Fig. 2. Intraoral radiograph of an immediately placed post-extractive dental implant with a full contour zirconia restoration after 1 year (same patient as in Fig. 1)
Fig. 2. Intraoral radiograph of an immediately placed post-extractive dental implant with a full contour zirconia restoration after 1 year (same patient as in Fig. 1)
Fig. 1. Pre-operative panoramic radiograph of a failing molar in position 36
Fig. 1. Pre-operative panoramic radiograph of a failing molar in position 36
Â
Agreement percentage (n = 11)
Presence of shame
0.0
Self-confidence has decreased
0.0
Evades eating with the implant
9.1
The ability to chew has decreased
0.0
Implant influences speech
0.0
Implant influences taste
0.0
Not satisfied with the colour of the crown
0.0
Not satisfied with the form of the crown
0.0
Not satisfied with ...
Bone change (mm)n = 11mean (SD)− 0.17 mm (0.73)> − 2.0 to − 1.51 (9.1)> − 1.5 to − 1.00 (0.0)> − 1.0 to − 0.52 (18.2)> − 0.5 to 0.04 (36.4)> 0.0 to 0.52 (18.2)> 0.5 to 1.02 (18.2)Table 4 Mean value, standard deviation, and frequency distribution (percentages) of marginal bone change between 1 month after restoration placement (T1) and 1 year in ...
Bone level (mm)n = 15Mean (SD)− 0.94 mm (0.54)> − 2.5 to − 2.01 (6.7)> − 2.0 to − 1.52 (13.3)> − 1.5 to − 1.04 (26.7)> − 1.0 to − 0.55 (33.3)> − 0.5 to 0.03 (20.0)Table 3 Mean value, standard deviation, and frequency distribution (percentages) of marginal bone level at 1 month after restoration placement (T1)
 T1 (n = 15)T12 (n = 11)Plaque indexScore 0, 15 (100%)Score 0, 11 (100%)Calculus indexScore 0, 15 (100%)Score 0, 11 (100%)Gingival indexScore 0, 15 (100%)Score 0, 11 (100%)Bleeding indexScore 0, 15 (100%)Score 0, 10 (91%)Score 1, 1 (9%)Probing depth in mm (sd)2.0 (0.9)1.9 (0.8)Table 2 Frequencies and percentages of plaque index scores (possible score 0–3), calculus index scores (possibl...
Mean age in years (sd, minimum-maximum)
57 (6.6, 44–67)
Gender (number male/female)
6/9
Reason of failure (severe caries/crown fracture/root fracture)
3/6/6
Implant position (maxilla/mandible)
7/8
Implant position (in between teeth/no tooth distally)
11/4
Â
Table 1 Baseline characteristics of the study group
Meijer, H.J.A., Raghoebar, G.M. Immediate implant placement in molar extraction sites: a 1-year prospective case series pilot study. Int J Implant Dent 6, 3 (2020). https://doi.org/10.1186/s40729-019-0201-7
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Received: 29 October 2019
Accepted: 11 December 2019
Published: 12 February 2020
DOI: https://doi.org/10.1186/s40729-019-0201-7
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were m...
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This clinical study was conducted in accordance with the World Medical Association Declaration of Helsinki (version VI, 2002). The Medical Ethical Committee of the University Medical Center Groningen considered this case series study not subject to the Medical Research Involving Human Subjects Act (Number M15.184100). The study was registered at the Netherlands Trial Register (Number NL8117). Afte...
Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, PO Box 30.001, NL-9700 RB, Groningen, The Netherlands
Henny J. A. Meijer & Gerry M. Raghoebar
Department of Implant Dentistry, University Medical Center Groningen, Groningen, The Netherlands
Henny J. A. Meijer
You can also search for this author in PubMed Google Scholar
You can also search for this author in...
An unrestricted grant from Nobel Biocare Services AG funded the 1-year clinical study; implant materials were provided (study code: 2015-1365).
Tallarico M, Xhanari E, Pisano M, Gatti F, Meloni SM. Molar replacement with 7 mm-wide diameter implants: to place the implant immediately or to wait 4 months after socket preservation? 1 year after loading results from a randomised controlled trial. Eur J Oral Implantol. 2017;10:169–78.
