Influence of gender on periodontal outcomes: A retrospective analysis of eight randomized clinical trials.

AIMS: To explore the influence of gender on periodontal treatment outcomes in a dataset of eight RCTs conducted in Brazil, United States, and Germany. METHODS: Clinical parameters were compared between men and women with stages III/IV grades B/C generalized periodontitis at baseline and 1-year post-therapy, including scaling and root planing with or without antibiotics. RESULTS: Data from 1042 patients were analyzed. Men presented a tendency towards higher probing depth (p = .07, effect size = 0.11) and clinical attachment level (CAL) than women at baseline (p = .01, effect size = 0.16). Males also presented statistically significantly lower CAL gain at sites with CAL of 4-6 mm at 1-year post-therapy (p = .001, effect size = 0.20). Among patients with Grade B periodontitis who took antibiotics, a higher frequency of women achieved the endpoint for treatment (i.e., ≤4 sites PD ≥5 mm) at 1 year than men (p < .05, effect size = 0.12). CONCLUSION: Men enrolled in RCTs showed a slightly inferior clinical response to periodontal therapy in a limited number of sub-analyses when compared to women. These small differences did not appear to be clinically relevant. Although gender did not dictate the clinical response to periodontal treatment in this population, our findings suggest that future research should continue to explore this topic.

Domains, competences and learning outcomes for undergraduate education in periodontology.

AIM: This review is intended to adapt the current conceptual framework in dental education based on four domains to propose a set of competences, learning outcomes and methods of teaching, learning and assessment for undergraduate education in periodontology. REVIEW: Based on the current framework of competences and learning outcomes recommended by the Association for Dental Education in Europe (ADEE), undergraduate education in periodontology has been updated using the classification and clinical practice guidelines for the diagnosis and treatment of periodontal and peri-implant diseases. CONCLUSIONS: Specific learning outcomes have been proposed within each competence area, that is in Domain I (n = 10), Domain II (n = 13), Domain III (n = 33) and Domain IV (n = 12). Teaching methods and learning activities based on the different dimensions of the cognitive process have been proposed. Additionally, 10 key learning outcomes have been proposed as exit outcomes, which implies their accomplishment within the final assessment of any graduating student.

Influence of fixed orthodontic steel retainers on gingival health and recessions of mandibular anterior teeth in an intact periodontium - a randomized, clinical controlled trial.

OBJECTIVE: Aim of this randomized clinical controlled trial was to evaluate the influence of fixed orthodontic steel retainers on gingival health and recessions of mandibular anterior teeth. MATERIALS AND METHODS: After end of the orthodontic treatment, patients were randomly assigned into the test (fixed steel retainer) or control group (modified removable vacuum-formed retainer). Periodontal parameters (periodontal probing depth: PPD; recession: REC; bleeding on probing: BOP) as well as plaque and gingival index were assessed on mandibular anterior teeth directly before attaching/handing over the retainer (baseline: BL), 6 and 12 months after orthodontic treatment. RESULTS: 37 patients (test: n = 15, mean age: 16.1±4.2 years; control: n = 17, mean age: 17.1±5.4 years) completed the study. REC and PPD failed to show significant pairwise differences. The number of patients showing gingival health in the area of the mandibular anterior teeth (test: BL n = 10, 6 months n = 9, 12 months n = 11; control: BL n = 10, 6 months n = 16, 12 months n = 15) revealed a significant difference for the intra-group comparison between BL and 6 months in the control group (p = 0.043). The inter-group comparisons failed to show significant differences. CONCLUSION: Young orthodontically treated patients with fixed steel retainers show in 73.3% healthy gingival conditions after one year which are comparable to the control group (88.2%). Gingival recessions were in a clinically non-relevant range at any time of the examination. CLINICAL TRIAL NUMBER: DRKS00016710.

A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis: Airleaf.

