Roger Erivan
email: rerivan@chu-clermontferrand.fr

Julien Dartus

Guillaume Villatte

Pierre Sylvain

Stéphane Descamps

Stéphane Boisgard

Bibliometric analysis of case report citations and their effect on the impact factor: How does publishing case reports impact journals?

Keywords: IV, systematic retrospective study bibliometric, Case report, Publication rate, orthopedics, impact factor

Given their low citation rate, case reports may reduce a journal's impact factor (IF), making a journal less likely to accept them for publication. However, this concept has never been proven in a bibliometric study. This led us to carry out a bibliometric analysis to evaluate 1) the exact number of case reports published in orthopedics over a 2-year period, 2) their citation rate, 3) what the journals' IF would be if they had not published these case reports.

Hypothesis:

Publishing case reports reduces a journal's IF, bringing into question whether they should be published.

case reports since they can be useful to clinicians caring for patients with rare diseases or medical conditions.

Materials and Methods

This was a retrospective bibliometric study. We focused on all the articles influencing the year 2017.

We looked at all the journals in the "Orthopedics" discipline that had published at least one article in the years N-2 (= 2015) or N-1 (= 2016).

Results:

There were 1925 case reports among the 28,903 articles published in all orthopedics journals in 2015-2016, a 6.7% share of publications. Individually, each case report in 2015-2016 was cited an average of 0.86 times ± 1.4 [0-13] in 2017. Of all the case reports published in 2015-2016, 571 (30%) had not been cited in 2017. When comparing the individual number of each case report citation to the journal's IF, we found 413 instances (21.5%) where the case report was cited more than expected and 1512 (78.5%) where it was cited less than expected based on the journal's IF. The mean IF was 2.013. If the journals had not published any case reports, the mean IF would have been 2.072 (p < 0.0001). For all the SIGAPS categories, the mean IF would have been higher if no case reports had been published. On average, the IF was lower by 0.059 points ± 0.121 [-0.165 -0.537], with the difference being statistically significantly only for SIGAPS C and D journals. In 69 instances, the IF would be higher if the journal had not published any case reports. Conversely, the IF improved in 8 instances by publishing case reports: 3 were tier D journals and 5 were tier E journals.

Discussion:

Our study brings into question whether case reports should be published. Indeed, the publication of case reports lowers the IF of scientific journals. However, we should not completely stop publishing

Introduction

Scientific publications are a medium to communicate and exchange scientific knowledge. It is used extensively, especially in orthopedics, and the research domains are broad [START_REF] Dartus | Bibliometric evaluation of orthopaedics and traumatology publications from France: 20-year trends (1998-2017) and international positioning[END_REF][START_REF] Saab | Publication output of French orthopedic and trauma surgeons: Quantitative and qualitative bibliometric analysis of their scientific production in orthopedics and other medical fields[END_REF][START_REF] Ollivier | Disrupting research in orthopedics: Reasons for facing the challenge of change[END_REF]. Among the millions of scientific publications throughout the world, few will ever be heavily cited [START_REF] Van Noorden | The top 100 papers[END_REF]. Scientific journals publish articles to disseminate scientific information in their domains. A journal's impact factor (IF) evaluates its publication rate and citation rate by taking the ratio between the number of times a published article is cited in the 2 years before the analysis and the number of articles published during these same 2 years. While optimizing the IF has positive effects such as having journals compete and helping to rank researchers, it has its drawbacks, since some journals focus narrowly on increasing their IF. While some question whether the IF is still a useful concept, it continues to be used to compare journals to each other [START_REF] De Barros | Relation between impact factor in orthopedic journals and level of evidence[END_REF][START_REF] Giebaly | Getting Research Published and Achieving the Highest Impact Factor[END_REF][START_REF] Kodumuri | The impact factor of a journal is a poor measure of the clinical relevance of its papers[END_REF][START_REF] Haddad | The impact factor: yesterday's metric?[END_REF][START_REF] Erivan | The top 100 most-cited Orthopaedics & Traumatology: Surgery & Research articles[END_REF].

Various types of scientific studies can be done depending on the type of pathology, its frequency and whether or not patients can be enrolled in prospective studies. These studies have different levels of evidence, ranging from meta-analyses of randomized trials (highest level) to case-control studies, retrospective studies and lastly, case reports (CR). An investigator aims for the highest level of evidence possible. However, certain disease conditions are rare and can only be documented by publishing a CR about isolated cases. The same goes for complications, novel treatment of a known disease or new conditions. These articles are useful for fewer readers than a study on a more widespread medical condition. Given the low citation rate of CRs [START_REF] Edelmayer | Case report classics in otolaryngology -head and neck surgery: citation analysis[END_REF], they are said to contribute to decreasing the IF of scientific journals, making it harder and harder for them to get accepted for publication [START_REF] Malatack | The Case for the Case Report[END_REF]. CRs are less desirable to journals that are focused on increasing their IF. However, their true influence on bibliometric data has not been described accurately. This led us to carry out a bibliometric study to evaluate 1) the exact number of case reports published in orthopedics over a 2year period, 2) their citation rate, 3) what the journals' IF would be if they had not published these case reports. We hypothesized that publishing case reports reduces a journal's IF, bringing into question whether they should be published.

Materials and methods

Materials

This was a bibliometric study. We looked at all the articles influencing the year 2017 (the last year with IF data available when we carried out this study). The 2017 IF was calculated by dividing the number of 2017 citations of articles published in 2015 and 2016 by the number of articles published in 2015 and 2016. The IF data was taken from SIGAPS (software to identify, manage and analyze scientific publications). The SIGAPS classification helps to make the various disciplines more comparable and is used to rank journals based on their IF [START_REF] Yuen | Comparison of Impact Factor, Eigenfactor Metrics, and SCImago Journal Rank Indicator and h-index for Neurosurgical and Spinal Surgical Journals[END_REF].

Methods

We looked at all the journals in the "Orthopedics" discipline that had published at least one article in the years N-2 (= 2015) or N-1 (= 2016). We included all the CRs in the year of interest through a manual search and then analyzed each article by its title and/or abstract. Case series were excluded so as to focus solely on CRs, which are articles featuring a single patient. We did this because the definition of a CR varies between journals and there is no threshold for when a case series becomes a retrospective study. For each journal, we used PubMed and Google Scholar to determine how many articles had been published in this journal in years N-2 and N-1 of the 2017 IF, then we looked at all the CRs published in each journal in years N-2 and N-1. For each CR, we used Google Scholar to determine how many times this article had been cited in 2017, thereby affecting the IF. With these data, we determined the mean number of true citations that we then compared to the expected number of citations for each article based on the journal's IF and its number of publications. The number of citations expected in 2017 for each article published in 2015 and 2016 is equal to the journal's 2017 IF. We determined how many times each CR was cited more or less than the expected number of citations based on the journal's IF. We then looked at what the journals' IF would be if they had not published these CRs by counting how many articles were not CRs and how often they were cited.

Statistics

Statistical calculations were done using Excel™ software (Microsoft, Redmond, USA) and Addinsoft (2019) XLSTAT™ statistical and data analysis solution (Long Island, NY, USA). The findings were summarized with mean ± standard deviation, minimum and maximum values for quantitative variables or with median and quartiles for data that was not distributed normally. The normality of the distributions was verified using the Shapiro & Wilk test; with normal data, the significance of differences between means was tested using Student's t test; otherwise the nonparametric Wilcoxon test was used. Counts were compared using Fischer's exact test or the Chi-square test as appropriate.

Correlations were calculated with Pearson's coefficient. There was no missing data; all the abstracts were analyzed. The risk of a Type I error was set 5% and 95% confidence intervals were used.

Results

In the year 2017, we identified 79 journals in the Orthopedics category, of which two were excluded because they did not publish articles in the years N-2 and N-1 (Isokinet Exerc Sci and J Am Podiatry Assoc). A list of the journals included with their IF and SIGAPS tier is provided in Appendix 1. where the case report was cited more than expected and 1512 (78.5%) where it was cited less than expected based on the journal's IF. There was a weak but significant correlation between the journal's IF and the number of CR citations (Pearson 0.048, p = 0.034). Articles ranked as "SIGAPS A" were cited 1.93 times ± 3.28 [0-12], more than average relative to the articles in the other SIGAPS categories (p = 0.003). Articles classified as "SIGAPS B" were cited an average of 0.98 times ± 1.41 [0-7] relative to articles in the other SIGAPS categories (p = 0.29). Articles classified as "SIGAPS C" were cited an average of 0.76 times ± 1.22 [0-9] relative to articles in the other SIGAPS categories (p = 0.07). Articles classified as "SIGAPS D" were cited 0.99 times ± 1.53 [0-13], more than average relative to the articles in the other SIGAPS categories (p = 0.00008). Articles classified as "SIGAPS E" were cited 0.54 times ± 0.98 [0-6], less than average relative to the articles in the other SIGAPS categories (p = 0.000004).