Checchi V, Felice P, Zucchelli G, Barausse C, Piattelli M, Pistilli R, Grandi G, Esposito M. Wide diameter i...
Hamouda NI, Mourad SI, El-Kenawy MH, Maria OM. Immediate implant placement into fresh extraction socket in the mandibular molar sites: a preliminary study of a modified insertion technique. Clin Implant Dent Relat Res. 2015;17(Suppl 1):e107–16. https://doi.org/10.1111/cid.12135.
Demircan S, Çankaya AB. Is immediate implant placement possible in the maxillary molar area? An anatomical study. Qu...
Gallucci GO, Hamilton A, Zhou W, Buser D, Chen S. Implant placement and loading protocols in partially edentulous patients: a systematic review. Clin Oral Implants Res. 2018;29(Suppl 16):106–34. https://doi.org/10.1111/clr.13276.
Slagter KW, Den Hartog L, Bakker NA, Vissink A, Meijer HJA, Raghoebar GM. Immediate placement of dental implants in the esthetic zone: a systematic review and pooled a...
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Within the limitations of this study, it has been demonstrated that immediate placement of regular diameter implants in molar post-extraction sites of maxilla and mandible resulted in a high implant failure rate during a 1-year follow-up period.
In an attempt to incorporate the concept of patient engagement, this study investigated the patients’ satisfaction with the rehabilitated posterior region by assessing specific patient-centred outcomes. This was done by the patients filling out the established questionnaire 1 year after restoration placement [26, 27]. All the questioned outcome measures showed high patient satisfaction which is...
The mean marginal bone level was 0.94 mm below the neck of the implant at 1 month after restoration placement (T1). The optimal position of the peri-implant bone after a maturation period should be at the same level as the neck of the implant. This means that part of the biological width of the present study, which is acting as a barrier, was in contact with the implant surface roughness and w...
Immediate placement of regular diameter implants in molar post-extraction sites of the maxilla and mandible resulted in a high implant failure rate during a 1-year follow-up period.
The implant survival rate was 73.3% after 1Â year in function. The performance of immediate placements in post-extraction sites was also analysed in the Cafiero et al., Atieh et al., Tallarico et al., and Checchi et a...
All 15 consecutive patients eligible to join the study on the basis of the inclusion and exclusion criteria agreed to participate in this study. The patient characteristics are depicted in Table 1. All implant-supported restorations had natural antagonistic teeth. Four of the 15 patients treated had a mobile implant, which had to be removed (in two patients 3 months after crown placement and in...
Radiographs were taken and evaluated 1 month and 12 months after restoration placement using a parallel technique, with an X-ray holder for periapical radiographs. They were analysed using a specially designed computer software to perform linear measurements on digital radiographs. The calibration was carried out in the vertical plane of each radiograph by using the known distance of the implan...
An impression was made at implant level 2Â weeks after the second stage of the surgery in order to fabricate a single crown. A definitive full-zirconia crown (yttria-stabilized zirconium oxide) with an angulated screw channel (NobelProcera FCZ Implant Crown, NobelBiocare AB) was manufactured in the determined colour at a centralized milling facility (NobelProcera Service Center, Mahwah, NJ, USA) a...
All patients referred to the Department of Oral and Maxillofacial Surgery (University of Groningen, University Medical Hospital), from January 2016 to July 2017, for single-tooth implant therapy in the maxillary and mandibular posterior region were considered for inclusion. The following inclusion criteria were applied:
One failing first or second molar in the maxilla or mandible;
Sufficient bon...
Implant placement and loading protocols are changing [1]. There is a growing tendency to place single tooth implants immediately after the extraction of a failing tooth, especially in the maxillary aesthetic region, and preferably combined with immediate provisionalization [2,3,4,5,6]. This tendency is related to evolving society factors, including more demanding patients and a wish for direct tre...
There is a growing tendency to place single tooth implants immediately after extracting a failing tooth in the posterior region. The aim of this prospective case series pilot study was to evaluate immediate implant placement in molar post-extraction sites during a 1-year follow-up period.
