María José Bendek, María Luisa Mizgier, Carolina Rojas, Valeria Ramírez, Patricia Valdebenito, Anilei Hoare, Marcela Hernández, María José Vasquez, Wilfredo González, Sebastián E Illanes, Alpdogan Kantarci, David Herrera, Lara J Monteiro, Alejandra Chaparro
Background: Epidemiological studies suggest a link between gestational diabetes mellitus (GDM) and periodontitis. In this context, Porphyromonas gingivalis (Pg) and its byproducts, including lipopolysaccharide (Pg-LPS), may translocate to the placenta, potentially intensifying pro-inflammatory mechanisms in a hyperglycemic environment. This study aimed to assess the pro-inflammatory simultaneous stimulus effect of hyperglycemia (HG) and Pg-LPS in human term placental explants.
Methods: Fresh placental explants from healthy (n = 10) and GDM (n = 5) pregnant women were stimulated under normoglycemia (NG), hyperglycemia (HG), Pg-LPS, and a dual stimulus of HG+Pg-LPS. Both placental explants and culture supernatants were assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, immunofluorescence, and multiplex immunoassay to analyze histopathological alterations, Toll-like receptor (TLR)-2, -4, -9 mRNA expression, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation and nuclear immunolocalization, NLRP3 inflammasome expression, and pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α).
Results: The dual stimulus (HG+Pg-LPS) increased fibrinoid necrosis (p < 0.05) and upregulated TLR-4 mRNA (p < 0.05) expression in placental explants, compared to other experimental conditions. NF-κB phosphorylation and nuclear immunolocalization, NLRP3 inflammasome and IL-6, IL-1β, and TNF-α mRNA expression increased upon the dual stimulus in healthy and GDM explants (p < 0.05). Additionally, levels of IL-6 (p < 0.01), IL-1β (p < 0.01), and TNF-α (p < 0.0001) increased in the supernatant from healthy and GDM explants under the dual stimulus. No differences in cytokine levels were observed between healthy and GDM placental explants under the dual stimulus.
Conclusions: A hyperglycemic environment amplifies the pro-inflammatory response to Pg-LPS in human placental explants, suggesting that hyperglycemia synergizes with Pg-LPS in the placenta.
Plain language summary: Bacteria that drive periodontitis, or their products, can enter the bloodstream and reach the placenta. In a high-glucose environment, this exposure can intensify placental inflammation. This study aimed to determine whether exposure to a high-glucose milieu, combined with byproducts of periodontal bacteria, activates inflammatory pathways in the placenta. Our results demonstrate that a high-glucose environment amplifies the inflammatory response to periodontal bacteria in human placentas from both healthy pregnancies and those complicated by gestational diabetes mellitus. These findings advance our understanding of the connection between periodontitis and gestational diabetes mellitus and underscore the role of oral bacterial translocation in placental tissues during pregnancy.
{"title":"Hyperglycemia exacerbates placental inflammation induced by Porphyromonas gingivalis-lipopolysaccharide.","authors":"María José Bendek, María Luisa Mizgier, Carolina Rojas, Valeria Ramírez, Patricia Valdebenito, Anilei Hoare, Marcela Hernández, María José Vasquez, Wilfredo González, Sebastián E Illanes, Alpdogan Kantarci, David Herrera, Lara J Monteiro, Alejandra Chaparro","doi":"10.1002/jper.70051","DOIUrl":"https://doi.org/10.1002/jper.70051","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies suggest a link between gestational diabetes mellitus (GDM) and periodontitis. In this context, Porphyromonas gingivalis (Pg) and its byproducts, including lipopolysaccharide (Pg-LPS), may translocate to the placenta, potentially intensifying pro-inflammatory mechanisms in a hyperglycemic environment. This study aimed to assess the pro-inflammatory simultaneous stimulus effect of hyperglycemia (HG) and Pg-LPS in human term placental explants.</p><p><strong>Methods: </strong>Fresh placental explants from healthy (n = 10) and GDM (n = 5) pregnant women were stimulated under normoglycemia (NG), hyperglycemia (HG), Pg-LPS, and a dual stimulus of HG+Pg-LPS. Both placental explants and culture supernatants were assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, immunofluorescence, and multiplex immunoassay to analyze histopathological alterations, Toll-like receptor (TLR)-2, -4, -9 mRNA expression, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation and nuclear immunolocalization, NLRP3 inflammasome expression, and pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α).