Contemporary approaches for identifying individual risk for periodontitis.

Key breakthroughs in our understanding of the etiology and principles of predictable treatment of patients with chronic periodontitis first emerged in the late 1960s and carried on into the mid-1980s. Unfortunately, some generalizations of the evidence led many to believe that periodontitis was a predictable result of exposure to bacterial plaque accumulations over time. For a brief period, the initial plaque concept was translated by some to implicate specific bacterial infections, with both concepts (plaque exposure and specific infection) being false assumptions that led to clinical outcomes which were frustrating to both the clinician and the patient. The primary misconceptions were that every individual was equally susceptible to periodontitis, that disease severity was a simple function of magnitude of bacterial exposure over time, and that all patients would respond predictably if treated based on the key principles of bacterial reduction and regular maintenance care. We now know that although bacteria are an essential initiating factor, the clinical severity of periodontitis is a complex multifactorial host response to the microbial challenge. The complexity comes from the permutations of different factors that may interact to alter a single individual's host response to challenge, inflammation resolution and repair, and overall outcome to therapy. Fortunately, although there are many permutations that may influence host response and repair, the pathophysiology of chronic periodontitis is generally limited to mild periodontitis with isolated moderate disease in most individuals. However, approximately 20%-25% of individuals will develop generalized severe periodontitis and probably require more intensive bacterial reduction and different approaches to host modulation of the inflammatory outcomes. This latter group may also have serious systemic implications of their periodontitis. The time appears to be appropriate to use what we know and currently understand to change our approach to clinical care. Our goal would be to increase our likelihood of identifying those patients who have a more biologically disruptive response combined with a more impactful microbial dysbiosis. Current evidence, albeit limited, indicates that for those individuals we should prevent and treat more intensively. This paper discusses what we know and how we might use that information to start individualizing risk and treat some of our patients in a more targeted manner. In my opinion, we are further along than many realize, but we have a great lack of prospective clinical evidence that must be accumulated while we continue to unravel the contributions of specific mechanisms.

Staging and grading of periodontitis: Framework and proposal of a new classification and case definition.

BACKGROUND: Authors were assigned the task to develop case definitions for periodontitis in the context of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The aim of this manuscript is to review evidence and rationale for a revision of the current classification, to provide a framework for case definition that fully implicates state-of-the-art knowledge and can be adapted as new evidence emerges, and to suggest a case definition system that can be implemented in clinical practice, research and epidemiologic surveillance. METHODS: Evidence gathered in four commissioned reviews was analyzed and interpreted with special emphasis to changes with regards to the understanding available prior to the 1999 classification. Authors analyzed case definition systems employed for a variety of chronic diseases and identified key criteria for a classification/case definition of periodontitis. RESULTS: The manuscript discusses the merits of a periodontitis case definition system based on Staging and Grading and proposes a case definition framework. Stage I to IV of periodontitis is defined based on severity (primarily periodontal breakdown with reference to root length and periodontitis-associated tooth loss), complexity of management (pocket depth, infrabony defects, furcation involvement, tooth hypermobility, masticatory dysfunction) and additionally described as extent (localized or generalized). Grade of periodontitis is estimated with direct or indirect evidence of progression rate in three categories: slow, moderate and rapid progression (Grade A-C). Risk factor analysis is used as grade modifier. CONCLUSIONS: The paper describes a simple matrix based on stage and grade to appropriately define periodontitis in an individual patient. The proposed case definition extends beyond description based on severity to include characterization of biological features of the disease and represents a first step towards adoption of precision medicine concepts to the management of periodontitis. It also provides the necessary framework for introduction of biomarkers in diagnosis and prognosis.

A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification.

A classification scheme for periodontal and peri-implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. The workshop was co-sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri-implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri-implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri-implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri-implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table ).

Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.

Quo vadis: what is the future of periodontics? How will we get there?