Fifteen consecutive patients with a single failing molar in the maxilla or mandible, and presenting enough bo...
Fig. 2. Intraoral radiograph of an immediately placed post-extractive dental implant with a full contour zirconia restoration after 1 year (same patient as in Fig. 1)
Fig. 2. Intraoral radiograph of an immediately placed post-extractive dental implant with a full contour zirconia restoration after 1 year (same patient as in Fig. 1)
Fig. 1. Pre-operative panoramic radiograph of a failing molar in position 36
Fig. 1. Pre-operative panoramic radiograph of a failing molar in position 36
 Agreement percentage (n = 11)Presence of shame0.0Self-confidence has decreased0.0Evades eating with the implant9.1The ability to chew has decreased0.0Implant influences speech0.0Implant influences taste0.0Not satisfied with the colour of the crown0.0Not satisfied with the form of the crown0.0Not satisfied with the colour of the mucosa around the crown0.0Not satisfied with the form of the muc...
Bone change (mm)n = 11mean (SD)− 0.17 mm (0.73)> − 2.0 to − 1.51 (9.1)> − 1.5 to − 1.00 (0.0)> − 1.0 to − 0.52 (18.2)> − 0.5 to 0.04 (36.4)> 0.0 to 0.52 (18.2)> 0.5 to 1.02 (18.2)Table 4 Mean value, standard deviation, and frequency distribution (percentages) of marginal bone change between 1 month after restoration placement (T1) and 1 year in ...
Bone level (mm)n = 15Mean (SD)− 0.94 mm (0.54)> − 2.5 to − 2.01 (6.7)> − 2.0 to − 1.52 (13.3)> − 1.5 to − 1.04 (26.7)> − 1.0 to − 0.55 (33.3)> − 0.5 to 0.03 (20.0)Table 3 Mean value, standard deviation, and frequency distribution (percentages) of marginal bone level at 1 month after restoration placement (T1)
 T1 (n = 15)T12 (n = 11)Plaque indexScore 0, 15 (100%)Score 0, 11 (100%)Calculus indexScore 0, 15 (100%)Score 0, 11 (100%)Gingival indexScore 0, 15 (100%)Score 0, 11 (100%)Bleeding indexScore 0, 15 (100%)Score 0, 10 (91%)Score 1, 1 (9%)Probing depth in mm (sd)2.0 (0.9)1.9 (0.8)Table 2 Frequencies and percentages of plaque index scores (possible score 0–3), calculus index scores (possibl...
Mean age in years (sd, minimum-maximum)57 (6.6, 44–67)Gender (number male/female)6/9Reason of failure (severe caries/crown fracture/root fracture)3/6/6Implant position (maxilla/mandible)7/8Implant position (in between teeth/no tooth distally)11/4Table 1 Baseline characteristics of the study group
Meijer, H.J.A., Raghoebar, G.M. Immediate implant placement in molar extraction sites: a 1-year prospective case series pilot study. Int J Implant Dent 6, 3 (2020). https://doi.org/10.1186/s40729-019-0201-7
Download citation
Received: 29 October 2019
Accepted: 11 December 2019
Published: 12 February 2020
DOI: https://doi.org/10.1186/s40729-019-0201-7
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were m...
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This clinical study was conducted in accordance with the World Medical Association Declaration of Helsinki (version VI, 2002). The Medical Ethical Committee of the University Medical Center Groningen considered this case series study not subject to the Medical Research Involving Human Subjects Act (Number M15.184100). The study was registered at the Netherlands Trial Register (Number NL8117). Afte...
Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, PO Box 30.001, NL-9700 RB, Groningen, The Netherlands
Henny J. A. Meijer & Gerry M. Raghoebar
Department of Implant Dentistry, University Medical Center Groningen, Groningen, The Netherlands
Henny J. A. Meijer
You can also search for this author in PubMed Google Scholar
You can also search for this author in...
An unrestricted grant from Nobel Biocare Services AG funded the 1-year clinical study; implant materials were provided (study code: 2015-1365).