The study flow chart is shown in

The mean IF of journals relative to the SIGAPS rank of their journal and their estimated IF without the

CRs is shown in Table 2. The mean IF was 2.013. If the journals had not published any case reports, the mean IF would have been 2.072 (p < 0.0001). For all the SIGAPS categories, the mean IF would have been higher if no CRs had been published, with the difference being statistically significantly only for the SIGAPS C and D journals. On average, the IF was lower by 0.059 points ± 0.121 [-0.165 -0.537]. In 69 instances, the IF would have increased if the journal had not published any case reports.

Conversely, the IF improved in 8 instances by publishing case reports: 3 were D journals and 5 were E journals.

Discussion

Our study found a considerable number of CRs being published in orthopedics. However, their citation rate was lower than expected given the journals' IF. The fact that journals published CRs lowered their IF in most instances, confirming our hypothesis. The advantage of publishing this type of research appears small if we solely look at the IF and citation rate. Nevertheless, more than 20% of the CRs were cited more than expected. The IF differences in our study were small. This is in large part because CRs made up only a small share of the total number of articles published that influence the journals' IF. While the difference in IF with and without CRs is small, the probability was very high because of the large number of articles analyzed (nearly 2000).

Many novel findings came out of our study, including the large number of CRs where the real citation rate was lower than the expected rate. While letters to the editor have previously raised questions about whether CRs should be published at all, no statistical analysis has been done up to now to support these statements [START_REF] Mason | The case report--an endangered species?[END_REF][START_REF] Ruano-Ravina | Regarding a case report: Rare diseases and bibliometric impact factor[END_REF][START_REF] Roos | Let's hear it for the case report[END_REF]. An article's citation rate is important because it reflects on its scientific reach. CRs are often read by a surgeon on a case-by-case basis without being used or cited in another article. Clinicians who are faced with a rare but tangible condition often look at case reports. Thus the usefulness of a CR goes beyond being cited; it helps in treating patients with complex or rare medical conditions [START_REF] Firat | Case reports: Should we do away with them?[END_REF]. CRs have a teaching aspect to them, also making them useful in this manner.

Citations of CRs in the journals with the highest IF (SIGAPS A) were the most common. Conversely, CRs were less cited in lower-tier journals (SIGAPS E). Paradoxically, CR in class D journals were cited more than the other CRs. Nevertheless, this higher rate still contributed to these journals having a lower IF. We can hypothesize that publishing few CRs explains the impact on the IF. In fact, we observed a paradoxical effect in certain journals that published many CRs and were affected in the inverse direction to other journals.

While bibliometric studies such as this one are becoming more common, they have limitations [START_REF] Ollivier | Disrupting research in orthopedics: Reasons for facing the challenge of change[END_REF].

1) The first limitation is that we only looked at 1 year. Nevertheless, we had a large number of articles, which led to us finding significant differences in the main outcome measure. A major problem with analyzing 2 years would have been taking into account how each journal's IF changes, and especially since certain journals shift from one SIGAPS category to another from one year to the next.

2) The data extraction was done by two of the authors; however, this search was likely not exhaustive and may have missed some articles.

3) We did not include articles that had "case report" in their title but described several cases so as to be more restrictive; in all reality, these articles likely had a higher chance of being cited. 4) This study was retrospective, as any bibliometric analysis would be. 5) Certain journals refuse to consider CRs, which may be a selection bias, although in our analysis, every journal had at least one published CR, even those that typically refuse them. 6) We used the SIGAPS classification in our analysis, although the ranking of the journals provided by this classification is not perfect. This problem often occurs with journals classified in different categories based on their target specialty: orthopedics, surgery, etc. Despite these limitations, our original study casts doubt on whether it is useful to publish CRs from a purely bibliometric viewpoint.

A long-term analysis would be needed to verify these conclusions and to see if the observed effects increase or decrease over time.

Conclusion

Our study brings into question whether case reports should be published. Indeed, the publication of case reports lowers the IF of scientific journals. However, we should not completely stop publishing case reports since they can be useful to clinicians caring for patients with rare diseases or medical conditions.

Figure 1 .

 1 There were 990 CRs published in 2015 and 935 in 2016, for a total of 1925 CRs in the years 2015 and 2016. On average, the journals had published 12.9 CRs ± 20.4 [0-91] in 2015 and 12.1 CRs ± 20.6 [0-113] in 2016.Since these journals published 28,903 articles in all of 2015 and 2016, CRs made up 6.7% of these publications (Table1). On average, each journal had published 192.1 ± 164.0 [0-644] articles in 2015 and 191.1 ± 148.9 [0-588] in 2016. There was a negative but non-significant correlation (-0.159; p = 0.167) between a journal's IF and the number of CRs published. Individually, each CR was cited an average of 0.86 times ± 1.4 [0-13] in 2017. CRs published in 2015 had a mean of 0.96 ± 1.49 [0-13] citations, while those published in 2016 had a mean of 0.76 ± 1.29 [0-13] citations (p = 0.002). Of all the CRs, 571 (30%) were not cited at all in 2017. When comparing the individual number of each case report citation to the journal's IF, we found 413 instances (21.5%)

Figure 1 :

 1 Figure 1: Flow chart (only the articles featuring a single patient were retained as a case report; those

Table 1 :

 1 Analysis of case reports published in 2015 and 2016 with the number of citations in 2017

	SIGAPS	Number of	Number of case	Total number	% case reports	Number of case
	tier	journals	reports	of articles		reports cited in
			published in	published in		2017
			2015 and 2016	2015 and 2016
	A	7	15	4717	0.32%	29
	B	9	133	5029	2.64%	131
	C	16	472	8228	5.74%	359
	D	27	971	7704	12.60%	957
	E	18	334	3225	10.36%	181
	TOTAL	77	1925	28903	6.66%	1657

Table 2 :

 2 Projected impact factor (IF) whether or not case reports are published

	Bold values indicate significant differences
	SIGAPS	Mean true IF	Mean IF without case	p value (two-tail)	p value (one-tail)
	tier		reports
	A	4.639	4.644	0.155	0.077
	B	3.006	3.080	0.153	0.077
	C	2.367	2.457	0.029	0.015
	D	1.628	1.711	0.009	0.004
	E	0.758	0.769	0.109	0.054
	TOTAL	2.013	2.072	< 0.0001	< 0.0001

Conflict of interest: SB is a consultant with Zimmer outside this study. SD is a consultant with SERF, Euros and DePuy outside this study. PSM was compensated by Sanofi outside this study. GV is a consultant with FH Ortho outside this study. The other authors have no conflict of interest to disclose in which payment was received.

No funding was received for this study

Author contributions:

RE designed the study, collected data, did the statistical analysis, wrote the manuscript and made corrections JD contributed to the design of this study, data collection GV contributed to the design of this study, data collection, writing the article and corrections PSM contributed to correcting the article SD contributed to the design of this study and correcting the article SB contributed to the design of this study and correcting the article


Marieke H C Van Rijn

MSC Natalia Alencar De Pinho

PhD Jack F M Wetzels

Jan A J G Van Den Brand

Bénédicte Né

Dicte Stengel

Marieke Hc Van Rijn

MD Jan Ajg Van Den Brand

PhD Benedicte Stengel
email: benedicte.stengel@inserm.fr

Worldwide Disparity in the Relation Between CKD Prevalence and Kidney Failure Risk

Keywords: chronic kidney disease, kidney replacement therapy, disparity, international comparison, ecologic study

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Over the past two decades, knowledge about the epidemiology of chronic kidney disease (CKD) and its complications has advanced substantially worldwide. [START_REF] Jha | Chronic kidney disease: global dimension and perspectives[END_REF][START_REF] Nitsch | Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis[END_REF][START_REF] Thomas | Global Cardiovascular and Renal Outcomes of Reduced GFR[END_REF][START_REF] Caskey | A population approach to renal replacement therapy epidemiology: lessons from the EVEREST study[END_REF][START_REF] Liyanage | Worldwide access to treatment for end-stage kidney disease: a systematic review[END_REF][START_REF] Hill | Global Prevalence of Chronic Kidney Disease -A Systematic Review and Meta-Analysis[END_REF] The increasing availability of national registries of kidney replacement therapy (KRT) for kidney failure and the work by the Global Burden of Disease (GBD) consortium in recent years to search for and standardize CKD prevalence data from the many available population-based studies have made it possible to obtain a global picture of CKD burden from moderate to advanced stages. [START_REF]USRDS annual data report: Epidemiology of Kidney Disease in the United States[END_REF][START_REF] Mills | A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010[END_REF][START_REF] Bikbov | Disparities in Chronic Kidney Disease Prevalence among Males and Females in 195 Countries: Analysis of the Global Burden of Disease 2016 Study[END_REF] The most striking finding from these estimates is that the disparities across countries are much greater for KRT incidence than for CKD prevalence.