New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf™; NCT05238675) assessing the efficacy and safety of a novel CatC inhibitor, BI 1291583, in adult patients with bronchiectasis. This multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study has a screening period of at least 6 weeks, a treatment period of 24-48 weeks and a follow-up period of 4 weeks. ∼240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1 mg once daily, 2.5 mg once daily or 5 mg once daily in a 2:1:1:2 ratio, stratified by Pseudomonas aeruginosa infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose-response relationship for the three oral doses of BI 1291583 versus placebo on time to first pulmonary exacerbation up to Week 48 (the primary end-point). Efficacy will be assessed using exacerbations, patient-reported outcomes, measures of symptoms, sputum neutrophil elastase activity and pulmonary function testing. Safety assessment will include adverse event reporting, physical examination, monitoring of vital signs, safety laboratory parameters, 12-lead electrocardiogram, and periodontal and dermatological assessments. If efficacy and safety are demonstrated, results will support further investigation of BI 1291583 in phase 3 trials.

Clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis stage and grade: An exploratory sub-analysis of the ABPARO trial.

AIM: Assessment of treatment response after systemic amoxicillin/metronidazole adjunctive to subgingival instrumentation (SI) according to stages and grades of the 2018 classification of periodontal diseases. MATERIALS AND METHODS: We carried out exploratory re-analysis of the placebo-controlled, multi-centre ABPARO trial (52; 45/60 years of age; 205 males, 114 active smokers). Patients were randomized to SI with systemic amoxicillin 500 mg/metronidazole 400 mg (three times a day for 7 days, n = 205; ANTI) or placebo (n = 200; PLAC) and maintenance therapy every 3 months. Patients were reclassified according to the 2018 classification (stage/extent/grade). Treatment effect was the percentage of sites per patient with new attachment loss ≥1.3 mm (PSAL ≥ 1.3 mm) at 27.5 months post-baseline/randomization. RESULTS: All patients were assigned according to the stage (n = 49 localized stage III, n = 206 generalized stage III, n = 150 stage IV). Because of missing radiographs, only 222 patients were assigned to grades (n = 73 B, n = 149 C). Treatment (PLAC/ANTI) resulted in PSAL ≥ 1.3 mm (median; lower/upper quartile) in localized stage III (PLAC: 5.7; 3.3/8.4% vs. ANTI: 4.9; 3.0/8.3%; p = .749), generalized stage III (8.0; 4.5/14.3% vs. 4.7; 2.4/9.0%; p < .001), stage IV (8.5; 5.1/14.4% vs. 5.7; 3.3/10.6%; p = .008), grade B (4.4; 2.4/6.7% vs. 3.6; 1.9/4.7%; p = .151) and grade C (9.4; 5.3/14.3% vs. 4.8; 2.5/9.4%; p < .001). CONCLUSIONS: In generalized periodontitis stage III/grade C, a clinically relevant lower percentage of disease progression after adjunctive systemic amoxicillin/metronidazole was observed compared to placebo (PLAC: 9.7; 5.8/14.3% vs. ANTI: 4.7; 2.4/9.0%; p < .001).

Long-term changes in the subgingival microbiota in patients with stage III-IV periodontitis treated by mechanical therapy and adjunctive systemic antibiotics: A secondary analysis of a randomized controlled trial.

AIM: To explore whether adjunctive antibiotics can relevantly influence long-term microbiota changes in stage III-IV periodontitis patients. MATERIALS AND METHODS: This is a secondary analysis of a randomized clinical trial on periodontal therapy with adjunctive 500 mg amoxicillin and 400 mg metronidazole or placebo thrice daily for 7 days. Subgingival plaque samples were taken before and 2, 8, 14 and 26 months after mechanical therapy. The V4-hypervariable region of the 16S rRNA gene was sequenced with Illumina MiSeq 250 base pair paired-end reads. Changes at the ribosomal sequence variant (RSV) level, diversity and subgingival-microbial dysbiosis index (SMDI) were explored with a negative binomial regression model and non-parametric tests. RESULTS: Overall, 50.2% of all raw reads summed up to 72 RSVs (3.0%) that were generated from 163 stage III-IV periodontitis patients. Of those, 16 RSVs, including Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans, changed significantly over 26 months because of adjunctive systemic antibiotics. SMDI decreased significantly more in the antibiotic group at all timepoints, whereas the 2-month differences in alpha and beta diversity between groups were not significant at 8 and 14 months, respectively. CONCLUSIONS: Mechanical periodontal therapy with adjunctive antibiotics induced a relevant and long-term sustainable change towards an oral microbiome more associated with oral health.

