Background: Peri-implant defect morphology has shown to potentially impact upon the reconstructive outcomes for the management of peri-implantitis. Given the role that defect morphology plays upon the decision-making in the treatment of peri-implantitis, the present study aimed at assessing the morphology and severity of peri-implantitis bone defects and to insight on the patient-, implant-and site-related variables associated to these. Material and Methods:A cone-beam computed tomography study was carried out to classify peri-implantitis defects according to the type of defect, number of remaining bony walls and severity according to the extension of vertical bone loss.Three major defect categories were proposed: class I-infraosseous; class II-horizontal;class III-combined of class I and II. These were then subclassified into: (a) dehiscence; (b) 2/3-wall; and (c) circumferential-type defect. According to the severity the defects were further subclassified into: A: advanced; M: moderate; and S: slight. In addition, 20 site-, implant-, and patient-related variables were analyzed by generalized estimating equations (GEEs) of multilevel logistic regression models.Results: Based on an a priori power calculation, 332 implants were screened in 47 peri-implantitis patients. Of these, 158 peri-implantitis implants were eligible. The most prevalent defect morphology type was class Ib (55%) followed by class Ia (16.5%), and class IIIb (13.9%). On the contrary, the less frequent defect was class II (1.9%). The most frequent degree of severity was M (50.6%) with S (10.1%) being the least prevalent. Buccal bone loss was significantly greater compared to the other bony walls in class I and class III defects. Age was associated with the type of defect.Age and smoking habit were associated with the morphology of the defects, while smoking habit, type of prosthesis and distance to adjacent implant were associated with the severity of the defects (vertical bone loss).Conclusion: Peri-implantitis defects frequently course with an infraosseous component and often with buccal bone loss. Certain patient-, implant-, and site-specific variables are related with defect morphology and severity. However, morphological patterns for periimplantitis bone defects could not be proven (NCT NCT03777449).K E Y W O R D S alveolar bone, dental implants, diagnostic, implant stability, peri-implantitis, peri-implant mucositis

Background: The present case series assesses the response to reconstructive therapy for the management of 2/3-wall peri-implantitis bone defects following submergedhealing guided bone regeneration. Material and Methods: Fifteen consecutive patients with 27 implants presenting periimplantitis were included. Guided bone regeneration was applied by means of autogenous bone/deproteinized bovine bone mineral grafting mixture and collagen membrane. Patients were assessed at baseline (T0) and at 6 (T1) and 12 months (T2). Clinical and radiographic variables defined the composite success criteria (probing pocket depth [PPD] ≤ 5 mm, no bleeding on probing/suppuration (SUP), no further radiographic bone loss). Patient site-specific comfort was scored using a visual analog scale (VAS). Descriptive statistics was carried out to assess the changes along the study period. Outcomes are reported in terms of mean values (5%-95% percentile values). Results: All the clinical variables substantially changed from T0 through T2. In particular, PPD decreased 3.7 mm (0.7-5.9) from T0 to T2. Likewise, the scores for the modified plaque index (mPI) and modified sulcular bleeding index (mBI) were reduced by 0.5 (−0.5-1.1) and 1.6 (0.4-2.4), respectively. SUP did not display at any implant site at T2 (59.2% implants in 29.2% patients suppurated at T0). Keratinized mucosa decreased 0.6 mm (−0.2-4.4) and while mucosal recession increased 2.5 mm (1.0-4.3). Alike, the radiographic parameters varied significantly from T0 through T2. Infrabony defects were filled by 2.2 mm (0.0-8.6) at T2 and marginal bone loss was reduced by 2.3 mm (−1.1-8.1). The mean VAS score significantly increased from T0 (56.7) through T1 to T2, reaching a score of 96 at T2. At this timepoint, 85.2% of the peri-implantitis lesions were resolved. Conclusions: The proposed surgical approach followed by submerged healing to reconstruct peri-implant bone defects may offer one therapeutic option for failing dental implants. Given the nature of the present study, its effectiveness in comparison to less invasive treatments needs investigation in randomized controlled trials.

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1 Selective phosphodiesterase 4 (PDE4) inhibitors are of potential interest in the treatment of asthma. We examined the eects of the alkaloid S-(+)-glaucine, a PDE4 inhibitor, on human isolated bronchus and granulocyte function. 2 Glaucine selectively inhibited PDE4 from human bronchus and polymorphonuclear leukocytes (PMN) in a non-competitive manner (K i =3.4 mM). Glaucine displaced [ 3 H]-rolipram from its highanity binding sites in rat brain cortex membranes (IC 50 *100 mM). 3 Glaucine inhibited the spontaneous and histamine-induced tone in human isolated bronchus (pD 2 *4.5). Glaucine (10 mM) did not potentiate the isoprenaline-induced relaxation but augmented cyclic AMP accumulation by isoprenaline. The glaucine-induced relaxation was resistant to H-89, a protein kinase A inhibitor. Glaucine depressed the contractile responses to Ca 2+ (pD' 2 *3.62) and reduced the sustained rise of [Ca 2+ ] i produced by histamine in cultured human airway smooth muscle cells (7log IC 50 *4.3). 4 Glaucine augmented cyclic AMP levels in human polymorphonuclear leukocytes challenged with N-formyl-Met-Leu-Phe (FMLP) or isoprenaline, and inhibited FMLP-induced superoxide generation, elastase release, leukotriene B 4 production, [Ca 2+ ] i signal and platelet aggregation as well as opsonized zymosan-, phorbol myristate acetate-, and A23187-induced superoxide release. The inhibitory eect of glaucine on superoxide generation by FMLP was reduced by H-89. 5 In conclusion, Ca 2+ channel antagonism by glaucine appears mainly responsible for the relaxant eect of glaucine in human isolated bronchus while PDE4 inhibition contributes to the inhibitory eects of glaucine in human granulocytes. The very low PDE4/binding site ratio found for glaucine makes this compound attractive for further structure-activity studies.

Background The objective of this trial was to investigate the clinical and radiographic significance of using a mixture of mineralized and demineralized allografts in combination (M) or not (NM) with a resorbable cross‐linked barrier membrane in the reconstructive therapy of peri‐implantitis defects. Methods A two‐arm randomized clinical trial was performed in patients diagnosed with peri‐implantitis that exhibited contained defects. Clinical parameters were recorded at baseline (T0), 6 months (T1), and 12 months (T2). Radiographic parameters were recorded at T0 and T2. A composite criterion for disease resolution was defined a priori. A generalized linear model of repeated measures with generalized estimation equation statistical methods was used. Results Overall, 33 patients (nimplants = 48) completed the study. At T2, mean disease resolution was 77.1%. The use of a barrier membrane did not enhance the probability of disease resolution at T2 (odds ratio [OR] = 1.55, p = 0.737). Conversely, the odds of disease resolution were statistically associated with the modified plaque index recorded at T0 (OR = 0.13, p = 0.006) and keratinized mucosa width (OR = 2.10, p = 0.035). Moreover, women exhibited greater odds to show disease resolution (OR = 5.56, p = 0.02). Conclusion Reconstructive therapy by means of a mixture of mineralized and demineralized allografts is effective in clinically resolving peri‐implantitis and in gaining radiographic marginal bone level. The addition of a barrier membrane to reconstructive therapy of peri‐implantitis does not seem to enhance the outcomes of contained bone defects (NCT05282667).