Approximately 40 years ago periodontists began systematically developing the evidence to treat predictably and prevent gingivitis and periodontitis. More recently, periodontists have been among a small group of skilled dental-implant surgeons leading that revolution in dentistry. Today, much of the mild/localized moderate periodontitis is not treated by periodontists, and an increasing number of implants are placed by dentists with limited surgical training. The current field of periodontics includes a broad range of surgical skills and technologies to regenerate predictably destroyed tissues and manage complex interdisciplinary treatment that may, in some way, involve the tissues that support teeth and implants. In addition, periodontal researchers have shown that moderate-to-severe periodontitis increases the systemic inflammatory burden and transient bacteremias that result in a significant independent role for periodontitis in multiple systemic diseases. Although many periodontists have very advanced practices that incorporate certain aspects of the current and near-future dimensions of periodontics, the innovations and technologies have not yet fully integrated throughout the specialty. It is an appropriate time to ask the question: Quo vadis? Which paths have the potential to deliver great value to our patients and to the health-care system? And who will be our patients in the near future? We propose some key capabilities, knowledge and clinical applications. Perhaps most importantly, we propose new partnerships. Much of the vision centers around the application of special diagnostic technologies and surgical skills to help our dental colleagues better manage complex dental and periodontal cases and to deliver on the promise of reducing systemic inflammation sufficiently to enhance medical management of certain chronic diseases and reduce preterm births. The specialty has always been about retaining teeth in good health and in recent years has focused on controlling oral inflammation to enhance systemic health. We already have several of the key principles, concepts and technologies that are likely to define the role of periodontics in the evolving health-care delivery system. Perhaps it is time to define the mission and start moving toward the future periodontics.

Staging and Grading Discussion of Borderline Cases in Gray Zones.

INTRODUCTION: Staging and grading for chronic periodontal disease, as described in 2018, is designed to focus on key distinctions with the recognition that there is a subset of individuals who are on a different clinical trajectory of disease. The staging and grading framework aids the clinician in generating a periodontal diagnosis, however, some cases fall into gray zones in which the simple diagnostic parameters make it challenging to categorize the patient. These cases do not present with clear clinical findings and medical and dental histories that fit within the simple guidelines defined in the staging and grading tables and subsequent algorithms. CASE PRESENTATION: Two cases are presented and demonstrate typical clinical scenarios that fall into gray zones when it comes to differentiating whether the patient will respond predictably to standard principles of care. Case 1 presents a scenario in which the patient's early history suggests the potential for disease progression and increases the likelihood that the patient may develop a need for complex rehabilitation due to periodontal breakdown. Clinical judgment was used to evaluate whether the patient remained at elevated risk and the potential implications for disease progression. Case 1 was diagnosed with generalized Stage III, Grade B. The initial presentation of Case 2 had a higher severity and complexity and therefore was diagnosed with generalized Stage IV, Grade C. The need for complex rehabilitation in Case 2, however, was not primarily due to periodontitis. CONCLUSION: Decision guidelines and algorithms help in establishing a standardized diagnosis, however cases that fall into gray zones require clinical judgment to establish the most appropriate diagnosis to guide a treatment plan that is personalized based on current knowledge.

Diagnosis of Stage III Periodontitis and Ambiguities of the "Gray Zones" in Between Stage III and Stage IV.

INTRODUCTION: How to best classify the Stage III and IV periodontitis cases that share common features of the most severe clinical attachment loss and the most severe radiographic bone loss? CASE PRESENTATION: Two patients presented features of generalized periodontitis, with severe probing depth and clinical attachment loss that would meet inclusion in both Stage III and IV. The cases retained all teeth but were further complicated by teeth drifting and secondary occlusal trauma. Appropriate disease classification required clinical judgement and led to the final classification of Stage III, Grade C for both cases. CONCLUSION: Patient-based clinical judgement, aiming for long-term preservation of natural dentition, drives the final assignment of staging when the case falls in the "gray zone" that focuses on major differences in Stage III and IV periodontitis.