Long-term stability of infrabony defects treated with enamel matrix derivative alone: A retrospective two-centre cohort study.

AIM: To assess the long-term stability of attachment gain in infrabony defects (IBDs) 10 years after regenerative treatment with an enamel matrix derivative (EMD) alone. MATERIALS AND METHODS: Two centres (Frankfurt [F] and Heidelberg [HD]) invited patients for re-examination 120 ± 12 months after regenerative therapy. Re-examination included clinical examination (periodontal probing depths (PPD), vertical clinical attachment level (CAL), plaque index (PlI), gingival index (GI), plaque control record, gingival bleeding index and periodontal risk assessment) and review of patient charts (number of supportive periodontal care [SPC] visits). RESULTS: Both centres included 52 patients (29 female; median baseline age: 52.0 years; lower/upper quartile: 45.0/58.8 years; eight smokers), each contributing one IBD. Nine teeth were lost. For the remaining 43 teeth, regenerative therapy showed significant CAL gain after 1 year (3.0; 2.0/4.4 mm; p < .001) and 10 years (3.0; 1.5/4.1 mm; p < .001) during which CAL remained stable (-0.5; -1.0/1.0 mm; p = 1.000) after an average SPC of 9 years. Mixed-model regression analyses revealed a positive association of CAL gain from 1 to 10 years with CAL 12 months post operation (logistic: p = .01) as well as a higher probability for CAL loss with an increasing vertical extent of a three-walled defect component (linear: p = .008). Cox proportional hazard analysis showed a positive association between PlI after 12 months and tooth loss (p = .046). CONCLUSION: Regenerative therapy of IBDs showed stable results over 9 years. CAL gain is associated with CAL after 12 months and decreasing initial defect depth in a three-walled defect morphology. Tooth loss is associated with PlI 12 months post operation. CLINICAL TRIAL NUMBER: DRKS00021148 (URL: https://drks.de).

The influence of interradicular anatomy on the predictability of periodontal regenerative therapy of furcation defects: a retrospective, multicenter clinical study.

BACKGROUND: The relationship between the anatomy of the interradicular space and success in regenerative therapy of furcation defects is discussed in this paper. The goal of this retrospective, multicenter clinical study is to clinically evaluate the relationship between the interradicular conformation and regenerative therapy success with the use of a novel measurement method. METHODS: One hundred thirty-eight radiographs of mandibular molars with furcation defects that had been treated with regenerative therapy were collected from six clinical centers. Data on the type of therapy and clinical parameters before and after treatment (follow-up of at least 12 months) were collected. The radiographs (before surgery and at least 12 months postoperatively) were measured with a visual evaluation method by a blind operator using graphics software. RESULTS: Success, defined as a reduction in horizontal and vertical furcation involvement, decrease in probing depths, and increase in clinical attachment level, was statistically assessed on 138 regenerated molars sites and were related to clinical variables such as age, sex, center, and treatment. No correlation was found between success in regenerative therapy and the conformation of the interradicular space, measured with a visual ratio method and a standard linear measurement. At the univariate analysis, the parameters that had a correlation with success were center, extent of furcation involvement, treatment, and sex. The use of enamel matrix derivative (EMD) seemed to be the most favorable therapy, with increase in CAL gain and reduction of vertical or horizontal furcation involvement. CONCLUSIONS: The regenerative outcome was not significantly influenced by the anatomy of furcation. The center, the degree of furcation involvement, sex, and treatment (EMD) were significantly associated with higher success of periodontal regeneration.

In vitro efficacy of non-surgical and surgical implant surface decontamination methods in three different defect configurations in the presence or absence of a suprastructure.