</p><p><strong>Results: </strong>The dual stimulus (HG+Pg-LPS) increased fibrinoid necrosis (p < 0.05) and upregulated TLR-4 mRNA (p < 0.05) expression in placental explants, compared to other experimental conditions. NF-κB phosphorylation and nuclear immunolocalization, NLRP3 inflammasome and IL-6, IL-1β, and TNF-α mRNA expression increased upon the dual stimulus in healthy and GDM explants (p < 0.05). Additionally, levels of IL-6 (p < 0.01), IL-1β (p < 0.01), and TNF-α (p < 0.0001) increased in the supernatant from healthy and GDM explants under the dual stimulus. No differences in cytokine levels were observed between healthy and GDM placental explants under the dual stimulus.</p><p><strong>Conclusions: </strong>A hyperglycemic environment amplifies the pro-inflammatory response to Pg-LPS in human placental explants, suggesting that hyperglycemia synergizes with Pg-LPS in the placenta.</p><p><strong>Plain language summary: </strong>Bacteria that drive periodontitis, or their products, can enter the bloodstream and reach the placenta. In a high-glucose environment, this exposure can intensify placental inflammation. This study aimed to determine whether exposure to a high-glucose milieu, combined with byproducts of periodontal bacteria, activates inflammatory pathways in the placenta. Our results demonstrate that a high-glucose environment amplifies the inflammatory response to periodontal bacteria in human placentas from both healthy pregnancies and those complicated by gestational diabetes mellitus. These findings advance our understanding of the connection between periodontitis and gestational diabetes mellitus and underscore the role of oral bacterial translocation in placental tissues during pregnancy.</p>","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Momen A Atieh, Maanas Shah, Abeer Hakam, Omar Al-Karadsheh, Siraj Zabadi, Fawaghi AlAli, Nisheta Sachdev, Andrew Tawse-Smith, Nabeel H M Alsabeeha
<p><strong>Background: </strong>Furcation involvement complicates the management of periodontitis and increases the risk of tooth loss. Conventional methods of detection, such as probing and two-dimensional radiographs, are limited by operator variability and anatomical complexity. Deep learning has shown a potential to detect furcation involvement on radiographic images. The aim of this review was to systematically evaluate the diagnostic potentials of deep learning models in detecting furcation involvement on radiographic images.</p><p><strong>Methods: </strong>Systematic search was conducted in PubMed, EMBASE, CENTRAL, ClinicalTrials.gov and ProQuest for studies published from 2010 to September 2025. Two reviewers independently screened studies, extracted data, and assessed quality using QUADAS-2. Diagnostic metrics (sensitivity, specificity, F1-score, area under the curve (AUC)) were pooled using random-effects meta-analysis. Heterogeneity and publication bias were assessed via I<sup>2</sup> statistics, meta-regression, and funnel plots.</p><p><strong>Results: </strong>Eight studies, including 7814 radiographs of 12,373 molars (periapical, panoramic, cone-beam computed tomography), were analyzed. Deep learning models demonstrated high accuracy: sensitivity 0.93, specificity 0.94, diagnostic odds ratio (DOR) 187, AUC 0.97 with mandibular molars reflecting higher accuracy (sensitivity 0.96, specificity 0.97, DOR 631, AUC 0.99). Fagan plot analysis indicated strong clinical utility. Meta-regression showed no significant effect of dataset type, augmentation, or number of annotators. No publication bias was detected.</p><p><strong>Conclusion: </strong>Deep learning models show promising accuracy in detecting furcation involvement, particularly in mandibular molars, comparable to expert clinicians. Further refinement with larger, diverse datasets is needed to reduce false positives and enable safe clinical integration.