Challenges and Decision Making for the Classification of Two Complex Periodontal Cases.

FOCUSED CLINICAL QUESTION: What are the fundamental debates and questions related to the newly developed two-vector system for classification of periodontal diseases that have emerged as to how to accurately assign, stage, and grade periodontitis cases? The aim of the present manuscript is to demonstrate the essential thought processes that are needed in utilizing the new periodontitis classification system to diagnose two gray zone cases. SUMMARY: Clinical case 1 includes an 83-year-old male diagnosed with periodontitis and classified as Stage III Generalized Grade B periodontitis, while clinical case 2, a 73-year-old male was classified as presenting Stage IV Generalized Grade B periodontitis. Although clinical and radiographic evaluations revealed similarities between the cases, the thought process that includes clinical judgment is described to guide a more accurate diagnosis following the guidelines of the new classification system. CONCLUSION: The two cases demonstrated here offer an opportunity for clinicians to recognize the essential role of sound clinical judgment in certain cases when applying the new periodontal disease classification system and also clarify questions emerging from implementing this classification system.

Machine learning-assisted immune profiling stratifies peri-implantitis patients with unique microbial colonization and clinical outcomes.

Rationale: The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. Methods: We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling. We utilized a robust outlier-resistant machine learning algorithm for immune deconvolution. Results: Unsupervised clustering identified risk groups with distinct immune profiles, microbial colonization dynamics, and regenerative outcomes. Low-risk patients exhibited elevated M1/M2-like macrophage ratios and lower B-cell infiltration. The low-risk immune profile was characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. Fusobacterium nucleatum and Prevotella intermedia were significantly enriched in high-risk individuals. Although surgery reduced microbial burden at the peri-implant interface in all groups, only low-risk individuals exhibited suppression of keystone pathogen re-colonization. Conclusion: Peri-implant immune microenvironment shapes microbial composition and the course of regeneration. Immune signatures show untapped potential in improving the risk-grading for peri-implantitis.

Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations.

BACKGROUND: A lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs. OBJECTIVE: To determine whether inflammatory genetic markers could stratify patients with knee OA into high and low risk for destructive disease. METHODS: Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen single nucleotide polymorphisms (SNPs) in six inflammatory genes were evaluated for association with radiographic severity and with synovial fluid mediators in a subset of the patients. RESULTS: Interleukin 1 receptor antagonist (IL1RN) SNPs (rs419598, rs315952 and rs9005) predicted Kellgren-Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR=0.15; 95% CI 0.065 to 0.349; p<0.0001), greater joint space width and lower synovial fluid cytokine levels. Carriage of the IL1RN haplotype influenced the age relationship with severity. CONCLUSION: IL1RN polymorphisms reproducibly contribute to disease severity in knee OA and may be useful biomarkers for patient selection in disease-modifying OA drug trials.

Future of preventing and managing common chronic inflammatory diseases.

Chronic inflammation has emerged as a key factor that contributes to some common chronic diseases and reduces lifespan. Studies have identified multiple types of chronic inflammation ranging from autoimmune disease, which attacks specific tissues, to autoinflammatory diseases, which cause low-grade systemic inflammation and contribute to several common chronic diseases. This article highlights new perspectives on the role of chronic inflammation in cardiovascular disease (CVD). Such information is being leveraged to develop new treatment strategies for CVD and may inform how periodontal disease influences CVD.

Clinical application of the new classification of periodontal diseases: Ground rules, clarifications and "gray zones".