OBJECTIVES: Analysis of the in vitro efficacy of non-surgical and surgical dental implant surface decontamination with or without suprastructure. MATERIALS AND METHODS: Three hundred and sixty implants were dipped in indelible red and distributed to 30°, 60°, or 90° angulated bone defect models. One hundred and twenty implants were used for each bone defect, 40 of which were assigned to a decontamination method (CUR: curette; SOSC: soundscaler; APA: air powder abrasion). Of these, 20 were subjected to a simulated non-surgical (NST) or surgical treatment (ST), with/without mucosa mask, of which 10 were carried out with (S+) or without (S-) suprastructure. Uncleaned implant surface was assessed by both-sided implant surface photography. Surface morphology changes were analyzed using scanning electron microscopy (SEM). RESULTS: Cleaning efficacy was significantly better within NST if the suprastructure was removed (p < 0.001). No significant difference was found within ST (p = 0.304). Overall, cleaning efficacy in the order APA > SOSC>CUR decreased significantly (p < 0.0001) for both S+ and S- in NST as well as ST. Separated by NST/ST, S+/S-, defect angulation and decontamination method, only isolated significant differences in cleaning efficacy were present. Linear regression analysis revealed significant associations of remnants with the treatment approach, decontamination method, and defect angle (p < 0.0001). SEM micrographs showed serious surface damage after use of CUR and SOSC. CONCLUSIONS: Suprastructure removal is an additional option to improve cleaning efficacy of non-surgical implant surface decontamination in this in vitro model.

Oral health-related quality of life and patient-reported outcome measures after 10 years of supportive periodontal care.

OBJECTIVE: The aim of this retrospective study was to evaluate the oral health-related quality of life (oHRQoL) and patient-reported outcome measures (PROMs) after 10 years of supportive periodontal care (SPC). MATERIAL AND METHODS: Patients were re-examined 120±12 months after active periodontal therapy. Dental and periodontal status and oHRQoL by completing Oral Health Impact Profile-G49 (OHIP-G49) and PROMs by marking a visual analogue scale (VAS) for self-perceived esthetics (VASe), chewing function (VASc), and hygiene ability (VASh) were assessed. Patient- and tooth-related factors (age, insurance status, number of SPC, compliance, change of therapist, smoking, tooth loss, need for surgery or antibiotic intake, bleeding on probing (BOP), periodontal inflamed surface area) influencing oHRQoL and PROMs were evaluated. RESULTS: One hundred eight periodontally compromised patients (59 female, mean age 65.4±10.7 years) lost 135 teeth during 10 years of SPC. At re-examination, 1.8% of all sites showed PPD ≥6mm. The mean OHIP-G49 sum score was 17.6±18.5, and VAS resulted in 76.0±22.5 (VASe), 86.3±16.3 (VASc), and 79.8±15.8 (VASh). Linear regression analyses identified a positive correlation with oHRQoL and/or PROMs for private insurance status (OHIP-G49, p=0.015, R2=0.204; VASc, p=0.005, R2=0.084; VASh, p=0.012, R2=0.222) and compliance to SPC (VASe, p=0.032; R2=0.204), as well as a negative correlation for active smoking (VASc, p=0.012, R2=0.084), increased BOP (VASh, p=0.029, R2=0.222) at the start of SPC, and number of lost molars (VASh, p=0.008, R2=0.222). CONCLUSION: It is realistic to obtain satisfactory oHRQoL and PROM values in most of the patients after 10 years of SPC. The identified factors may help to predict patient satisfaction in the long-term course of therapy. CLINICAL RELEVANCE: Systematic therapy of periodontally compromised patients provides values for oHRQoL and PROMs in a favorable range 10 years after therapy. This should encourage dentists to implement SPC in their daily routine. CLINICAL TRIAL NUMBER: NCT03048045.

Additional benefit of systemic antibiotics in subgingival instrumentation of stage III and IV periodontitis with Aggregatibacter actinomycetemcomitans: A retrospective analysis.

AIM: To evaluate subgingival instrumentation (SI) in periodontitis stage III and IV, grade B and C with systemic antibiotics (AB) only after detection of Aggregatibacter actinomycetemcomitans. MATERIALS AND METHODS: Patients of the Department of Periodontology of Goethe University Frankfurt/Germany were screened for microbiological testing between 2008 and 2018. All patients with aggressive and generalized severe chronic periodontitis were tested. In case of positive subgingival A. actinomycetemcomitans tests, SI was combined with AB; in all other cases it was not (nAB). Clinical examinations were performed before (T0), 12.4 (9.4/15.1) weeks after SI (T1), and at the last supportive periodontal care (T2; 3.1 [1.4/5.5] years after T1). Results at T1/T2 were assessed as "treat-to-target" endpoint (≤4 sites with probing pocket depths ≥5 mm). RESULTS: Four-hundred and twenty-five patients (280 stage III/145 stage IV, 95 grade B/330 grade C) provided complete data (AB 144/nAB 281) for T0 and T1, and 332 (AB 121/nAB 211) for T2. At T1/T2, AB resulted in 53 (37%)/76 (63%) patients with "treat-to-target" endpoint, and nAB in 76 (27%)/91 (43%) (p = .038/.001). CONCLUSIONS: In periodontitis stage III and IV, grade B and C with subgingival A. actinomycetemcomitans infection, SI with AB resulted in higher rate of "treat-to-target" endpoint than exclusive SI in patients without the infection.