</p><p><strong>Plain language summary: </strong>Furcation involvement, a condition where the bone between the roots of a tooth is lost, makes managing gum disease more difficult and increases the risk of tooth loss. Clinical probing remains a reliable and essential method for detecting this condition, while dental X-rays can provide complementary information, particularly in complex cases. This study reviewed the use of deep learning, a type of artificial intelligence (AI), to detect furcation involvement on dental X-rays. Data from eight studies, including more than 7,800 dental radiographs of >12,000 molars, were analyzed and the results showed that deep learning models were highly accurate, performing similarly to expert dentists. Accuracy was slightly higher for lower jaw (mandibular) molars. The study suggests that these AI tools could help dentists detect furcation involvement more reliably. However, more research with larger and more diverse datasets is needed before these tools can be safely used in everyday dental practice.</
{"title":"Diagnostic accuracy of artificial intelligence-based deep learning models in detecting furcation involvement: A systematic review and meta-analysis.","authors":"Momen A Atieh, Maanas Shah, Abeer Hakam, Omar Al-Karadsheh, Siraj Zabadi, Fawaghi AlAli, Nisheta Sachdev, Andrew Tawse-Smith, Nabeel H M Alsabeeha","doi":"10.1002/jper.70055","DOIUrl":"https://doi.org/10.1002/jper.70055","url":null,"abstract":"<p><strong>Background: </strong>Furcation involvement complicates the management of periodontitis and increases the risk of tooth loss. Conventional methods of detection, such as probing and two-dimensional radiographs, are limited by operator variability and anatomical complexity. Deep learning has shown a potential to detect furcation involvement on radiographic images. The aim of this review was to systematically evaluate the diagnostic potentials of deep learning models in detecting furcation involvement on radiographic images.</p><p><strong>Methods: </strong>Systematic search was conducted in PubMed, EMBASE, CENTRAL, ClinicalTrials.gov and ProQuest for studies published from 2010 to September 2025. Two reviewers independently screened studies, extracted data, and assessed quality using QUADAS-2. Diagnostic metrics (sensitivity, specificity, F1-score, area under the curve (AUC)) were pooled using random-effects meta-analysis. Heterogeneity and publication bias were assessed via I<sup>2</sup> statistics, meta-regression, and funnel plots.</p><p><strong>Results: </strong>Eight studies, including 7814 radiographs of 12,373 molars (periapical, panoramic, cone-beam computed tomography), were analyzed. Deep learning models demonstrated high accuracy: sensitivity 0.93, specificity 0.94, diagnostic odds ratio (DOR) 187, AUC 0.97 with mandibular molars reflecting higher accuracy (sensitivity 0.96, specificity 0.97, DOR 631, AUC 0.99). Fagan plot analysis indicated strong clinical utility. Meta-regression showed no significant effect of dataset type, augmentation, or number of annotators. No publication bias was detected.</p><p><strong>Conclusion: </strong>Deep learning models show promising accuracy in detecting furcation involvement, particularly in mandibular molars, comparable to expert clinicians. Further refinement with larger, diverse datasets is needed to reduce false positives and enable safe clinical integration.</p><p><strong>Plain language summary: </strong>Furcation involvement, a condition where the bone between the roots of a tooth is lost, makes managing gum disease more difficult and increases the risk of tooth loss. Clinical probing remains a reliable and essential method for detecting this condition, while dental X-rays can provide complementary information, particularly in complex cases. This study reviewed the use of deep learning, a type of artificial intelligence (AI), to detect furcation involvement on dental X-rays. Data from eight studies, including more than 7,800 dental radiographs of >12,000 molars, were analyzed and the results showed that deep learning models were highly accurate, performing similarly to expert dentists. Accuracy was slightly higher for lower jaw (mandibular) molars. The study suggests that these AI tools could help dentists detect furcation involvement more reliably. However, more research with larger and more diverse datasets is needed before these tools can be safely used in everyday dental practice.</","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anahat Khehra, Joseph Montesano, Lorenzo Tavelli, Chia‐Yu Chen, David M. Kim