The Global Kidney Health Atlas, led by the International Society of Nephrology (ISN), recently provided a comprehensive overview of the capacity of health systems to deliver care for kidney failure worldwide. [START_REF] Bello | Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey[END_REF] This capacity remains a major determinant of the variations observed in KRT incidence in low-and middle-income countries. Large variations in KRT incidence may also exist, however, across countries where access to KRT is not restricted. Hallan et al first pointed out this discrepancy in 2006, showing that KRT incidence in the United States was 3 times higher than in Norway, despite similar CKD prevalence. They suggested that faster progression to kidney failure rather than a higher number of individuals at risk likely explains this difference. [START_REF] Hallan | International comparison of the relationship of chronic kidney disease prevalence and ESRD risk[END_REF] Since then, two studies have investigated potential explanatory factors for differences in CKD progression across countries. [START_REF] Bruck | Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe[END_REF][START_REF] Orlandi | A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts[END_REF] Nevertheless, no overview is available of the gaps in KRT incidence between countries with their links to CKD prevalence within and across world regions, although it would help in understanding the possible sources of variations.

We therefore studied the relations of CKD prevalence with the incidence of KRT for kidney failure and with all-cause and CKD-related mortality rates across countries, by region, both overall and by gender, and estimated the proportion of variance in these three latter health indicators that is explained by CKD prevalence.

Methods

Data sources

Chronic kidney disease prevalence

Crude (all ages) and age-standardized CKD prevalences in 2016, expressed as percentages, were extracted overall and by gender from the Global Health Data exchange, GBD Results Tool website (http://ghdx.healthdata.org/gbd-results-tool). In the GBD Study, CKD is defined by an estimated glomerular filtration rate < 60 ml/min/1.73m² or a need for KRT. Data that inform GBD estimates include microdata or tabulated data obtained from publications (systematic literature reviews), as well as other relevant data sources such as vital registrations, hospital data, and disease registries (citations available on http://ghdx.healthdata.org/gbd-2017/data-input-sources). Prevalence is estimated with a compartmental model that allows data to be incorporated for various epidemiological indicators, such as incidence and mortality rates, through an integrative Bayesian meta-regression.( 14) It is based on (one or multiple) individual (national representative or local) studies or other data sources within a country. When there is no data for that country available, modeling may consider information from other countries with similar epidemiological backgrounds.

Prevalence estimates were age-standardized by the GBD 2017 world standard population. [START_REF] Burden | Incidence Prevalence, Collaborators. Global, regional, and national incidence, [ prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study[END_REF] Incidence of kidney replacement therapy for kidney failure Kidney replacement therapy included dialysis or pre-emptive kidney transplantation and its incidence was expressed per million population (pmp). We used data gathered by the United States Renal Data System (USRDS) from national KRT registries worldwide willing to contribute data to the international comparison chapter of this report. We extracted data for the crude incidence of KRT

Global Burden of Disease regional classification system

The 61 countries or regions included in this study, because of the availability of KRT incidence, were classified into three regions or categories, using GBD super regions, defined by a combination of geographic location and country GDP, and based on cause of death patterns (http://www.healthdata.org/terms-defined), as follows: (14)

• High-income regions: high-income Asia Pacific (Japan, South Korea, and Singapore), Australasia (Australia and New Zealand), Western Europe (Andorra, Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, Malta, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, and the United Kingdom), Southern Latin America (Argentina, Chile, and Uruguay) and North America (Canada and the United States)

• Central and Eastern Europe: Lithuania, Slovakia, Latvia, Hungary, Russia, Bulgaria, Romania, Belarus, Serbia, Albania, Bosnia and Herzegovina, Macedonia, and Ukraine

• Other regions: Latin America (Jalisco [Mexico], Brazil, Peru, Colombia, and Guatemala), North Africa and Middle East (Qatar, Saudi Arabia, Kuwait, Iran, Turkey, and Jordan), South, East, and Southeast Asia (Hong Kong, Malaysia, Taiwan, Thailand, Philippines, Indonesia, and Bangladesh), and Southern Sub-Saharan Africa (South Africa).

Statistical Analysis

Estimates of CKD prevalence (%), KRT incidence (pmp), and all-cause and CKD-related mortality (per 100 000 population) were tabulated and are presented as median and ranges according to region, as described above (high-income, Central and Eastern Europe, or Other), overall and by gender. To study the relations with KRT incidence, we plotted crude KRT incidence rates against crude and ageadjusted CKD prevalence, by region, overall and by gender, and for the relations with mortality risk, age-adjusted all-cause or CKD-related mortality rates against age-standardized CKD prevalence, again by region, overall and by gender. In addition, we used linear regression models to estimate the proportion of variance (R-squared) in KRT incidence and mortality rates explained by CKD prevalence.

We tested the linearity assumption for all regression models, which was not satisfied for the analysis of the association with mortality rates and required log-transformation. Other model assumptions (normality of residuals, link function, and homoscedasticity) were checked with the Global Validation of Linear Models Assumptions "glvma" package. Analyses were performed in R version 3.4.2.

Results

Geographic variations in age-standardized CKD prevalence, by gender and region

The age-standardized prevalence of CKD stages 3-5 ranged from 5.5% to 10.4% (median 6.3%) in the high-income region, 7.6% to 13.7% (median 8.7%) in Central and Eastern Europe, and 7.4% to 13.1% (median 10.7%) in the Other region (Supplementary Table 1A). The prevalence of CKD was higher in women than in men in all countries except Sweden (Supplementary Table 1B).

Geographic variations in kidney replacement therapy incidence, by gender and region

Overall

Ecologic associations between age-adjusted CKD prevalence and KRT incidence

In the high-income region, there was a positive and statistically significant relation between the ageadjusted prevalence of CKD and KRT incidence (Figure 1). CKD prevalence explained 40% of the variation in KRT incidence, while 60% remained unexplained. Relations were similar when crude CKD prevalence was used (Supplementary Figure 1). In a subset of the 23 (of the 28 studied) high-income countries with available KRT incidence data stratified by gender, the percentage of explained variance was slightly lower in men than women (49% vs 56%, Supplementary Table 3). In Central and Eastern Europe, KRT incidence was negatively and statistically significantly related to both the crude) and age-adjusted prevalence of CKD and did not differ by gender. In contrast, in countries from the Other region, crude CKD prevalence was positively and significantly related to KRT incidence (explained variance = 37%; P = 0.007), but the relation was null with age-standardized prevalence.

Although differences in KRT incidence between countries with similar CKD prevalence were usually larger across than within regions, substantial intraregional variations were also observed. Western

Europe is the region with the smallest differences across countries, but KRT incidence was nonetheless 3 times higher in Greece than in Iceland despite their similar CKD prevalence. In South, East, and Southeast Asia, KRT incidence varied from 1 to 10, for small differences in CKD prevalence.

Ecologic associations between age-adjusted CKD prevalence and mortality risk

In the high-income region, CKD prevalence explained a very low percentage of the variation in mortality (2%), while it tended to explain a higher but still not significant percentage in Central and Eastern Europe and in the Other region (Figure 2). This percentage was similar for both genders in the high-income and Other regions, but differed strongly by gender, 47% in men vs 0% in women, in Central and Eastern Europe (Supplementary Table 3). Regarding CKD-related mortality, the association was positive and statistically significant (p=0.016) in high-income countries, negative (p = 0.042) in Central and Eastern Europe, and positive, but nonsignificant (p>0.10) in the Other region (Supplementary Figure 2)

Discussion

We confirm the well-known greater gaps in KRT incidence than in CKD prevalence between countries in all of the GBD regions. The main novelty of this study is to highlight the high percentage of variation in KRT incidence not explained by the prevalence of CKD even in high-income countries (60%) where access to dialysis is not restricted. For similar CKD prevalence, KRT incidence rate can be up to three times higher from one country to another, as between Iceland and Greece. These results also show an unexpected negative association between these two kidney health indicators in Central and Eastern Europe, together with a weak, but positive association of CKD prevalence with all-cause mortality. An overview of these ecologic associations we observed can help raise global awareness about the issues and challenges regarding kidney failure prevention and care .