Esthetic and clinical outcomes after immediate placement and restoration: Comparison of two implant systems in the anterior maxilla-A cross-sectional study.

AIM: To assess the esthetic and clinical performance of a novel self-tapping implant system for single-tooth restorations in the esthetic zone after immediate placement and provisionalization. MATERIALS AND METHODS: This cross-sectional study included 52 patients contributing a total of 52 immediately placed and restored implants with ≥12 months after functional loading, comparing two different implant systems: Straumann® BLX (Institut Straumann AG, Basel, Switzerland; 25 patients) and Ankylos® (Dentsply Sirona, Hanau, Germany; 27 patients). As the primary outcome measure, peri-implant tissue esthetics were assessed by means of pink esthetics score (PES) rated by three independent clinicians. Moreover, as secondary outcome measures, the peri-implant tissue health was assessed by means of bleeding on probing, probing depth, and suppuration. Apart from that, the modified plaque index, keratinized mucosa width, and the presence of mucosal recessions were also assessed. When clinical signs suggested the possibility of peri-implantitis, radiographs were indicated to assess progressive bone loss. RESULTS: The mean PES ratings were 12.10 ± 1.10 for Ankylos versus 11.2 ± 1.86 for BLX, both achieving good esthetic results without significant differences (p = 0.143). There were no differences among most clinical parameters (plaque, bleeding on probing, probing depth, peri-implant mucosal recession), although peri-implant mucositis was present in one-third of the cases. The inter-rater agreement on esthetics was not significant (p < 0.250). CONCLUSION: Within the limitations of the present study, it was concluded that the use of either BLX or Ankylos implant systems was associated to comparable peri-implant health and good pink esthetic outcomes during immediate implantation and restoration protocols, for at least 12 months.

Development and international validation of logistic regression and machine-learning models for the prediction of 10-year molar loss.

AIM: To develop and validate models based on logistic regression and artificial intelligence for prognostic prediction of molar survival in periodontally affected patients. MATERIALS AND METHODS: Clinical and radiographic data from four different centres across four continents (two in Europe, one in the United States, and one in China) including 515 patients and 3157 molars were collected and used to train and test different types of machine-learning algorithms for their prognostic ability of molar loss over 10 years. The following models were trained: logistic regression, support vector machine, K-nearest neighbours, decision tree, random forest, artificial neural network, gradient boosting, and naive Bayes. In addition, different models were aggregated by means of the ensembled stacking method. The primary outcome of the study was related to the prediction of overall molar loss (MLO) in patients after active periodontal treatment. RESULTS: The general performance in the external validation settings (aggregating three cohorts) revealed that the ensembled model, which combined neural network and logistic regression, showed the best performance among the different models for the prediction of MLO with an area under the curve (AUC) = 0.726. The neural network model showed the best AUC of 0.724 for the prediction of periodontitis-related molar loss. In addition, the ensembled model showed the best calibration performance. CONCLUSIONS: Through a multi-centre collaboration, both prognostic models for the prediction of molar loss were developed and externally validated. The ensembled model showed the best performance in terms of both discrimination and validation, and it is made freely available to clinicians for widespread use in clinical practice.

Common practices of dental implants maintenance among dental hygiene professionals in Israel and Germany.