Tallarico M, Xhanari E, Pisano M, Gatti F, Meloni SM. Molar replacement with 7 mm-wide diameter implants: to place the implant immediately or to wait 4 months after socket preservation? 1 year after loading results from a randomised controlled trial. Eur J Oral Implantol. 2017;10:169–78.
Checchi V, Felice P, Zucchelli G, Barausse C, Piattelli M, Pistilli R, Grandi G, Esposito M. Wide diameter i...
Hamouda NI, Mourad SI, El-Kenawy MH, Maria OM. Immediate implant placement into fresh extraction socket in the mandibular molar sites: a preliminary study of a modified insertion technique. Clin Implant Dent Relat Res. 2015;17(Suppl 1):e107–16. https://doi.org/10.1111/cid.12135.
Demircan S, Çankaya AB. Is immediate implant placement possible in the maxillary molar area? An anatomical study. Qu...
Gallucci GO, Hamilton A, Zhou W, Buser D, Chen S. Implant placement and loading protocols in partially edentulous patients: a systematic review. Clin Oral Implants Res. 2018;29(Suppl 16):106–34. https://doi.org/10.1111/clr.13276.
Slagter KW, Den Hartog L, Bakker NA, Vissink A, Meijer HJA, Raghoebar GM. Immediate placement of dental implants in the esthetic zone: a systematic review and pooled a...
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Within the limitations of this study, it has been demonstrated that immediate placement of regular diameter implants in molar post-extraction sites of maxilla and mandible resulted in a high implant failure rate during a 1-year follow-up period.
In an attempt to incorporate the concept of patient engagement, this study investigated the patients’ satisfaction with the rehabilitated posterior region by assessing specific patient-centred outcomes. This was done by the patients filling out the established questionnaire 1 year after restoration placement [26, 27]. All the questioned outcome measures showed high patient satisfaction which is...
The mean marginal bone level was 0.94 mm below the neck of the implant at 1 month after restoration placement (T1). The optimal position of the peri-implant bone after a maturation period should be at the same level as the neck of the implant. This means that part of the biological width of the present study, which is acting as a barrier, was in contact with the implant surface roughness and w...
Immediate placement of regular diameter implants in molar post-extraction sites of the maxilla and mandible resulted in a high implant failure rate during a 1-year follow-up period.
The implant survival rate was 73.3% after 1Â year in function. The performance of immediate placements in post-extraction sites was also analysed in the Cafiero et al., Atieh et al., Tallarico et al., and Checchi et a...
All 15 consecutive patients eligible to join the study on the basis of the inclusion and exclusion criteria agreed to participate in this study. The patient characteristics are depicted in Table 1. All implant-supported restorations had natural antagonistic teeth. Four of the 15 patients treated had a mobile implant, which had to be removed (in two patients 3 months after crown placement and in...
Radiographs were taken and evaluated 1 month and 12 months after restoration placement using a parallel technique, with an X-ray holder for periapical radiographs. They were analysed using a specially designed computer software to perform linear measurements on digital radiographs. The calibration was carried out in the vertical plane of each radiograph by using the known distance of the implan...
An impression was made at implant level 2Â weeks after the second stage of the surgery in order to fabricate a single crown. A definitive full-zirconia crown (yttria-stabilized zirconium oxide) with an angulated screw channel (NobelProcera FCZ Implant Crown, NobelBiocare AB) was manufactured in the determined colour at a centralized milling facility (NobelProcera Service Center, Mahwah, NJ, USA) a...
All patients referred to the Department of Oral and Maxillofacial Surgery (University of Groningen, University Medical Hospital), from January 2016 to July 2017, for single-tooth implant therapy in the maxillary and mandibular posterior region were considered for inclusion. The following inclusion criteria were applied:
One failing first or second molar in the maxilla or mandible;
Sufficient bon...
Implant placement and loading protocols are changing [1]. There is a growing tendency to place single tooth implants immediately after the extraction of a failing tooth, especially in the maxillary aesthetic region, and preferably combined with immediate provisionalization [2,3,4,5,6]. This tendency is related to evolving society factors, including more demanding patients and a wish for direct tre...