Our results extend worldwide the observation of significant discrepancies in the KRT-to-CKD ratio between countries, as described previously between Norway and the US white population.( 11) Only a small fraction of individuals with CKD eventually progress to kidney failure, but if the variation in the number of individuals with CKD were the only explanation for that of KRT incidence, the ratio of KRT incidence to CKD prevalence would be similar across countries, and the percentage of variance explained would be 100%. In high-income countries, this percentage was 40%, which suggests that differences in the distribution of CKD risk factors play a substantial role in the variation of kidney failure incidence between countries. Nonetheless, although a meta-analysis of 19 general population-based studies from 13 European countries did find variations in CKD prevalence across these countries, differences in major CKD risk factors, including diabetes, hypertension, and obesity, did not appear to explain them well. [START_REF] Hill | Global Prevalence of Chronic Kidney Disease -A Systematic Review and Meta-Analysis[END_REF][START_REF] Mills | A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010[END_REF][START_REF] Bruck | CKD Prevalence Varies across the European General Population[END_REF][START_REF] Stel | International differences in chronic kidney disease prevalence: a key public health and epidemiologic research issue[END_REF][START_REF] De Nicola | Chronic kidney disease prevalence in the general population: heterogeneity and concerns[END_REF] The negative relation or lack of association observed in Central and Eastern Europe and in the Other region, in contrast, cannot be interpreted as the absence of an impact of CKD risk factors, most especially as CKD prevalence is higher in these regions than in high-income countries. [START_REF] Hill | Global Prevalence of Chronic Kidney Disease -A Systematic Review and Meta-Analysis[END_REF][START_REF] Mills | A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010[END_REF][START_REF] Bruck | CKD Prevalence Varies across the European General Population[END_REF][START_REF] Stel | International differences in chronic kidney disease prevalence: a key public health and epidemiologic research issue[END_REF][START_REF] De Nicola | Chronic kidney disease prevalence in the general population: heterogeneity and concerns[END_REF] In Central and Eastern Europe, the association of higher CKD prevalence with lower KRT incidence together with higher all-cause mortality may instead reflect 11) Two recent meta-analyses of CKD cohort studies have investigated this hypothesis with individual-level data. [START_REF] Bruck | Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe[END_REF][START_REF] Orlandi | A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts[END_REF] The European CKD Burden Consortium, which used a joint model to compare estimated glomerular filtration rate (eGFR) decline and mortality risk across nine cohorts from five European countries, showed that baseline patient profiles and CKD progression rates differed substantially between studies. [START_REF] Bruck | Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe[END_REF][START_REF] Orlandi | A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts[END_REF] These variations in CKD progression, however, persisted despite adjustment for baseline eGFR, age, sex, albuminuria, comorbidities, and use of renin-angiotensin system inhibitors. The international network of CKD cohorts (iNET-CKD) has also observed different baseline profiles and highly heterogeneous risks of CKD progression, KRT incidence, and mortality among individuals with CKD participating in eight cohort studies around the globe. [START_REF] Bruck | Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe[END_REF][START_REF] Orlandi | A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts[END_REF] This study also observed that adjustment for several patient characteristics and laboratory markers did not substantially attenuate the differences in outcomes. Its finding that the magnitude of the associations of individual-level predictors with clinical outcomes varied substantially across studies suggests that the setting and/or differences in populations may influence these differences. Another iNET-CKD study finding of considerable heterogeneity in blood pressure control and antihypertensive prescription patterns in CKD worldwide also indicates that clinical practices may have an effect. [START_REF] Pecoits-Filho | Prescription of reninangiotensin-aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care[END_REF][START_REF] De Pinho | Considerable international variation exists in blood pressure control and antihypertensive prescription patterns in chronic kidney disease[END_REF] Finally, because kidney failure incidence is assessed from dialysis and transplantation registries, factors linked to the management of transition to kidney failure and/or access to KRT may play a major role in the gaps observed between countries. (Table ) It is well-known that access to KRT is influenced by local policies, and that several countries such as the United States, Japan, South Korea, or Taiwan, have very liberal criteria for acceptance on dialysis, while many European countries, Australia and New Zealand have a less liberal acceptance policy, and most African, Asia, and central or Eastern European countries have very limited access. An ecologic study of 46 countries reported that gross domestic product (GDP) per capita and percentage of GDP spent on health care were independently associated with KRT incidence. [START_REF] Thomas | Global Cardiovascular and Renal Outcomes of Reduced GFR[END_REF][START_REF] Caskey | A population approach to renal replacement therapy epidemiology: lessons from the EVEREST study[END_REF][START_REF] Bello | Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey[END_REF][START_REF] Orlandi | A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts[END_REF][START_REF] Caskey | Global variation in renal replacement therapy for end-stage renal disease[END_REF] It also showed that in more developed countries, the private for-profit share of hemodialysis facilities was also associated with higher KRT incidence, This study and ours raise the issue of overtreatment related to early-start dialysis in countries with extremely high KRT incidence. In France, eGFR level at dialysis start explained a substantial part of the variations in KRT incidence between regions. [START_REF] Couchoud | The timing of dialysis initiation affects the incidence of renal replacement therapy[END_REF] Variations in the availability of conservative therapy may also have an impact in the elderly population, as suggested by the Global Kidney Health Atlas study. [START_REF] Bello | Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey[END_REF][START_REF] Davison | Executive summary of the KDIGO Controversies Conference on Supportive Care in Chronic Kidney Disease: developing a roadmap to improving quality care[END_REF] Overall, these meta-analyses highlight the complexity of the relations between CKD and KRT risk and the need for further investigation.

This study has several strengths including the large number of countries spread over the different GBD super regions with standardized estimates of kidney health indicators. Another strength is that we were able to assess the relations between CKD prevalence and KRT incidence by gender in many of these countries. We also looked at the relation between CKD prevalence and all-cause and CKDrelated mortality risk, a major competing risk for KRT in CKD.

The study also has a number of limitations. First, it is an ecologic study, and the associations observed at the country level may be different at the individual level. Further studies comparing the relationship of CKD to kidney failure risk at the individual level are needed to identify potentially modifiable risk factors and racial disparities. Second, the use of KRT registry data did not enable us to describe the association of CKD prevalence with kidney failure risk because KRT registries cannot capture patients who progress to kidney failure but do not have access to KRT, refuse dialysis, or receive conservative care. Moreover, age-standardized KRT incidence was not available. Third, CKD prevalence may have been affected by the use of different creatinine assays or GFR estimation equations across studies, [START_REF] Hill | Global Prevalence of Chronic Kidney Disease -A Systematic Review and Meta-Analysis[END_REF][START_REF] Mills | A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010[END_REF][START_REF] Bruck | CKD Prevalence Varies across the European General Population[END_REF][START_REF] Stel | International differences in chronic kidney disease prevalence: a key public health and epidemiologic research issue[END_REF][START_REF] De Nicola | Chronic kidney disease prevalence in the general population: heterogeneity and concerns[END_REF] although the GBD correction methods should have reduced these disparities by standardizing these estimates. Fourth, the available reference population for age-standardization was different for the WHO and the GBD statistics. However, while this may have had an impact on mortality rate and CKD prevalence estimates, it should not have affected the associations we observed. Finally, the aggregation of countries with very diverse CKD epidemiology in one single "Other" group may be controversial, but the small number of these countries precluded a more detailed stratification.

In conclusion, this ecologic study highlights the large proportion of the global variation in KRT incidence that is apparently not explained by the number of individuals with CKD. While differences in health care resources are an obvious explanation of disparities in access to KRT, at least partly, in low-and middle-income countries, other hypotheses should be assessed for high-income countries, such as variations in clinical practice patterns intended to slow CKD progression and/or manage the transition to KRT. [START_REF] Dienemann | International Network of Chronic Kidney Disease cohort studies (iNET-CKD): a global network of chronic kidney disease cohorts[END_REF][START_REF] Mariani | The CKD Outcomes and Practice Patterns Study (CKDopps): Rationale and Methods[END_REF] The issue of dialysis overtreatment is scarcely discussed and may receive greater attention from both the patients and public health perspective. International comparisons at both patient and provider levels are necessary to investigate the relative impact of individual characteristics, physician practices, and local policies on the incidence of KRT. Legend: CKD, chronic kidney disease.

Variations in life expectancy-

  and distribution of CKD risk factors Life expectancy • Competing risk of mortality Heterogeneity in the prevalence of CKD risk factors • Ethnicity, race • Genetic risk factors • Environmental risk factors socioeconomic factors and working conditions lifestyle, diet, and access to clean water obesity, diabetes, and hypertension nephrotoxic medications, herbal remedies, and environmental nephrotoxins infections • Poor maternal and fetal health (low birth weight, premature birth) Acute kidney injury as a risk factor for CKD Variation in risk factors for CKD progression (GFR decline) to kidney failure • Variation in risk factors for CKD progression -Albuminuria -Diabetes, hypertension -Lifestyle (smoking status, physical activity) • Acute-on-chronic kidney disease as a risk factor for CKD progression • Heterogeneity in clinical practices -Use of ACEI/ARB, blood pressure control -Dietary counseling (sodium, protein) Variations in access to kidney replacement therapy • Variations in health resources -Gross domestic product (GDP) Health expenditure as % GDP -Private vs public share of health expenditure -Fee for service -Out of pocket expenses • Practice pattern regarding initiation of kidney replacement therapy -GFR at dialysis initiation (early versus late dialysis start) -Conservative therapy for elderly CKD patients

Figure 1 :

 1 Figure 1: Incidence of KRT incidence according to age-standardized CKD prevalence, by region.

Figure 2 :

 2 Figure 2: Age-standardized all-cause mortality according to age-standardized CKD prevalence, by region.

Geographic variations in age-adjusted all-cause and CKD-related mortality rate, by gender The

	Africa in the Other region (median 640) (Supplementary Table 2A). All-cause mortality rates were
	higher in men than in women in all countries, with sex ratios ranging from 1.15 in Kuwait to 2.2 in
	Lithuania. The age-standardized CKD-related mortality rate ranged from 2.5 to 42.4 per 100 000 in
	the high-income region, from 3.5 to 17 in Central and Eastern Europe, and from 2.6 to 45.2 in the
	Other region.