OBJECTIVE: The aim of this study was to assess the common practices of dental implant maintenance among dental hygiene professionals (DHP) in Israel (IL) and Germany (GE). METHODS: An online questionnaire was developed by the Periodontology Departments of Tel Aviv (IL) and Frankfurt University (GE) to address demographics, training, prevention and treatment of peri-implant diseases. The questionnaire was distributed by DHP associations via social media. RESULTS: The responses of 376 DHPs (IL: 169; GE: 207) were analysed. Most participants were female (IL: 168/99%; GE: 203/98%), had received education (IL: 179/97%; GE: 207/97%) and were working in their home countries (IL: 182/99%; GE: 211/99%). Peri-implant probing was not performed by 22% of DHPs in IL and 5% in GE. Of the DHPs who used probes, 49% used metal probes in IL, while 40% used plastic probes in GE (p < 0.001). A majority of DHPs performed peri-implant instrumentation (IL: 168/99%; GE: 190/92%). Most DHPs from IL did not use devices other than hand and/or sonic/ultrasonic instruments for peri-implant cleaning (IL: 130/77%; GE 5/2%); in GE, the use of airflow (IL: 31/18%; GE: 199/96%) is popular (p < 0.001). CONCLUSIONS: Most DHPs in IL and GE perform peri-implant probing and debridement. However, there are some distinct differences between the two countries regarding the choice of instruments and treatment regimens.

Subsiding of Periodontitis in the Permanent Dentition in Individuals with Papillon-Lefèvre Syndrome through Specific Periodontal Treatment: A Systematic Review.

Papillon-Lefèvre syndrome (PLS) is a rare hereditary disease characterized by palmoplantar hyperkeratosis (PPK) and periodontitis in the primary and permanent dentition, usually resulting in edentulism in youth. Subsiding of PLS-associated periodontitis through specific therapy has occasionally been reported. We aimed to systematically assess periodontal treatment strategies that may decelerate disease progression. A systematic literature search was conducted at PubMed/LIVIVO/Ovid (Prospero registration number CRD42021223253). Clinical studies describing periodontal treatment success-defined as loss of ≤four permanent teeth because of periodontitis and the arrest of periodontitis or probing depths ≤ 5 mm-in individuals with PLS followed up for ≥24 months. Out of the 444 primarily identified studies, 12 studies reporting nine individuals were included. The timely extraction of affected or, alternatively, all primary teeth, compliance with oral hygiene instructions, supra- and subgingival debridement within frequent supportive periodontal care intervals, and-in eight patients-adjunctive systemic antibiotic therapy (mostly amoxicillin/metronidazole) effected a halt in disease progression. The suppression of Aggregatibacter actinomycetemcomitans below the detection limit was correlated with the subsiding of periodontitis. Successful controlling of PLS-associated periodontitis may be achieved if high effort and patient compliance are provided.

The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy.

Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression.

Assessment of periodontitis grade in epidemiological studies using interdental attachment loss instead of radiographic bone loss.

AIM: Comparison of grading according to radiographic bone loss (BL) or according to interdental clinical attachment loss (CAL). MATERIALS AND METHODS: In 100 periodontitis patients at the Department of Periodontology of Goethe-University Frankfurt, Germany, periodontitis grade was assigned by (i) indirect evidence using BL at the most affected tooth divided by root length and (ii) CAL at the most affected tooth divided by root length of the respective tooth type according to root length in German and Swedish cohorts. The resulting quotients were divided by age. RESULTS: Patients (age: 53.5 ± 10.4 years; 57 females; 16 smokers; no diabetes; stage: 78 III, 22 IV) were by either method assigned to grade B or C (BL: 35 B, 65 C; CAL [German]: 23 B, 77 C; [Swedish]: 29 B, 71 C). Using root length (German cohort), agreement was 76% (kappa: 0.427; fair to good/moderate agreement) and 72% (Swedish cohort; kappa: 0.359; poor/fair agreement). Molars were most frequently chosen (BL: 64%; CAL: 71%). CONCLUSIONS: Assignment of periodontitis grade by indirect evidence using BL or CAL using standard root length of the German cohort showed fair to good/moderate agreement. Thus, grade assignment by CAL may be used in epidemiologic studies where radiographs are not available.

Effect of Subgingival Instrumentation on Neutrophil Elastase and C-Reactive Protein in Grade B and C Periodontitis: Exploratory Analysis of a Prospective Cohort Study.