Background Conventional bone augmentation for dental implants typically involves particulate grafting materials, with the addition of barrier membranes, to preserve ridge dimensions. This study compares the changes in horizontal ridge width in patients undergoing alveolar ridge preservation (ARP) with a collagenated bovine bone xenograft (BG), with and without a non‐crosslinked collagen membrane (MEM). Methods A 6‐month randomized clinical trial was conducted with 20 participants requiring ARP after tooth extraction. Participants were randomly assigned to two groups: Group 1, which received BG alone, and Group 2, which received BG + MEM. Both groups were allowed to heal by secondary intention. The outcomes of interest included clinical, radiographic, and ultrasonographic changes in hard and soft tissues and histologic and histomorphometric evidence of new bone formation. Results All enrolled participants completed the study, with a mean age of 54.25 ± 17.08 years, including 17 premolars, 1 canine, and 2 incisors. The baseline buccal bone thickness was similar between the groups (group 1: 1.02 ± 0.44 mm; group 2: 0.93 ± 0.45 mm; <jats:italic>p</jats:italic> = 0.662). At 6 months, no significant differences were observed between the groups for keratinized tissue width (group 1: 4.80 ± 1.48 mm; group 2: 4.80 ± 1.14 mm; <jats:italic>p</jats:italic> = 0.999), gingival thickness (group 1: 1.22 ± 0.25 mm; group 2: 1.20 ± 0.35 mm; <jats:italic>p</jats:italic> = 0.650), horizontal bone width at 3 mm from the crest (group 1: 9.02 ± 2.09 mm; group 2: 8.41 ± 1.45 mm; <jats:italic>p</jats:italic> = 0.464), and change in vertical bone at the buccal aspect (group 1: ∆ −0.78 ± 0.59 mm; group 2: ∆ −1.31 ± 1.20 mm; <jats:italic>p</jats:italic> = 0.244). Ultrasound evaluations were consistent with clinical measurements. Histologic analysis showed similar new bone formation between groups (group 1: 25.80% ± 15.48%; group 2: 27.89% ± 18.21%; <jats:italic>p</jats:italic> = 0.803). Conclusion The collagenated bone graft alone yielded comparable outcomes to its combination with a collagen membrane in areas with thick buccal bone, simplifying the treatment process by reducing costs, time, and the need for additional materials. Plain Language Summary This study compared two methods for socket preservation after tooth extraction: one with a bone graft plug alone, and the other with the bone graft plug plus a collagen membrane. Twenty study participants were followed for 6 months after treatment. The hard and soft tissue changes were assessed by clinical, radiographic, ultrasound, and biopsy analyses. Both treatments demonstrated positive results, including stable ridge height and width, new bone formation, and healthy soft tissue healing. The results showed that using only the plug was just as effective as using the plug with the membrane in promoting bone regeneration. This simple approach reduces the need for additional materials, saving time and costs while achieving si
{"title":"Outcomes of alveolar ridge preservation using a collagenated bovine bone xenograft: A randomized controlled trial","authors":"Anahat Khehra, Joseph Montesano, Lorenzo Tavelli, Chia‐Yu Chen, David M. Kim","doi":"10.1002/jper.70036","DOIUrl":"https://doi.org/10.1002/jper.70036","url":null,"abstract":"Background Conventional bone augmentation for dental implants typically involves particulate grafting materials, with the addition of barrier membranes, to preserve ridge dimensions. This study compares the changes in horizontal ridge width in patients undergoing alveolar ridge preservation (ARP) with a collagenated bovine bone xenograft (BG), with and without a non‐crosslinked collagen membrane (MEM). Methods A 6‐month randomized clinical trial was conducted with 20 participants requiring ARP after tooth extraction. Participants were randomly assigned to two groups: Group 1, which received BG alone, and Group 2, which received BG + MEM. Both groups were allowed to heal by secondary intention. The outcomes of interest included clinical, radiographic, and ultrasonographic changes in hard and soft tissues and histologic and histomorphometric evidence of new bone formation. Results All enrolled participants completed the study, with a mean age of 54.25 ± 17.08 years, including 17 premolars, 1 canine, and 2 incisors. The baseline buccal bone thickness was similar between the groups (group 1: 1.02 ± 0.44 mm; group 2: 0.93 ± 0.45 mm; <jats:italic>p</jats:italic> = 0.662). At 6 months, no significant differences were observed between the groups for keratinized tissue width (group 1: 4.80 ± 1.48 mm; group 2: 4.80 ± 1.14 