, KRT incidence rates were highest in Taiwan (493 pmp), the USA (378 pmp), Mexico (355 pmp) and Thailand (345 pmp) and lowest in South Africa (22 pmp), Ukraine (32 pmp), Bangladesh, and Belarus (51 pmp). The median KRT incidence was 155 pmp, ranging from 89 to 378 in the high income region, 107 pmp ranging from 32 to 222 in Central and Eastern Europe, and 140 pmp, ranging from 22 to 493 in the Other region. The incidence was higher in men than women in all countries but one, with sex ratios ranging from 1.04 in Bulgaria to 2.5 in Estonia. In Jordan more women (70 pmp) than men (51 pmp) received treatment for KRT. age-standardized all-cause mortality rate per 100 000 ranged from 299 in Japan to 555 in Argentina in the high-income region (median 360), from 525 in Estonia and Bosnia Herzegovina to 798 in Russia in Central and Eastern Europe (median 647), and from 523 in Qatar to 1213 in South

  the combination, at the population level, of poor population health with a health care system with inadequate capacity. Several CKD risk factors are well established, including genetic, socioeconomic, and environmental risk factors, as well as poor maternal and fetal health. A landmark article reporting the conclusions of an ISN CKD summit on Global Kidney Health in 2016 updated these factors, which are summarized in the Table.[START_REF] Jha | Chronic kidney disease: global dimension and perspectives[END_REF][START_REF] Levin | Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy[END_REF] These risk factors might be attenuated by promoting healthy lifestyles, improved education of the public and of health practitioners, and strategies to improve maternal and fetal health.Although heterogeneity in the prevalence of CKD risk factors explains part of the variance in KRT incidence, this study shows that a significant part of this variance remains unexplained. Several hypotheses can be generated including variations across countries in risk factors for CKD progression or in access to KRT, as listed in the Table.Hallan et al first suggested that slower progression to

kidney failure rather than a smaller number of individuals could account for the lower incidence of KRT in Norway than in the US.(

Table Potential sources of international variations in the relation between CKD prevalence and the risk to progress to kidney failure requiring KRT Variation in methods to estimate CKD prevalence

 Potential • Sampling method and sample representativeness of country population • Creatinine assay and GFR estimating equation

Acknowledgments

Marieke HC van Rijn was supported by grants from the Radboud Institute for Health Sciences and the Dutch Kidney Foundation (150KK109). We thank Joe Coresh for his helpful comment in this study and Jo-Ann Cahn for her editorial assistance. ACEI: angiotensin-converting-enzyme inhibitors, ARB: angiotensin receptor blockers, CKD: Chronic kidney disease, GFR: glomerular filtration rate, KRT: kidney replacement therapy

Marieke HC van Rijn was supported by grants from the Radboud Institute for Health Sciences and the Dutch Kidney Foundation (150KK109).

Disclosure

Marieke HC van Rijn (None), Natalia Alencar de Pinho (None), Jack F Wetzels (None) , Jan AJG van den Brand (None), Benedicte Stengel (None) None


Pierre Martinot
email: pierre.martinot@hotmail.fr

Julien Dartus

Arthur Justo

Hicham Riouach

Paul Cremer

Charles-Henri Flouzat-Lachaniette

Philippe Hernigou

Luc Kerboull

Philippe Chiron

Does augmented core decompression decrease the rate of collapse and improve survival of femoral head avascular necrosis? Case-control study comparing 184 augmented core decompressions to 79 standard core decompressions with a minimum 2 years' follow-up

Keywords: osteonecrosis of the femoral head, avascular necrosis, core decompression, stem cells, bone grafting

la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Abstract

Introduction

Avascular necrosis of the femoral head often progresses to femoral head collapse if not treated. Conservative treatment yields highly variable results and is not standardized, mainly because it is typically evaluated in small patient populations. This led us to conduct a large retrospective comparative study with the goals of 1) analyzing survival and functional outcomes, 2) looking for differences in survival between core decompression techniques (standard versus augmented), and 3) studying the risk factors for femoral head collapse and revision by arthroplasty.

Hypothesis

Core decompression limits the number of patients who suffer femoral head collapse requiring arthroplasty at 2 years' follow-up.

Methods

This multicenter, comparative, retrospective study analyzed 330 patient records where at least 2 years' follow-up was available. Sixty-two patients were excluded from the analysis: 5 had a stage III with collapse, 5 were lost to follow-up, 2 died within 24 months of the procedure and 50 had incomplete data. The study included 263 patients with a mean age of 42 years (15.7-70). In the Ficat Classification, there were 51 cases of stage I necrosis, 186 cases of stage II and 22 cases of stage II with crescent sign (transition stage). The Kerboull angle on radiographs was between 5° and 20° in 40 patients, between 20° and 40° in 107 patients, between 40° and 60° in 52 patients and more than 60° in 29 patients. A standard core decompression was done in 79 patients and an augmented one in 184 patients. The more severe AVN cases (stage II) were more likely to be treated by augmented CD (160/184 patients, 87%) than by standard CD (48/79 patients, 61%) (p < 0.001).

Results

In the 263 patients, the overall survival (no arthroplasty at 2 years) was 73% (196/263). At 2 years, the survival rate (without arthroplasty) was 71% (56/79) in the standard CD group versus 76% (140/184) in the augmented CD group. This difference was significant when adjusted for Ficat stage and Kerboull angle (HR = 0.457, 95% CI [0.247-0.844] (p = 0.012)).

When the survival data was adjusted to the Ficat stage, augmented CD was better than standard CD with 10-year survival of 58.1% vs 57.9% (p = 0.0082). More than 30% necrosis volume increased the risk of failure (HR = 3.291 95%CI [1.494-7.248] (p = 0.0031)). Also, a

Introduction

Idiopathic avascular necrosis (AVN) of the femoral head progresses with pain towards femoral head collapse that then requires hip arthroplasty in patients who are often still working [START_REF] Mont | The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review[END_REF][START_REF] Fukushima | Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head[END_REF]. The risk of progression for non-collapsed stages during a purely medical treatment has led to the development of conservative surgical techniques [START_REF] Fukushima | Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head[END_REF][START_REF] Marciniak | Osteonecrosis of the femoral head. A study of 101 hips treated with vascularized fibular grafting[END_REF]. Better use of imaging modalities such as MRI, radiographs and CT scan provide earlier diagnosis and confirm the absence of subchondral fracture. While the risk factors for AVN have been extensively described [START_REF] Cui | Multicentric epidemiologic study on six thousand three hundred and ninety-five cases of femoral head osteonecrosis in china[END_REF][START_REF] Yoon | No differences in the efficacy among various core decompression modalities and non-operative treatment: a network metaanalysis[END_REF], the indications for conservative treatment have not been.

Simple core decompression (CD) proposed in 1964 by Ficat [START_REF] Ficat | Therapeutic results of drill biopsy in primary osteonecrosis of the femoral head (100 cases)[END_REF][START_REF] Ficat | Long-term results of the forage-biopsy in grade I and II osteonecrosis of the femoral head. Apropos of 133 cases re-examined after an average time of 9 years 6 months[END_REF] for cases without subchondral fracture are better than osteotomy because it does not deform the proximal femur, thus preserving the mechanical conditions needed to subsequently perform total hip arthroplasty (THA) if needed. Also, standard CD does not require the fibula to be removed, a bone that is typically used as a vascularized bone graft [START_REF] Marciniak | Osteonecrosis of the femoral head. A study of 101 hips treated with vascularized fibular grafting[END_REF][START_REF] Calori | Core decompression and biotechnologies in the treatment of avascular necrosis of the femoral head[END_REF][START_REF] Mont | Nontraumatic osteonecrosis of the femoral head: where do we stand today? a ten-year update[END_REF][START_REF] Hernigou | Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress[END_REF][START_REF] Hernigou | Osteonecrosis repair with bone marrow cell therapies: state of the clinical art[END_REF]. Recent studies propose using stem cells to improve the effectiveness of CD and increase the survival rate of AVN [START_REF] Hernigou | Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress[END_REF][START_REF] Hernigou | Osteonecrosis repair with bone marrow cell therapies: state of the clinical art[END_REF][START_REF] Xu | Autologous stem cells combined core decompression for treatment of avascular necrosis of the femoral head: a systematic meta-analysis[END_REF][START_REF] Zhou | New advances in stem cell therapy for osteonecrosis of the femoral head[END_REF]. They may reduce the number of patients who progress to head collapse when the diagnosis is made early enough. However, no large studies have been done in France comparing standard to augmented CD. This led us to conduct a large retrospective comparative study with the goals of 1) analyzing survival and functional outcomes, 2) looking for differences in survival between core decompression techniques (standard versus augmented), and 3) studying the risk factors for collapse and revision by arthroplasty. We hypothesized that core decompression limits the number of patients who suffer a collapse requiring arthroplasty at 2 years' follow-up [START_REF] Mont | The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review[END_REF].

Methods

Patients

In the context of the 2018 SOFCOT symposium on this topic, 330 patient records from 1975 to 2016 were analyzed. Sixty-two patients were excluded from the analysis: 5 had undergone CD for a stage III in the Arlet and Ficat classification [START_REF] Ficat | Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment[END_REF], 5 were lost to follow-up before 2 years, 2 died within 24 months of the procedure and 50 had incomplete data for estimating survival. Proximal femoral osteotomy and vascularized fibula grafts were not taken into account since so few cases were done (1 and 4 patients, respectively) (Figure 1).

