In addition to socio-demographic information (age, gender and education level) and body mass index (BMI: weight/height2), all participants received a full-mouth periodontal examination by a trained periodontist (PA) as previously described15. Full-mouth clinical periodontal measurements (i.e., six sites per tooth) from each participant including gingival pocket depth (PD), clinical attachment level (CAL), dental plaque accumulation, and gingival bleeding19 were obtained just before OnabotA treatment was initiated using a calibrated University of North Carolina periodontal probe (UNC15, Hu-Friedy, Chicago, IL, USA). The presence of periodontitis was established when ≥ 2 interproximal sites with CAL ≥ 3 mm and ≥ 2 interproximal sites with PD ≥ 4 mm (not on the same tooth) or 1 site with PD ≥ 5 mm were present20. Additionally, we calculated a measure of periodontitis activity, the periodontal inflamed surface area (PISA), which reflects the surface area of bleeding pocket epithelium in mm221. PISA was calculated as follows: (1) with the mean CAL and gingival recession we obtained the periodontal epithelial surface area (PESA) for each tooth22; (2) the PESA value multiplied by the number of sites with bleeding upon probing results in the PISA for an specific tooth; (3) Full-mouth PISA is calculated for each participant (in mm2) by the sum of the PISAs for each tooth.

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