mm; <jats:italic>p</jats:italic> = 0.999), gingival thickness (group 1: 1.22 ± 0.25 mm; group 2: 1.20 ± 0.35 mm; <jats:italic>p</jats:italic> = 0.650), horizontal bone width at 3 mm from the crest (group 1: 9.02 ± 2.09 mm; group 2: 8.41 ± 1.45 mm; <jats:italic>p</jats:italic> = 0.464), and change in vertical bone at the buccal aspect (group 1: ∆ −0.78 ± 0.59 mm; group 2: ∆ −1.31 ± 1.20 mm; <jats:italic>p</jats:italic> = 0.244). Ultrasound evaluations were consistent with clinical measurements. Histologic analysis showed similar new bone formation between groups (group 1: 25.80% ± 15.48%; group 2: 27.89% ± 18.21%; <jats:italic>p</jats:italic> = 0.803). Conclusion The collagenated bone graft alone yielded comparable outcomes to its combination with a collagen membrane in areas with thick buccal bone, simplifying the treatment process by reducing costs, time, and the need for additional materials. Plain Language Summary This study compared two methods for socket preservation after tooth extraction: one with a bone graft plug alone, and the other with the bone graft plug plus a collagen membrane. Twenty study participants were followed for 6 months after treatment. The hard and soft tissue changes were assessed by clinical, radiographic, ultrasound, and biopsy analyses. Both treatments demonstrated positive results, including stable ridge height and width, new bone formation, and healthy soft tissue healing. The results showed that using only the plug was just as effective as using the plug with the membrane in promoting bone regeneration. This simple approach reduces the need for additional materials, saving time and costs while achieving si","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"46 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background This narrative review expands on the concept of inflammation created by metal particles and ions that originate from dental implants and suggests preventative and therapeutic approaches to reduce the problem. Review A review and discussion of various etiologic factors for peri‐implant mucositis and peri‐implantitis are presented, including: foreign body response to embedded residual cement or metal particles or ions, corrosion of the titanium oxide (TiO) layer, tribocorrosion, human and animal histology and studies, treatments, prevention, and maintenance. Conclusions The understanding of etiologic factors for peri‐implant mucositis and peri‐implantitis and their effect on treatment is an evolving science. Biofilm remains a primary etiologic factor. However, a foreign body response from residual cement or metal particles or ions (i.e., metallosis) has been implicated in the onset and progression of peri‐implantitis. While further elucidation of risk factors is appropriate, the treatment adaptations needed to reduce metallosis are simple and easy to apply and should be considered for inclusion in routine diagnosis, therapy, and maintenance. Plain language summary Concepts regarding the etiology and management of inflammatory lesions around dental implants continue to evolve. While bacterial biofilm is widely recognized as the primary etiologic factor, additional contributors such as excess cement and metallic particles acting as foreign bodies have been increasingly emphasized in the literature. These foreign materials act synergistically with biofilm to amplify the inflammatory response. Ions and particles released from implant surfaces can initiate an immunoinflammatory cascade, ultimately resulting in peri‐implant bone loss, a process referred to as metallosis. Unlike the removal of excess cement, which can often be mitigated through judicious cementation techniques or, preferably, the use of screw‐retained restorations, the reduction of metallic particles presents greater clinical challenges. Such particles may originate from biofilm‐induced corrosion, occlusal overload, or even therapeutic interventions aimed at treating peri‐implant inflammation. Minimally invasive strategies have been proposed to address these challenges. Approaches such as the careful use of cotton pellets with sterile saline, and when indicated, the application of minimally invasive flaps under enhanced visualization, have shown promise in reducing the burden of foreign particles. Importantly, stringent oral hygiene measures and consistent maintenance therapy remain indispensable in mitigating these risks and maintaining peri‐implant health.