Excluded were patients with femoral head collapse (stage III in Ficat classification, stage 4 in ARCO classification) [START_REF] Ficat | Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment[END_REF][START_REF] Gardeniers | Association Research Circulation Osseous): Committee on terminology and classification[END_REF], patients with history of bone radiation, post-traumatic osteonecrosis, inflammatory arthritis, or septic arthritis. Patients in whom we could not analyze the main endpoints (head collapse at 2 years and revision by THA) were excluded.

At a mean follow-up of 31.4 ± 55.2 months (24-505 months), 79 simple CD or 30% (79/263) and 184 augmented CD or 70% (184/263) were analyzed (Table 1). Among the augmented CD procedures, 84 were done with autologous cancellous bone fragments, 65 with bonemarrow derived stem cells, 5 with hematopoietic stem cells including platelet-rich plasma (PRP), 3 with bone marrow-derived stem cells and PRP, and 27 with non-concentrated bone marrow + rhBMP2 injection (Genetics Institute, Boston, MA, USA) [START_REF] Lieberman | Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein[END_REF] (Table 2).

Of the 263 patients included in the analysis, the mean age was 42 ± 13 years (16.5-70 years). The mean weight, height, and body mass index (BMI) were 80 ± 17 kg, 174 ± 8 cm, 26.2 ± 5.3 kg/m 2 , respectively. Thirty-three patients (13%) had a BMI above 30 (33/263).

There were more men (209) than women (54). The patients were Charnley A in 70 cases, Charnley B in 156 cases and Charnley C in 9 cases [START_REF] Charnley | Rate of wear in total hip replacement[END_REF] (28 cases not specified (10%)). The right side was affected in 141 patients and the left side in 122.

Among the risk factors studied, 129 patients were smokers, 92 had undergone corticosteroid therapy, 61 were alcoholics, 42 had a chronic disease (Crohn's disease, cancer, etc.), 39 had high blood pressure, 31 had high blood lipids, 19 were asthmatic, 13 had arteritis, 13 were diabetic, 9 had systemic lupus, 8 had a received a kidney transplant, 3 had sickle cell disease, 3 were taking anticoagulants and 1 was undergoing dialysis. The two groups were not comparable in terms of medical history, with more asthmatic patients in the augmented CD group and more patients who had a kidney transplant and who were alcoholics in the standard CD group (Table 1).

In the Ficat classification of AVN of the femoral head [START_REF] Ficat | Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment[END_REF], 51 patients were stage 1, 186 were stage 2, 22 were transition stage (stage 2 with crescent sign) (4 not specified (1.5%)). The Kerboull angle [START_REF] Kerboull | The conservative surgical treatment of idiopathic aseptic necrosis of the femoral head[END_REF] on radiographs was between 5° and 20° in 40 patients, between 20° and 40° in 107 patients, between 40° and 60° in 52 patients and more than 60° in 29 patients (35 not specified (13%)). The necrosis volume on MRI was less than 15% in 45 patients, 15% to 30% in 121 patients and more than 30% in 60 patients (37 not specified (14%)).

The mean preoperative clinical outcome scores were 5.5 [START_REF] Mont | The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review[END_REF][START_REF] Fukushima | Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head[END_REF][START_REF] Marciniak | Osteonecrosis of the femoral head. A study of 101 hips treated with vascularized fibular grafting[END_REF][START_REF] Cui | Multicentric epidemiologic study on six thousand three hundred and ninety-five cases of femoral head osteonecrosis in china[END_REF][START_REF] Yoon | No differences in the efficacy among various core decompression modalities and non-operative treatment: a network metaanalysis[END_REF][START_REF] Ficat | Therapeutic results of drill biopsy in primary osteonecrosis of the femoral head (100 cases)[END_REF][START_REF] Ficat | Long-term results of the forage-biopsy in grade I and II osteonecrosis of the femoral head. Apropos of 133 cases re-examined after an average time of 9 years 6 months[END_REF][START_REF] Calori | Core decompression and biotechnologies in the treatment of avascular necrosis of the femoral head[END_REF][START_REF] Mont | Nontraumatic osteonecrosis of the femoral head: where do we stand today? a ten-year update[END_REF][START_REF] Hernigou | Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress[END_REF] for the UCLA activity score [START_REF] Zahiri | Assessing activity in joint replacement patients[END_REF], 12.8 [START_REF] Ficat | Long-term results of the forage-biopsy in grade I and II osteonecrosis of the femoral head. Apropos of 133 cases re-examined after an average time of 9 years 6 months[END_REF][START_REF] Calori | Core decompression and biotechnologies in the treatment of avascular necrosis of the femoral head[END_REF][START_REF] Mont | Nontraumatic osteonecrosis of the femoral head: where do we stand today? a ten-year update[END_REF][START_REF] Hernigou | Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress[END_REF][START_REF] Hernigou | Osteonecrosis repair with bone marrow cell therapies: state of the clinical art[END_REF][START_REF] Xu | Autologous stem cells combined core decompression for treatment of avascular necrosis of the femoral head: a systematic meta-analysis[END_REF][START_REF] Zhou | New advances in stem cell therapy for osteonecrosis of the femoral head[END_REF][START_REF] Ficat | Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment[END_REF][START_REF] Gardeniers | Association Research Circulation Osseous): Committee on terminology and classification[END_REF][START_REF] Lieberman | Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein[END_REF][START_REF] Charnley | Rate of wear in total hip replacement[END_REF][START_REF] Kerboull | The conservative surgical treatment of idiopathic aseptic necrosis of the femoral head[END_REF] for the Merle d'Aubigné Postel (MDP) [START_REF] Merle D'aubigné | Numerical classification of the function of the hip[END_REF], 63.6 (11-100) for the Harris Hip score [START_REF] Harris | Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty[END_REF], and 3.2 (1-5) for the Devane activity score [START_REF] Devane | Three-dimensional polyethylene wear of a press-fit titanium prosthesis. Factors influencing generation of polyethylene debris[END_REF]. In terms of occupation before the surgery, 8 patients were unemployed, 69 were on medical leave, 33 worked seated, 62 alternated between sitting and standing, 36 worked while standing, 37 carried heavy loads and 10 were retired (Table 1).

The augmented CD group had significantly younger patients in it (41.2 ± 14 years versus 45.2 ± 11 years (p = 0.015)), had more severe disease (Stage 2 = 43/79 (54%) versus 143/263 (78%), Stage 2 with crescent sign = 5/79 (6%) versus 17/263 (9%) (p < 0.001)), had a larger Kerboull angle [START_REF] Kerboull | The conservative surgical treatment of idiopathic aseptic necrosis of the femoral head[END_REF] ((40° to 60° = 11/79 (14%) versus 41/263 (22%); more than 60° = 1/79 (1%) versus 28/263 (15%) (p = 0.002)). Thus, the patients in the augmented CD group had more advanced disease than those in the standard CD group.

Methods

The study included all patients with primary AVN of the hip who underwent conservative nonarthroplasty surgical treatment and who agreed to their data being used in the context of this study. Conservative surgery was divided into two groups: standard CD and augmented CD.

The CD technique was left up to the surgeon given the multicenter nature of this study.

Generally, multiple holes were made manually using a small-caliber trephine. This was the only intervention done in the standard CD group. In the augmented CD group, an adjunctive treatment was added (autograft, bone marrow or hematopoietic stem cells, with or without PRP) (Table 2).

Assessment methods

Current demographic, surgical and radiological data were collected either during an office visit, over the telephone or by consulting the medical records. Data on the treatment done, complications and other adverse events were collected throughout the hospital stay and during the follow-up period. The clinical outcomes consisted of the Devane score [START_REF] Devane | Three-dimensional polyethylene wear of a press-fit titanium prosthesis. Factors influencing generation of polyethylene debris[END_REF], the UCLA score [START_REF] Zahiri | Assessing activity in joint replacement patients[END_REF], the Harris Hip score [START_REF] Harris | Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty[END_REF], the MDP score [START_REF] Merle D'aubigné | Numerical classification of the function of the hip[END_REF] and the occupation before surgery. The change in these parameters was calculated from preoperative to follow-up. The radiographic analysis consisted of measuring the Kerboull angle [START_REF] Kerboull | The conservative surgical treatment of idiopathic aseptic necrosis of the femoral head[END_REF] on radiographs and the necrosis volume on MRI.

The main endpoint was the absence of THA for head collapse within 2 years of CD for AVN.

The secondary endpoints were the clinical scores, radiographic data, and complication rates.

The patient records were reviewed retrospectively irrespective of the surgery date as long as the follow-up was at least 24 months.

Data processing and statistical analysis

The quantitative variables were summarized by their mean and standard deviation or median and interquartile interval. The normality of the data distribution was verified graphically and using the Shapiro-Wilk test. Qualitative variables were described by their counts and percentage. If the sample size was large enough, qualitative variables were compared between groups using the Chi-square test. If this test could not be used (expected count < 8), the Fisher exact test was used. When the sample size was large enough, quantitative variables were compared between groups using Student's t test. If the data were not normally distributed, the Wilcoxon test was used instead.