There is a growing tendency to place single tooth implants immediately after extracting a failing tooth in the posterior region. The aim of this prospective case series pilot study was to evaluate immediate implant placement in molar post-extraction sites during a 1-year follow-up period.
Fifteen consecutive patients with a single failing molar in the maxilla or mandible, and presenting enough bo...
RFs (log rank, p = 0.006)
Fig. 2. The cumulative survival rates for the different RF groups revealing a significant difference for patients without any and patients with local and systemic RFs (log rank, p = 0.006)
Fig. 1. On Kaplan-Meier survival estimates, the cumulative survival rate was 91.5%
Fig. 1. On Kaplan-Meier survival estimates, the cumulative survival rate was 91.5%
Region
Systemic RF
Local RF
Immediate procedure
Bone grafting
Time of failure (months...
Systemic RF
No. of implants (n = 31)
No. of patients (n = 14)
Local RF
No. of implants (n = 100)
...
Saridakis, S.K., Wagner, W. & Noelken, R. Retrospective cohort study of a tapered implant with high primary stability in patients with local and systemic risk factors—7-year data.
Int J Implant Dent 4, 41 (2018). https://doi.org/10.1186/s40729-018-0151-5
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Received: 20 May 2018
Accepted: 24 October 2018
Published: 17 December 2018
DOI: https://doi.org/10...
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were m...
This article contains data obtained during follow-up in a cohort of patients treated with a CE-certified implant in a University Medical Center. Since the product is already approved in accordance with the German Medical Devices Act, no additional ethics approval was not required for treatment. All procedures performed in studies involving human participants were in accordance with the ethical sta...
Department of Oral and Maxillofacial Surgery – Plastic Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Augustusplatz 2, 55131, Mainz, Germany
Sotirios Konstantinos Saridakis, Wilfried Wagner & Robert Noelken
Private Practice for Oral Surgery, Lindau/Lake Constance, Germany
Robert Noelken
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PubMed Go...
Not applicable
The work was supported by the Clinic of Oral and Maxillofacial Surgery, University Medical Center, Mainz.
The dataset supporting the conclusions of this article is partially included within the article. The SPSS data can be given on demand of the editor.
Schropp L, Isidor F, Kostopoulos L, Wenzel A. Patient experience of, and satisfaction with, delayed-immediate vs delayed single-tooth implant placement. Clin Oral Implants Res. 2004;15:498–503.
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Hultin M, Gustafsson A, Hallstrom H, Johansson LA, Ekfeldt A, Klinge B. Microbiological findings and host response in patients with periimplantitis. Clin Oral Implants Res. 2002;13:349–58.
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Chrcanovic BR, Albrektsson T, Wennerberg A. Diabetes and oral implant failure: a systematic review. J Dent Res. 2014;93(9):859–67.
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Ortega-Martinez J, Perez-Pascual T, Mareque-Bueno S, Hernandez-Alfaro F, Ferres-Padro E. Immediate implants following tooth extraction. A systemic review. Med Oral Patol Oral Cir Bucal. 2012;17(2):e251â€...
U.S. Census Bureau, 2012 Population Estimates and 2014 National Projections. [Zitiert:18.12.2014]. https://www.census.gov/data/tables/2014/demo/popproj/2014-summary-tables.html.
Ikebe K, Wada M, Kagawa R, Maeda Y. Is old age a risk factor for dental implants? Jpn Dent Sci Rev. 2009;45:59–64.
Hu SC, Lan CE. High-glucose environment disturbs the physiologic functions of keratinocytes: focusing o...
This study was based on the recruitment of a quite heterogeneous group of patients treated with NobelActive implants, for the purpose of investigating the influence of local and systemic risk factors on implant survival and marginal bone levels. It can be considered that the presence of local or systemic risk factors does not influence implant survival whereas the combination of local and systemic...
A major weakness of the study is the relative small size of the group with systemic RFs (14 implants by 6 patients) as well as of the group with systematic and local RFs (17 implants by 6 patients). Because of the relative small size of the sample, this study can provide the basis for further investigations based on larger patient samples.