{"title":"Peri‐implantitis pathogenesis: Novel insights may guide therapeutic interventions","authors":"Thomas G. Wilson","doi":"10.1002/jper.70037","DOIUrl":"https://doi.org/10.1002/jper.70037","url":null,"abstract":"Background This narrative review expands on the concept of inflammation created by metal particles and ions that originate from dental implants and suggests preventative and therapeutic approaches to reduce the problem. Review A review and discussion of various etiologic factors for peri‐implant mucositis and peri‐implantitis are presented, including: foreign body response to embedded residual cement or metal particles or ions, corrosion of the titanium oxide (TiO) layer, tribocorrosion, human and animal histology and studies, treatments, prevention, and maintenance. Conclusions The understanding of etiologic factors for peri‐implant mucositis and peri‐implantitis and their effect on treatment is an evolving science. Biofilm remains a primary etiologic factor. However, a foreign body response from residual cement or metal particles or ions (i.e., metallosis) has been implicated in the onset and progression of peri‐implantitis. While further elucidation of risk factors is appropriate, the treatment adaptations needed to reduce metallosis are simple and easy to apply and should be considered for inclusion in routine diagnosis, therapy, and maintenance. Plain language summary Concepts regarding the etiology and management of inflammatory lesions around dental implants continue to evolve. While bacterial biofilm is widely recognized as the primary etiologic factor, additional contributors such as excess cement and metallic particles acting as foreign bodies have been increasingly emphasized in the literature. These foreign materials act synergistically with biofilm to amplify the inflammatory response. Ions and particles released from implant surfaces can initiate an immunoinflammatory cascade, ultimately resulting in peri‐implant bone loss, a process referred to as metallosis. Unlike the removal of excess cement, which can often be mitigated through judicious cementation techniques or, preferably, the use of screw‐retained restorations, the reduction of metallic particles presents greater clinical challenges. Such particles may originate from biofilm‐induced corrosion, occlusal overload, or even therapeutic interventions aimed at treating peri‐implant inflammation. Minimally invasive strategies have been proposed to address these challenges. Approaches such as the careful use of cotton pellets with sterile saline, and when indicated, the application of minimally invasive flaps under enhanced visualization, have shown promise in reducing the burden of foreign particles. Importantly, stringent oral hygiene measures and consistent maintenance therapy remain indispensable in mitigating these risks and maintaining peri‐implant health.","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"12 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marija Roguljić, Ana Družijanić, Ana Kostović, Ivana Milardović, Lea Starman, Anton Sculean, Ivica Bilić
Background The aim of this study was to explore the association of severe periodontitis (SP) in middle‐aged patients with cognitive dysfunction. Methods Patients with periodontitis were referred to a periodontal examination and underwent neuropsychological testing. We evaluated plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD), gingival recession (GR), clinical attachment level (CAL), dental hard tissues, basic medical history data and oral hygiene habits and oral health‐related quality of life. A neuropsychological assessment was performed using a battery of 6 tests—Five Words Test (WORDS), Trail Making Test A and B (TMT A and B), Digit Span and Reverse (SPAN and REV), Attention Matrices Test (ATT), Symbol Digit Modalities Test (SDMT) to estimate short‐term, long‐term and working memory, visual‐spatial orientation, mental flexibility, and psychomotor speed. Results In total, we included 102 participants, 71 with SP and 31 with mild and moderate periodontitis (MP). Increased age, male sex, lower number of teeth and higher Decayed, Missing and Filled permanent Teeth index (DMFT) were more prevalent among SP than MP group. Logistic regression analysis revealed that lower cognitive performance (lower Symbol Digit Modalities Test score) was associated with greater odds of SP (odds ratio [OR] = 0.77, confidence interval [CI] = 0.64–0.93, p = 0.005) indicating the risk for mild cognitive impairment (MCI). In other words, the odds for MCI among patients with SP were 1.29‐fold compared to those with MP. Conclusion Within the study's limitations, our findings indicate that although MCI was not diagnosed, the risk for MCI was associated with SP in middle‐aged patients. Plain Language Summary This study looked at whether middle‐aged people with severe gum disease (periodontitis) are more likely to have problems with thinking and memory. Researchers worked with 102 patients, some with severe gum disease and others with milder forms. Each participant had their teeth and gums examined and completed tests that measured memory, attention span, and how quickly they could think and react. The results showed that those with more severe gum disease tended to have worse results on a key test, suggesting a link between gum health and brain function. In fact, people with severe gum disease had a higher chance of displaying symptoms of mild cognitive impairment, a condition that can lead to memory loss and dementia over time. These findings suggest that keeping gums healthy may be important not just for oral health, but also for protecting brain health as we age.