The occurrence of head collapse and revision by THA was estimated using the Kaplan-Meier method. To look for risk factors for THA at 2 years postoperative, a proportional Cox risk model was used. The significance threshold was set at 0.05. The statistical analysis was performed with SAS software (version 9.4, SAS Institute, Cary NC, USA).

Results

Seven patients died more than 2 years after the CD procedure, an average of 80 months later (35-119 months). At 2 years' follow-up, 74% of all patients (196/263) had not undergone THA (Figure 2). When broken down by procedure, 71% (56/79) of patients who had undergone standard CD and 76% (140/184) of those who had undergone augmented CD did not require THA (Figs. 3 and4). Calculating the change (delta) between the preoperative measure and the final follow-up identified significantly better functional improvement after augmented CD than standard CD with 0.51 ± 2.1 versus -0.21 ± 1.95 for the UCLA score (p = 0.009), 11.56 ± 21.42 versus 18.69 ± 20.89 for the Harris Hip score (p = 0.019) and 1.18 ± 3.69 versus 2.49 ± 3.14 for the MDP (p = 0.020) (Table 3).

In terms of postoperative complications, there were two superficial infections, one pulmonary embolism and one pertrochanteric fracture. There were too few complications to look for a difference between groups (Table 4).

When the success of the procedure was analyzed relative to Ficat stage, the success rate was 84% for stage I (41/49), 66% for stage II (121/184) and 73% (16/22) for stage transition (stage II with crescent sign) (Table 5). When the success of the procedure was analyzed relative to the necrosis volume, the success rate was 74% for less than 15% volume (35/47), 84% for 15% to 30% volume (96/114) and 48% for volume greater than 30% (26/56) (Table 5). The subset of patients with more than 30% necrosis volume had a significantly higher risk of failure than the other patients [HR = 3.291, 95%CI [1.494-7.248] (p = 0.0031)] (Table 6).

When the success rate of the procedure was analyzed relative to the necrosis size (Kerboull angle on radiographs), the success rate was 76% for angles below 20° (29/38), 82% for angles between 20° and 40° (85/104), 55% for angles between 40° and 60° (27/100), 41% for angle greater than 60° (12/29) (Table 5). The subset of patients with necrosis size greater than 60° had a significantly higher risk of failure than the other patients [HR = 3.148, 95%CI [1.346-7.5] (p = 0.0083)] (Table 6). Thus the risk factors for failure of conservative treatment 6).

Discussion

In France, no large recent studies on the outcome of hips after conservative treatment for AVN have been conducted as far as we know. Our study found a high survival rate (74%) 2 years after CD. The overall survival rate of all techniques pooled, all necrosis volumes in stage I and II of the Ficat classification with THA due to head collapse as the endpoint was 74%, which appears to be clearly better than isolated medical treatment reported in the literature [START_REF] Ficat | Therapeutic results of drill biopsy in primary osteonecrosis of the femoral head (100 cases)[END_REF][START_REF] Lieberman | Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein[END_REF][START_REF] Mont | Core decompression and nonvascularized bone grafting for the treatment of early stage osteonecrosis of the femoral head[END_REF][START_REF] Andriolo | Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis[END_REF].

By factoring in the preoperative differences between groups (Kerboull angle and Ficat stage), the patients who underwent augmented CD had significantly better survival at 2 years (p = 0.012) and at the maximum follow-up (p = 0.0082). Given the introduction of cell therapy, several authors endorse doing CD in combination with stem cells to improve the hip survival (augmented CD) [START_REF] Andriolo | Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis[END_REF][START_REF] Papakostidis | The role of "cell therapy" in osteonecrosis of the femoral head. a systematic review of the literature and meta-analysis of 7 studies[END_REF][START_REF] Gangji | Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. surgical technique[END_REF][START_REF] Li | Comparison of bone marrow mesenchymal stem cells and core decompression in treatment of osteonecrosis of the femoral head: a meta-analysis[END_REF][START_REF] Piuzzi | Analysis of cell therapies used in clinical trials for the treatment of osteonecrosis of the femoral head: a systematic review of the literature[END_REF][START_REF] Wang | Core decompression combined with autologous bone marrow stem cells versus core decompression alone for patients with osteonecrosis of the femoral head: A meta-analysis[END_REF][START_REF] Hua | The efficacy and safety of core decompression for the treatment of femoral head necrosis: a systematic review and meta-analysis[END_REF]. Our statistical analysis took into account the dissimilarities in the two CD groups since there was a large share of severe necrosis cases in the augmented CD group (Ficat stage and Kerboull angle). We could not compare the augmented CD techniques among each other given the large differences between them (5 different techniques). Different techniques were used because the choice was left up to the surgeons who participated in our study. The magnitude of improvement in the functional scores that we assessed (UCLA, Harris, MDP) was better in the augmented CD group than in the standard CD group.

A large volume of necrosis on MRI and high Kerboull angle were risk factors for revision by THA, which is consistent with other published studies on this topic [START_REF] Rajagopal | Efficacy of core decompression as treatment for osteonecrosis of the hip: a systematic review[END_REF][START_REF] Mazières | Influence of the volume of osteonecrosis on the outcome of core decompression of the femoral head[END_REF]. Thus, it is crucial to carefully analyze these two parameters before considering doing CD [START_REF] Steinberg | Determining lesion size in osteonecrosis of the femoral head[END_REF]. While there was a statistical trend in stage II with crescent sign cases, we did not find an impact of the Ficat stage on the occurrence of head collapse, despite what is said in the literature [START_REF] Castro | Core decompression and conservative treatment for avascular necrosis of the femoral head: a meta-analysis[END_REF]. This may explain the uneven distribution of patients (Table 1 difference based on Ficat stage (p < 0.001)) in each group and the heterogeneous nature of the groups studied. The fact that patients with less than 15% necrosis volume (A in ARCO) had the same probability of needing THA than those with 15% to 30% necrosis volume (B in ARCO) is inconsistent and does not correspond to published data [START_REF] Mazières | Influence of the volume of osteonecrosis on the outcome of core decompression of the femoral head[END_REF]. This may be explained by the position of the necrosis [START_REF] Sugano | The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head[END_REF][START_REF] Escudier | Superimposition of maximal stress and necrosis areas at the top of the femoral head in hip aseptic osteonecrosis[END_REF], which was not evaluated in our study. Moreover, drilling 8 mm holes could weaken the subchondral bone; small size necrosis or volume < 10% was not always an indication for CD, since the natural history is more favorable [START_REF] Mont | The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review[END_REF]. Conversely, drilling 4 mm holes and injecting stem cells may not have these effects, although this needs to be confirmed.

Determining the clinical outcome scores in the entire study cohort was important because the patients with the worst preoperative scores (Devane, UCLA, Harris and MDP) were more likely to need THA. The direct relationship between the necrosis stage and the clinical symptoms explains this finding well in our opinion [START_REF] Hernigou | Fate of very small asymptomatic stage-I osteonecrotic lesions of the hip[END_REF]. Thus, it seems preferable to do conservative treatment in these patients since it primarily consists of patients with low grade necrosis on the Ficat classification, with smaller necrosis volume and size [START_REF] Lieberman | Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein[END_REF][START_REF] Tripathy | Management of femoral head osteonecrosis: current concepts[END_REF].

Our study has several limitations. 1) This was a retrospective study, which implies missing data (1% to 14% of main parameters) and exclusion of patients who did not have 2 years of follow-up available.

2) The population in our study was diverse and the study was not randomized. However, the large number of patients analyzed limits the impact of this factor.

3) We used recourse to THA for head collapse as the primary endpoint. This is certainly a bias because certain patients could have benefited from THA before they experienced head collapse or certain patients may have undergone CD later after pain symptoms appeared.

4) The augmented CD technique differed between participating sites. Thus, it is undeniable that the various CD done did not have the same impact on the clinical outcomes, which may contribute to bias. The fact that we could not do a sub-group analysis because these subgroups were too small limits our interpretation of how using these augmented CD techniques impacted the outcome. The difference in effectiveness between multiple CD versus standard CD has not been studied, although the first appears more effective [START_REF] Al Omran | Multiple drilling compared with standard core decompression for avascular necrosis of the femoral head in sickle cell disease patients[END_REF][START_REF] Mohanty | Management of non-traumatic avascular necrosis of the femoral head-a comparative analysis of the outcome of multiple small diameter drilling and core decompression with fibular grafting[END_REF]. 5) We did not look at the effect of the necrosis location on the risk of head collapse, although this appears to be linked to the collapse risk [START_REF] Escudier | Superimposition of maximal stress and necrosis areas at the top of the femoral head in hip aseptic osteonecrosis[END_REF]. It would be interesting to do a larger study to compare the effectiveness of various types of augmented CD techniques to each other.

Conclusion

Doing CD for femoral head AVN reduces the need for THA in a large portion of patients at 2 years (74%). A large necrosis volume (> 30%) and large necrosis size (>60°) were risk factors for revision by THA. Augmented CD improves 2-year survival and long-term survival after adjusting for preoperative characteristics (Kerboull angle and Ficat stage). Augmented CD yields better clinical outcomes. While the literature suggests adding stem cells in these patients' hip, the large range of techniques employed in this study precludes us from drawing any conclusions about this method.

