a medical device that automates the delivery of insulin based on blood sugar levels, like the native pancreas. While current BF devices control glycemia very well at night and at fasting state, they remain in trouble in controlling such disruptive elements as diet and physical activity (PA), and these must be declared in advance (hybrid CL). Although the management of meals is well advanced, many aspects related to PA remain to be studied in depth. Regular PA is beneficial for patients with type 1 diabetes (T1D), as it reduces their cardiovascular risk, improves their overall glycemic control (reduction of HbA1c and insulin requirements), and improves their mental state. However, the fear of hypoglycemia is a major obstacle that limits their practice of PA. Objectives. The objectives of this work are threefold: (i) to demonstrate the efficacy and tolerability of the CL insulin therapy system (DBLG1) for glycemic control in patients with T1D, (ii) to evaluate the efficacy of the DBLG1 system for the prevention of PA-induced hypoglycemia, and (iii) to determine the factors that explain the possible therapeutic efficacy of the DBLG1. Personal Contribution. Two real-life studies have demonstrated that the DBLG1 system significantly increases time spent in glycemic target compared to standard (open-loop) therapy. Two other real-life studies have evidenced the reduction of the incidence of hypoglycemia linked to PA by the DBLG1 system. Adjustments of insulin doses and the recommendation of a preventive intake of carbohydrates probably explain this therapeutic benefit. Closed-loop limitations. Although automated, hybrid CL insulin therapy systems still require the user to declare the carbohydrate content of their meals and their AP to efficiently adjust insulin delivery. Perspectives. Several works in progress are devoted to the development of fully automated CL systems with the detection and management of PA and meals. Conclusions. The new CL insulin therapy DBLG1 system significantly reduces PA-induced hypoglycemia by adjusting insulin delivery and recommending preventive carbohydrate intake., Introduction. Le système d’insulinothérapie en boucle fermée (BF) est un dispositif médical qui automatise l’administration d'insuline en fonction de la glycémie, à l’image du pancréas humain. Si les dispositifs actuels de BF contrôlent très bien la glycémie la nuit et à jeun, ils restent en difficulté pour contrôler les éléments perturbateurs que sont l’alimentation et l’activité physique (AP), et ceux-ci doivent être déclarés de façon anticipée (BF hybride). Si la gestion des repas est bien avancée, beaucoup d’aspects liés à l’AP restent à approfondir. L'AP régulière est bénéfique pour les patients atteints de diabète de type 1 (DT1), car elle réduit leur risque cardiovasculaire, améliore globalement leur contrôle glycémique (réduction de HbA1c et des besoins en insuline), et améliore leur bien-être. Cependant, la peur de l'hypoglycémie est un obstacle majeur qui limite leur pratique d’AP. Objectifs. Ce travail poursuit un triple objectif : (i) démontrer l’efficacité et la tolérance du système d’insulinothérapie en BF DBLG1 pour assurer le contrôle glycémique du sujet atteint de DT1, (ii) évaluer l’efficacité de ce système pour prévenir les hypoglycémies induites par l'AP, et (iii) déterminer les facteurs explicatifs d’une éventuelle efficacité thérapeutique. Contribution personnelle. Deux études en conditions de vie réelle ont démontré que le système d'insulinothérapie en BF DBLG1 augmente significativement le temps dans la cible glycémique par rapport à la thérapie standard (boucle ouverte). Deux autres études en vie réelle ont montré la réduction de l’incidence des hypoglycémies liées à l’AP par le système DBLG1. Des ajustements des doses d'insuline et la recommandation d'un apport préventif en glucides expliquent probablement ce bénéfice thérapeutique. Limitations de la BF. Bien qu’automatisés, les systèmes d'insulinothérapie en BF nécessitent encore que l'utilisateur déclare la teneur en glucides de ses repas et son AP pour ajuster efficacement l’administration d'insuline. Perspectives. Plusieurs travaux en cours sont consacrés au développement de systèmes en BF implémentant détection et gestion entièrement automatisées de l’AP et des repas. Conclusions. Le nouveau système d'insulinothérapie en BF DBLG1 réduit notablement l'hypoglycémie induite par l'AP, en ajustant l'administration d’insuline et en recommandant un apport préventif en glucides.

It has previously been observed in humans that rapid normalization of hyperglycemia can cause a neuropathy called Treatment-Induced Neuropathy in Diabetes (TIND), which affects small peripheral fibers. The pathophysiology of this phenomenon is not clear, but we observe the presence of hypervascularization and inflammation in contact with the nerve endings, with opening of the arteriovenous shunt simultaneous with the symptoms. On another note, in patients living with diabetes, the development of a rare and devastating joint complication called Charcot's neuroarthropathy (CN) has been observed. The pathophysiology of CN is not completely known, but there is an activation of markers of inflammation and bone remodeling. Inflammation and peripheral hypervascularization therefore seem to be a common link between the two pathologies mentioned (TIND and CN). We have confirmation that the rapid correction of chronic hyperglycemia can trigger (not systematically) an TIND, but what about the influence of this rapid correction on the appearance of a CN in patients with a plan for a correction? rapid unbalanced diabetes The objective of this thesis is to assess whether the rapid reduction in HbA1c can accompany the onset of an active phase of CN. During the work, clinical evaluations, observational studies and interventional actions were carried out on patients living with diabetes complicated by an active phase of NC. They demonstrated that a rapid reduction in the threshold of HbA1c appears to be an element associated with the onset of an active phase of CN. As in the onset of TIND, the rapid reduction in the threshold of HbA1c appears to be a contributing factor in the onset of CN.; Il a déjà été observé chez l’homme que la normalisation rapide d’une hyperglycémie peut provoquer une neuropathie nommée « la neuropathie induite par le traitement du diabète (NITD) », qui touche les petites fibres périphériques. La physiopathologie de ce phénomène n’est pas claire, mais on observe la présence d’une hypervascularisation et d’une inflammation au contact des extrémités nerveuses, avec ouverture de shunt artérioveineux simultanée aux symptômes. Dans un autre registre, chez les patients vivant avec un diabète, l’apparition d’une complication rare et dévastatrice pour les articulations nommée la neuroarthropathie dite « de Charcot (CN) » a été observée. La physiopathologie de la CN n’est pas complément connue, mais on note une activation des marqueurs d’inflammation et du remodelage osseux. L’inflammation et l’hypervascularisation périphérique semblent donc être un lien commun entre les deux pathologies citées (la NITD et la CN). Nous avons la confirmation que la correction rapide d’une hyperglycémie chronique peut déclencher (pas systématiquement) une NITD. Qu’en est-il de l’influence de cette correction rapide sur l’apparition d’une CN chez les patients avec un projet de correction rapide d’un diabète déséquilibré ? L’objectif de cette thèse est donc d’évaluer si la réduction rapide de l’HbA1c peut accompagner l’apparition d’une phase active de la CN. Au cours de ce travail de thèse, des évaluations cliniques, des études observationnelles et des actions interventionnelles ont été réalisées auprès de patients vivant avec un diabète compliqué par une phase active de la CN. Ils ont démontré qu’une réduction rapide de seuil de l’HbA1c semble être un élément associé à l’apparition d’une phase active de la CN. Comme pour l’apparition de la NITD, la réduction rapide de seuil de l’HbA1c semble être un élément participant à l’apparition de la CN.