Background: Assessment of the effect of subgingival instrumentation (SI) on systemic inflammation in periodontitis grades B (BP) and C (CP). Methods: In this prospective cohort study, eight BP and 46 CP patients received SI. Data were collected prior to and 12 weeks after SI. Blood was sampled prior to, one day, 6, and 12 weeks after SI. Neutrophil elastase (NE), C-reactive protein (CRP), leukocyte count, lipopolysaccharide binding protein, interleukin 6 (IL-6) and IL-8 were assessed. Results: Both groups showed significant clinical improvement. NE was lower in BP than CP at baseline and 1 day after SI, while CRP was lower in BP than CP at baseline (p < 0.05). NE and CRP had a peak 1 day after SI (p < 0.05). Between-subjects effects due to CP (p = 0.042) and PISA (p = 0.005) occurred. Within-subjects NE change was confirmed and modulated by grade (p = 0.017), smoking (p = 0.029), number of teeth (p = 0.033), and PISA (p = 0.002). For CRP between-subjects effects due to BMI (p = 0.008) were seen. Within-subjects PISA modulated the change of CRP over time (p = 0.017). Conclusions: In untreated CP, NE and CRP were higher than in BP. SI results in better PPD and PISA reduction in BP than CP. Trial registration: Deutsches Register Klinischer Studien DRKS00026952 28 October 2021 registered retrospectively.

Long-Term Results after Placing Dental Implants in Patients with Papillon-Lefèvre Syndrome: Results 2.5-20 Years after Implant Insertion.

AIM: A retrospective evaluation of patients with Papillon-Lefèvre syndrome (PLS) treated with dental implants to identify factors that may influence treatment outcomes. METHODS: All PLS patients with dental implants currently registered at the Department of Periodontology, Goethe-University Frankfurt (20-38 years; mean: 29.6 years), were recruited. Five patients from three families (two pairs of siblings) with a total of 48 dental implants (inserted in different dental institutions) were included with a follow-up time of 2.5-20 years (mean: 10.4 years). RESULTS: Implant failure occurred in three patients (at least 15 implants). Nearly all patients demonstrated peri-implantitis in more or less advanced stages; 60% of patients demonstrated bone loss ≥50% around the implants. Two patients did not follow any supportive therapy. CONCLUSIONS: Implants in PLS patients who did not follow any maintenance programme had a high risk of peri-implantitis and implant loss.

Targeting Cathepsin C in PR3-ANCA Vasculitis.

BACKGROUND: The ANCA autoantigens proteinase 3 (PR3) and myeloperoxidase (MPO) are exclusively expressed by neutrophils and monocytes. ANCA-mediated activation of these cells is the key driver of the vascular injury process in ANCA-associated vasculitis (AAV), and neutrophil serine proteases (NSPs) are disease mediators. Cathepsin C (CatC) from zymogens activates the proteolytic function of NSPs, including PR3. Lack of NSP zymogen activation results in neutrophils with strongly reduced NSP proteins. METHODS: To explore AAV-relevant consequences of blocking NSP zymogen activation by CatC, we used myeloid cells from patients with Papillon-Lefèvre syndrome, a genetic deficiency of CatC, to assess NSPs and NSP-mediated endothelial cell injury. We also examined pharmacologic CatC inhibition in neutrophil-differentiated human hematopoietic stem cells, primary human umbilical vein cells, and primary glomerular microvascular endothelial cells. RESULTS: Patients with Papillon-Lefèvre syndrome showed strongly reduced NSPs in neutrophils and monocytes. Neutrophils from these patients produced a negative PR3-ANCA test, presented less PR3 on the surface of viable and apoptotic cells, and caused significantly less damage in human umbilical vein cells. These findings were recapitulated in human stem cells, in which a highly specific CatC inhibitor, but not prednisolone, reduced NSPs without affecting neutrophil differentiation, reduced membrane PR3, and diminished neutrophil activation upon PR3-ANCA but not MPO-ANCA stimulation. Compared with healthy controls, neutrophils from patients with Papillon-Lefèvre syndrome transferred less proteolytically active NSPs to glomerular microvascular endothelial cells, the cell type targeted in ANCA-induced necrotizing crescentic glomerulonephritis. Finally, both genetic CatC deficiency and pharmacologic inhibition, but not prednisolone, reduced neutrophil-induced glomerular microvascular endothelial cell damage. CONCLUSIONS: These findings may offer encouragement for clinical studies of adjunctive CatC inhibitor in patients with PR3-AAV.