BACKGROUND: Successful dissemination of the new classification of periodontitis is facilitated by emphasis on the basic ground rules, clarification of ambiguities, and identification of "gray zones" where thoughtful application of the guidelines by an informed, experienced clinician is paramount to arrive at a correct Stage and Grade. METHODS: Highlighted ground rules are (1) Stage is a patient-based, not a tooth-based concept, therefore, a single Stage is assigned per patient; (2) Stage can shift upward over time, if the periodontal status deteriorates, but the initially assigned Stage is retained even after improvement post-therapy; (3) the complexity factors that determine Stage must be evaluated collectively, not in isolation, to arrive at a clinically meaningful assessment; (4) a single Grade is assigned to a patient based on a deliberate evaluation of the "biological fabric" of the case, in terms of history of/risk for further progression, interplay of risk factors, and the two-way effects of periodontitis or its treatment on general health; (v) shift of Grade over time is possible towards either direction, after thorough, collective, evaluation of changes in the above parameters. Exemplified gray zones include a radiographically intact patient with minimal attachment loss in older age; presence of "frank" periodontitis affecting a single tooth; and assessment of factors that do/do not lead to increased complexity of therapy. CONCLUSION: Differentiating between Stage I/II versus Stage III/IV periodontitis is relatively uncomplicated; further distinction between Stages and correct assignment of Grade requires nuanced, thorough interpretation of a broad array of findings by a knowledgeable clinician.

The American Journal of Cardiology and Journal of Periodontology editors' consensus: periodontitis and atherosclerotic cardiovascular disease.

ACKNOWLEDGMENT: This Editors' Consensus is supported by an educational grant from Colgate-Palmolive, Inc., New York, New York, and is based on a meeting of the authors held in Boston, Massachusetts, on January 9, 2009. DISCLOSURE: Dr. Friedewald has received honoraria for speaking from Novartis, East Hanover, New Jersey. Dr. Kornman is a full-time employee and shareholder of Interleukin Genetics, Waltham, Massachusetts, which owns patents on genetic biomarkers for chronic inflammatory diseases. Dr. Genco is a consultant to Merck, Whitehouse Station, New Jersey. Dr. Ridker has received research support from AstraZeneca, Wilmington, Delaware; Novartis; Pfizer, New York, New York; Roche, Nutley, New Jersey; Sanofi-Aventis, Bridgewater, New Jersey; and Abbott Laboratories, Abbott Park, Illinois. Dr. Ridker has received non-financial research support from Amgen, Thousand Oaks, California. Dr. Ridker is a co-inventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease. Dr. Ridker is a research consultant for Schering-Plough, Kenilworth, New Jersey; Sanofi-Aventis; AstraZeneca; Isis, Carlsbad, California; Novartis; and Vascular Biogenics, Tel Aviv, Israel. Dr. Van Dyke is a co-inventor on patents held by Boston University, Boston, Massachusetts, that relate to inflammation control, including consulting fees. Dr. Roberts has received honoraria for speaking from Merck, Schering-Plough, AstraZeneca, and Novartis. All other individuals in a position to control content disclosed no relevant financial relationships.

Biologically guided implant therapy: A diagnostic and therapeutic strategy of conservation and preservation based on periodontal staging and grading.

Biologically guided implant therapy is based on the new periodontitis classification system recently released by the American Academy of Periodontology and the European Federation of Periodontology that uses staging and grading for the diagnosis of periodontitis. This paper proposes that periodontitis staging and grading should be used in dental implant therapy as a means to ensure maximum conservation of teeth and maximum preservation of alveolar bone. These biologic principles should guide the treatment planning process and supersede a mechanically based, restoratively driven rationale that should be secondary to the biologic principles of conservation and preservation but part of the collaborative treatment planning process. And treatment alternatives throughout the patient's lifetime should be provided for in case of prosthesis loss due to peri-implantitis. The use of grading will help with recognition of systemic aspects that can have a negative impact.

IL1B gene promoter haplotype pairs predict clinical levels of interleukin-1beta and C-reactive protein.