Outside this study, Philippe Hernigou declares being a consultant for Ceraver, Philippe Chiron declares having received royalties from Adler, Luc Kerboull declares being a consultant for Medacta and Zimmer-Biomet, Charles Henri Flouzat Lachaniette declares being a consultant for Ceraver and Lépine. The other authors have no conflict of interest outside this study.

Funding: this study was funded by the SOFCOT

  The survival at 2 years and the maximum follow-up was not statistically different based on the standard statistical analysis (at 2 years, HR = 0.816 95%CI [0.493-1.35] (p = 0.429) / and at maximum follow-up, HR = 0.936 95%CI [0.619-1.41] (p = 0.756)) (Figs. 3 and 4). After adjusting the data to account for initial differences in Kerboull angle and Ficat stage, the augmented CD procedure had significantly better survival than standard CD at 2 years: 70.9% versus 76.1% [HR = 0.457 95%CI [0.247-0.844] (p = 0.012)] and at the maximum follow-up 57.9% versus 58.1% [HR = 0.504, 95%CI [0.304-0.83] (p = 0.0082)].At the review, the mean clinical scores were 5.7 (1-10) for the UCLA, 15[START_REF] Ficat | Long-term results of the forage-biopsy in grade I and II osteonecrosis of the femoral head. Apropos of 133 cases re-examined after an average time of 9 years 6 months[END_REF][START_REF] Calori | Core decompression and biotechnologies in the treatment of avascular necrosis of the femoral head[END_REF][START_REF] Mont | Nontraumatic osteonecrosis of the femoral head: where do we stand today? a ten-year update[END_REF][START_REF] Hernigou | Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress[END_REF][START_REF] Hernigou | Osteonecrosis repair with bone marrow cell therapies: state of the clinical art[END_REF][START_REF] Xu | Autologous stem cells combined core decompression for treatment of avascular necrosis of the femoral head: a systematic meta-analysis[END_REF][START_REF] Zhou | New advances in stem cell therapy for osteonecrosis of the femoral head[END_REF][START_REF] Ficat | Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment[END_REF][START_REF] Gardeniers | Association Research Circulation Osseous): Committee on terminology and classification[END_REF][START_REF] Lieberman | Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein[END_REF][START_REF] Charnley | Rate of wear in total hip replacement[END_REF][START_REF] Kerboull | The conservative surgical treatment of idiopathic aseptic necrosis of the femoral head[END_REF] for the MDP, 81.6 (30-100) for the Harris, and 3.2 (1-5) for the Devane. In terms of occupation at the final assessment, 14 patients were unemployed, 65 were on medical leave, 23 did seated work, 70 alternated between sitting and standing, 40 worked while standing, 24 carried heavy loads and 18 were retired.

  were necrosis volume above 30% [HR = 3.291 95%CI [1.494-7.248] (p = 0.0031)] and necrosis angle greater than 60° [HR = 3.148 95%CI [1.346-7.5] (p = 0.0083)]. The functional outcome scores were also predictive of progression to head collapse at 2 years (stage III). Indeed, patients who had low preoperative clinical scores (Devane, UCLA, Harris Hip and MDP) had a significantly higher risk of progression to head collapse with respectively, HR = 0.797 (95%CI [0.637-0.997] (p = 0.0468)), HR = 0.873 95%CI ([0.775-0.983] (p = 0.0253)), HR = 0.973 (95%CI [0.959-0.988] (p = 0.003)) and HR = 0.895 (95%CI [0.809-0.997] (p = 0.0453)) (Table

Figure 1 :Figure 2 :Figure 3 :Figure 4 :

 1234 Figure 1: Study flow chart for inclusions

Figure 1 :

 1 Figure 1: Study flow chart for inclusions

Table 1 : Preoperative characteristics of the patients

 1

	Technique

Table 2 : Type of augmented core decompression (CD)

 2

	Number (% augmented CD)

Table 3 : Change in clinical outcome scores from preoperative to final follow-up

 3

		Technique	Standard CD	Augmented CD	p value
	Change in Devane score [22]	Mean	-0.19 ± 0.95	0.009 ± 1.15
	Follow-up -preop	Median (Q1;Q3)	0(-1; 0)	0(0; 1)	0.11
		Min-Max	-3; 2	-3; 3
	Change in UCLA score [19]	Mean	-0.21 ± 1.95	0.51 ± 2.10
	Follow-up -preop	Median (Q1;Q3) 0(-1; 0)	0(-1; 2)	0.009
		Min-Max	-6; 5	-7; 6
	Change in Harris Hip score [21] Mean	11.56 ± 21.42	18.69 ± 20.89
	Follow-up -preop	Median (Q1;Q3)	10(-7; 28)	23(0; 32)	0.019
		Min-Max	-22; 53	-31; 66
	Change in MDP score [20]	Mean	1.18 ± 3.69	2.49 ± 3.14
	Follow-up -preop	Median (Q1;Q3)	2(-2; 4)	3(0; 5)	0.020
		Min-Max	-5; 10	-6; 10
	Bold values indicate significant differences
	MDP: Merle d'Aubigné Postel score

Table 4 : Postoperative complications

 4

	Complications	Standard CD	Augmented CD	p value
		(% total pop.)	(% total pop.)
	None	78 (98.7)	181 (98.4)
	Pulmonary embolism	0	1 (0.35)	ND
	Fracture	0	1 (0.35)	ND
	Superficial infection	1 (1.3)	1 (0.35)	ND
	ND: Not determined since count is less than 8

Table 5 : Survival free of THA at 2 years

 5

			Standard CD	Augmented CD
		Methods			p value
			n/N (%)	n/N (%)
	Classification	Stage 1	27/31 (87.1)	16/20 (80.0)	0.70
	Arlet & Ficat [14]
		Stage 2	26/43 (60.5)	107/143 (74.8)	0.067
		Stage 2 with	3/5 (60.0)	15/17 (88.2)	ND
		crescent sign
	MRI volume	Less than 15°	9/12 (75.0)	28/33 (84.8)	0.66
		15-30%	25/31 (80.6)	79/90 (87.8)	0.37
		More than 30%	13/22 (59.1)	20/38 (52.6)	0.63
	Kerboull angle [18] 5° to 20°	10/14 (71.4)	22/26 (84.6)	0.42
		20° to 40°	21/28 (75.0)	71/79 (89.9)	0.063
		40° to 60°	5/11 (45.5)	27/41 (65.9)	0.30
		More than 60°	0/1 (0.0)	14/28 (50.0)	ND

ND: Not determined since count is less than 8; Bold values indicate significant differences

Table 6 : Risk factors for revision by THA at 2 years postoperative

 6 Bold values indicate significant differences MDP: Merle d'Aubigné Postel score * a low clinical score is associated with a higher probability of revision by THA at 2 years

	Risk factor	Hazard ratio	95% CI	p value
	Arlet & Ficat stage [14]
	Stage 2	1.277	0.455-3.589	0.642
	Stage 2 with crescent sign	0.526	0.096-2.873	0.459
	Kerboull angle [18]
	20-40°	0.619	0.186-2.058	0.434
	40-60°	2.431	0.8-7.388	0.117
	> 60°	3.178	1.346-7.5	0.0083
	Volume on MRI
	15-30%	0.879	0.305-2.53	0.811
	> 30%	4.163	1.494-7.248	0.0031
	UCLA score [19]	0.873*	0.775-0.983	0.0253
	Devane score [22]	0.797*	0.637-0.997	0.0468
	Harris score [21]	0.973*	0.959-0.988	0.0003
	MDP score [20]	0.895*	0.803-0.997	0.043

Acknowledgements

The SOFCOT members who included patients: Pierre Martinot (Lille), Philippe Chiron (Toulouse), Arthur Justo (Toulouse), Zainoul Jaffarbandjee (Réunion), Hicham Riouach (Clermont Ferrand), Jean Marc Puch ((Nice), Thierry Fabre (Bordeaux), Charles Dacheux (Bobigny), Erwan Pansard (Boulogne), Henri Migaud (Lille), Antoine Desseaux (Brest), Charles De Lambilly (Royan), Richard Ballas (Réunion), Antoine Gabrion (Amiens), Katsumi Kaneko (Nagano, Japan)

Conflict of interest:

None of the authors have conflicts to declare related to this study.

Author contributions:

P. Martinot: acquisition, analysis and interpretation of data, writing of article J. Dartus: analysis of data and critical review of the article for intellectual content A. Justo: acquisition of data H. Riouach: acquisition, analysis and interpretation of data P. Cremer: acquisition, analysis and interpretation of data CH. Flouzat Lachaniette: acquisition, analysis and interpretation of data; surgical procedures P. Hernigou: surgical procedures; critical review of article for intellectual content L. Kerboull: acquisition, analysis and interpretation of data; surgical procedures P. Chiron: acquisition, analysis and interpretation of data; surgical procedures; critical review of article for intellectual content; final approval of version being submitted.