The survival rate for 93 implants in 45 patients with no RFs was 94.8%. Moraschini et al. [44] have exhibited in their systematic review, based on 7711 implants, similar SRs with cumulative mean values of 94.6%. Moreover, in the subcohort of our study, by 44 of the above 93, implants were performed immediate procedures (25 immediate implantations, 35 immediate restorations, 16 both of them) so the...
In one patient with three implants and long intake of corticosteroids against rheumatoid arthritis (7.5 mg prednisolone per day for at least 2 years), no complication was detected in our study. Long-term use of corticosteroids can also lead to implant failures, according to Wood and Vermilyea [34] by modifying the patient’s response to bacterial infection [35], but at the present time, there i...
Most implant studies deal only with local risk factors, although the existence of systemic risk factors plays a significant role to the implant survival. We use the NobelActive dental implant in this study in order to investigate if this promising implant with the special design could achieve better survival rates in difficult situations with several risk factors. The present study revealed no sta...
Regarding the implant shoulder level, the average interproximal marginal bone level was − 0.49 ± 0.83 mm (range, 0 to − 3.3 mm) at the mesial aspect and − 0.51 ± 0.82 mm (range, 0 to − 3.9 mm) at the distal aspect of the implants.
When the marginal bone level was considered as a function of time, there was no strict correlation between the marginal bone status and th...
Ninety-eight patients with 207 implants complied with the treatment protocol attended the follow-up.
During the follow-up period, 15 implants failed in 12 patients. Age and gender were not correlated with a lower implant survival. The implant losses occurred in a time range between 0.5 and 39 months following implant placement (mean 7.3 ± 11.1 months). The reasons for implant failure were ...
Subpopulations within the study group (immediate vs. delayed placement) were compared using the Wilcoxon-Mann-Whitney non-parametric U test. The reported p values were two sided. All calculations were carried out using SPSS for Mac, Version 22 (SPSS Inc., Chicago, IL, USA).
Preservation of all alveolar socket walls via longitudinal extraction after periotomy avoiding oro-vestibular luxation.
Meticulous cleaning of the extraction site.
Placement of rather long implants that allow for a high level of primary stability.
Implant dimensions were as follows: implant length 8.5Â mm, 24 implants; 10Â mm, 6 implants; 11.5Â mm, 64 implants; 13Â mm, 80 implants; 15Â mm, 31 i...
These patients received a total of 207 NobelActive implants (Nobel Biocare, Zurich, Switzerland) placed by two experienced surgeons. Between November 2011 and February 2015, 188 implants were placed in the maxilla, and 19 implants in the mandible. All implant placement procedures were conducted at the Department of Oral and Maxillofacial Surgery of the University Medical Center, Mainz, Germany. Fi...
One hundred and ten patients were invited for follow-up evaluation. All patients were treated in the period from 10/2008 to 02/2015 in the Clinic of Oral and Maxillofacial Surgery, University Medical Center Mainz. Inclusion criteria were as follows: implant placement of a NobelActive implant, study subjects over 18Â years old, residual bone dimension in the edentulous region of at least 5Â mm in h...
Primary stability is a prerequisite for successful osseointegration and remains the most significant factor for the survival of dental implants [16]. Therefore, current research focuses on amelioration of existing augmentation techniques and materials or on the development of new implants with self-tapping properties for improving bone contact as well for increasing primary stability.
The aim of ...
Based on published demographic data, the median age of the world population constantly increases [1]. This has led to an increase in the number of dental implants inserted in senior individuals with local and systemic risk factors [2]. Nevertheless, despite numerous studies having been conducted on this topic, the results remain controversial, almost 50Â years after the first dental implant placem...
This retrospective study examined the mid- to long-term clinical and radiographic performance of a tapered implant in various treatment protocols in patients with local and systemic risk factors (RFs).
Two hundred seven NobelActive implants were inserted in 98 patients in the period from 10/2008 to 02/2015. The subdivision of the cohort was defined by local (n = 40), systemic (n = 6), loc...