Interleukin-1beta (IL-1beta) activates inflammatory mediator cascades and has been implicated in the pathogenesis of several diseases. Single nucleotide polymorphisms (SNPs) of the IL1B promoter have been associated with various inflammatory diseases. We recently reported that IL1B gene transcription was influenced by four promoter SNPs, and that individual SNP function in vitro was governed by haplotype context. In the present study we tested the in vivo relevance of this observation by comparing IL1B promoter haplotype-pairs with IL-1beta protein levels in 900 gingival tissue fluid samples. Three SNPs (-511, -1464, -3737) defined four IL1B promoter haplotypes that occurred in the study population and could be assigned unambiguously to each chromosome. The four haplotypes defined ten haplotype-pairs of which four pairs, representing 57% of the population, were associated with 28-52% higher IL-1beta protein levels in vivo. Two of these pairs, characterized by homozygosity for the common allele at -3737, were also associated with raised serum levels of C-reactive protein (p = 0.02). We validated these findings in stimulated peripheral blood mononuclear cells (PBMCs) from a separate population (N = 70). PBMCs with IL1B haplotype-pairs associated with higher in vivo levels of IL-1beta produced 86-287% more IL-1beta in vitro than the reference group. We believe that this is the first demonstration of a relationship between in vivo levels of an inflammatory mediator and gene promoter haplotypes on both chromosomes. These findings may apply to other inducible genes and could provide a logical framework for exploring disease risk related to genetic variability in pathogenic mediators.

Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease.

BACKGROUND: Lp(a) lipoprotein binds proinflammatory oxidized phospholipids. We investigated whether levels of oxidized low-density lipoprotein (LDL) measured with use of monoclonal antibody E06 reflect the presence and extent of obstructive coronary artery disease, defined as a stenosis of more than 50 percent of the luminal diameter. METHODS: Levels of oxidized LDL and Lp(a) lipoprotein were measured in a total of 504 patients immediately before coronary angiography. Levels of oxidized LDL are reported as the oxidized phospholipid content per particle of apolipoprotein B-100 (oxidized phospholipid:apo B-100 ratio). RESULTS: Measurements of the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels were skewed toward lower values, and the values for the oxidized phospholipid:apo B-100 ratio correlated strongly with those for Lp(a) lipoprotein (r=0.83, P<0.001). In the entire cohort, the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels showed a strong and graded association with the presence and extent of coronary artery disease (i.e., the number of vessels with a stenosis of more than 50 percent of the luminal diameter) (P<0.001). Among patients 60 years of age or younger, those in the highest quartiles for the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels had odds ratios for coronary artery disease of 3.12 (P<0.001) and 3.64 (P<0.001), respectively, as compared with patients in the lowest quartile. The combined effect of hypercholesterolemia and being in the highest quartiles of the oxidized phospholipid:apo B-100 ratio (odds ratio, 16.8; P<0.001) and Lp(a) lipoprotein levels (odds ratio, 14.2; P<0.001) significantly increased the probability of coronary artery disease among patients 60 years of age or younger. In the entire study group, the association of the oxidized phospholipid:apo B-100 ratio with obstructive coronary artery disease was independent of all clinical and lipid measures except one, Lp(a) lipoprotein. However, among patients 60 years of age or younger, the oxidized phospholipid:apo B-100 ratio remained an independent predictor of coronary artery disease. CONCLUSIONS: Circulating levels of oxidized LDL are strongly associated with angiographically documented coronary artery disease, particularly in patients 60 years of age or younger. These data suggest that the atherogenicity of Lp(a) lipoprotein may be mediated in part by associated proinflammatory oxidized phospholipids.

Mapping the pathogenesis of periodontitis: a new look.

Chronic adult periodontitis is a bacterially induced chronic inflammatory disease that destroys the connective tissue and bone that support teeth. Concepts of the specific mechanisms involved in the disease have evolved with new technologies and knowledge. Histopathologic observations of diseased human tissues were used previously to speculate on the causes of periodontitis and to describe models of pathogenesis. Experimental evidence later emerged to implicate bacterial plaque deposits as the primary factor initiating periodontitis. At the same time, specific bacteria and immunoinflammatory mechanisms were differentially implicated in the disease. In the mid-1990s, early insights about complex diseases, such as periodontitis, led to new conceptual models of the pathogenesis of periodontitis. Those models included the bacterial activation of immunoinflammatory mechanisms, some of which targeted control of the bacterial challenge and others that had adverse effects on bone and connective tissue remodeling. Such models also acknowledged that different environmental and genetic factors modified the clinical phenotype of periodontal disease. However, the models did not capture the dynamic nature of the biochemical processes, i.e., that innate differences among individuals and changes in environmental factors may accelerate biochemical changes or dampen that shift. With emerging genomic, proteomic, and metabolomic data and systems biology tools for interpreting data, it is now possible to begin describing the basic elements of a new model of pathogenesis. Such a model incorporates gene, protein, and metabolite data into dynamic biologic networks that include disease-initiating and -resolving mechanisms. This type of model has a multilevel framework in which the biochemical networks that are regulated by innate and environmental factors can be described and the interrelatedness of networks can be captured. New models in the next few years will be merely frameworks for integrating key knowledge as it becomes available from the "-omics" technologies. However, it is possible to describe some of the key elements of the new models and discuss distinctions between the new and older models. It is hoped that improved conceptual models of pathogenesis will assist in focusing new research and speed the translation of new data into practical applications.

Inflammation and factors that may regulate inflammatory response.

The concept of inflammation has a long history. Although an inflammatory response to injury or another trigger is necessary, chronic diseases, such as coronary heart disease and diabetes, may develop because of unchecked inflammatory responses that have maladapted over decades. For example, the earliest changes in atherosclerosis occur in the endothelium, leading to a cascade of inflammatory responses, such as accumulation of monocytes and T cells, migration of leukocytes into the intima, monocyte differentiation and proliferation, and lesion and fibrous cap development. Inflammatory markers, such as C-reactive protein, may allow clinical insight into these decades-long processes, adding value to predictive measures of disease outcomes. Anti-inflammatory factors, such as adiponectin, may provide further understanding of the inflammatory pathways involved. Greater understanding of the complex pathways involved in inflammation may provide alternative therapeutic strategies to combat inflammation and chronic diseases potentially arising from it.

Staging and grading of periodontitis: Framework and proposal of a new classification and case definition.

BACKGROUND: Authors were assigned the task to develop case definitions for periodontitis in the context of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The aim of this manuscript is to review evidence and rationale for a revision of the current classification, to provide a framework for case definition that fully implicates state-of-the-art knowledge and can be adapted as new evidence emerges, and to suggest a case definition system that can be implemented in clinical practice, research and epidemiologic surveillance. METHODS: Evidence gathered in four commissioned reviews was analyzed and interpreted with special emphasis to changes with regards to the understanding available prior to the 1999 classification. Authors analyzed case definition systems employed for a variety of chronic diseases and identified key criteria for a classification/case definition of periodontitis. RESULTS: The manuscript discusses the merits of a periodontitis case definition system based on Staging and Grading and proposes a case definition framework. Stage I to IV of periodontitis is defined based on severity (primarily periodontal breakdown with reference to root length and periodontitis-associated tooth loss), complexity of management (pocket depth, infrabony defects, furcation involvement, tooth hypermobility, masticatory dysfunction) and additionally described as extent (localized or generalized). Grade of periodontitis is estimated with direct or indirect evidence of progression rate in three categories: slow, moderate and rapid progression (Grade A-C). Risk factor analysis is used as grade modifier. CONCLUSIONS: The paper describes a simple matrix based on stage and grade to appropriately define periodontitis in an individual patient. The proposed case definition extends beyond description based on severity to include characterization of biological features of the disease and represents a first step towards adoption of precision medicine concepts to the management of periodontitis. It also provides the necessary framework for introduction of biomarkers in diagnosis and prognosis.