{"title":"Increased risk of mild cognitive impairment is associated with severe periodontitis: A cross‐sectional study","authors":"Marija Roguljić, Ana Družijanić, Ana Kostović, Ivana Milardović, Lea Starman, Anton Sculean, Ivica Bilić","doi":"10.1002/jper.70042","DOIUrl":"https://doi.org/10.1002/jper.70042","url":null,"abstract":"Background The aim of this study was to explore the association of severe periodontitis (SP) in middle‐aged patients with cognitive dysfunction. Methods Patients with periodontitis were referred to a periodontal examination and underwent neuropsychological testing. We evaluated plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD), gingival recession (GR), clinical attachment level (CAL), dental hard tissues, basic medical history data and oral hygiene habits and oral health‐related quality of life. A neuropsychological assessment was performed using a battery of 6 tests—Five Words Test (WORDS), Trail Making Test A and B (TMT A and B), Digit Span and Reverse (SPAN and REV), Attention Matrices Test (ATT), Symbol Digit Modalities Test (SDMT) to estimate short‐term, long‐term and working memory, visual‐spatial orientation, mental flexibility, and psychomotor speed. Results In total, we included 102 participants, 71 with SP and 31 with mild and moderate periodontitis (MP). Increased age, male sex, lower number of teeth and higher Decayed, Missing and Filled permanent Teeth index (DMFT) were more prevalent among SP than MP group. Logistic regression analysis revealed that lower cognitive performance (lower Symbol Digit Modalities Test score) was associated with greater odds of SP (odds ratio [OR] = 0.77, confidence interval [CI] = 0.64–0.93, <jats:italic>p</jats:italic> = 0.005) indicating the risk for mild cognitive impairment (MCI). In other words, the odds for MCI among patients with SP were 1.29‐fold compared to those with MP. Conclusion Within the study's limitations, our findings indicate that although MCI was not diagnosed, the risk for MCI was associated with SP in middle‐aged patients. Plain Language Summary This study looked at whether middle‐aged people with severe gum disease (periodontitis) are more likely to have problems with thinking and memory. Researchers worked with 102 patients, some with severe gum disease and others with milder forms. Each participant had their teeth and gums examined and completed tests that measured memory, attention span, and how quickly they could think and react. The results showed that those with more severe gum disease tended to have worse results on a key test, suggesting a link between gum health and brain function. In fact, people with severe gum disease had a higher chance of displaying symptoms of mild cognitive impairment, a condition that can lead to memory loss and dementia over time. These findings suggest that keeping gums healthy may be important not just for oral health, but also for protecting brain health as we age.","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"8 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna G. Barbe, Dalia Beck, Martin Hellmich, Max von Kohout, Sonja H. M. Derman, Dirk Bleiel
Background We examined the clinical effectiveness of shortened outreach periodontal therapy for 3 months in nursing home residents with periodontitis versus controls (no therapy). Methods Nursing home residents with periodontitis were randomly assigned to either (a) one‐time, shortened outreach periodontal therapy adapted to German statutory health guidelines for periodontitis patients in need of care, which included subgingival instrumentation as part of anti‐infective therapy (intervention) or (b) no treatment (control). Changes in bleeding on probing (BOP), plaque index (PI), and pocket probing depth (PPD) were assessed before therapy and at 3 months. Results Thirty‐six participants were included (mean age 85 ± 6 years). In the intervention group, BOP decreased longitudinally from baseline (45 ± 20) to follow‐up (35 ± 16) (change (∆) −10 ± 26; <jats:italic>p</jats:italic> = 0.088; effect size of Cohen's <jats:italic>d</jats:italic> = −0.70 (95% confidence interval (CI) [−1.40 to 0.00]). Significant decreases were observed for PI (from 1.0 ± 0.4 to 0.7 ± 0.4, respectively; ∆−0.3 ± 0.4; <jats:italic>p</jats:italic> = 0.010; Cohen's <jats:italic>d</jats:italic> = −0.56 (95% CI [−1.24 to 0.11]) and PPD (4.5 ± 0.5 to 4.0 ± 0.5 mm; ∆−0.5 ± 0.5; <jats:italic>p</jats:italic> = 0.004; Cohen's <jats:italic>d</jats:italic> = −1.32; 95% CI [−2.05 to −0.59]). Between‐group comparisons revealed significant differences in BOP ( <jats:italic>p</jats:italic> = 0.041) and PPD ( <jats:italic>p</jats:italic> < 0.001), but not PI ( <jats:italic>p</jats:italic> = 0.09). In generalized linear modeling, the treatment group was the main influencing factor, with oral or vestibular plaque localization also affecting treatment outcomes over time. Conclusion In nursing home residents with high plaque levels and periodontal burden, shortened outreach periodontal therapy yielded improvements in periodontal health among nursing home residents, though limited by insufficient oral hygiene and the population's high vulnerability. Trial registration: DRKS database (no. DRKS00029392). CLINICAL TRIAL REGISTRATION German Clinical Trials Register (DRKS), registration number DRKS00029392. Plain language summary This controlled study looked at the effectiveness of a special dental treatment for elderly nursing home residents with gum disease (periodontitis). The treatment, which involved cleaning and instrumentation below the gum line, was compared to no treatment. Thirty‐six participants (aged 85 years, on average) were included in the study. The results showed that after 3 months, the treatment group had a significant reduction in signs of gum inflammation (measured by bleeding on probing) and a decrease in the depth of the pockets around the teeth—both indicators of gum disease. These improvements were not seen in the control group, which did not receive the treatment. The plaque levels in the mouth decreased slightly in the treatment group but did not show a strong difference c
{"title":"Shortened outreach periodontal therapy in nursing home residents with periodontitis: A randomized controlled trial","authors":"Anna G. Barbe, Dalia Beck, Martin Hellmich, Max von Kohout, Sonja H. M. Derman, Dirk Bleiel","doi":"10.1002/jper.70041","DOIUrl":"https://doi.org/10.1002/jper.70041","url":null,"abstract":"Background We examined the clinical effectiveness of shortened outreach periodontal therapy for 3 months in nursing home residents with periodontitis versus controls (no therapy). Methods Nursing home residents with periodontitis were randomly assigned to either (a) one‐time, shortened outreach periodontal therapy adapted to German statutory health guidelines for periodontitis patients in need of care, which included subgingival instrumentation as part of anti‐infective therapy (intervention) or (b) no treatment (control). Changes in bleeding on probing (BOP), plaque index (PI), and pocket probing depth (PPD) were assessed before therapy and at 3 months. Results Thirty‐six participants were included (mean age 85 ± 6 years). In the intervention group, BOP decreased longitudinally from baseline (45 ± 20) to follow‐up (35 ± 16) (change (∆) −10 ± 26; <jats:italic>p</jats:italic> = 0.088; effect size of Cohen's <jats:italic>d</jats:italic> = −0.70 (95% confidence interval (CI) [−1.40 to 0.00]). Significant decreases were observed for PI (from 1.0 ± 0.4 to 0.7 ± 0.4, respectively; ∆−0.3 ± 0.4; <jats:italic>p</jats:italic> = 0.010; Cohen's <jats:italic>d</jats:italic> = −0.56 (95% CI [−1.24 to 0.11]) and PPD (4.5 ± 0.5 to 4.0 ± 0.5 mm; ∆−0.5 ± 0.5; <jats:italic>p</jats:italic> = 0.004; Cohen's <jats:italic>d</jats:italic> = −1.32; 95% CI [−2.05 to −0.59]). Between‐group comparisons revealed significant differences in BOP ( <jats:italic>p</jats:italic> = 0.041) and PPD ( <jats:italic>p</jats:italic> < 0.001), but not PI ( <jats:italic>p</jats:italic> = 0.09). In generalized linear modeling, the treatment group was the main influencing factor, with oral or vestibular plaque localization also affecting treatment outcomes over time. Conclusion In nursing home residents with high plaque levels and periodontal burden, shortened outreach periodontal therapy yielded improvements in periodontal health among nursing home residents, though limited by insufficient oral hygiene and the population's high vulnerability. Trial registration: DRKS database (no. DRKS00029392). CLINICAL TRIAL REGISTRATION German Clinical Trials Register (DRKS), registration number DRKS00029392. Plain language summary This controlled study looked at the effectiveness of a special dental treatment for elderly nursing home residents with gum disease (periodontitis). The treatment, which involved cleaning and instrumentation below the gum line, was compared to no treatment. Thirty‐six participants (aged 85 years, on average) were included in the study. The results showed that after 3 months, the treatment group had a significant reduction in signs of gum inflammation (measured by bleeding on probing) and a decrease in the depth of the pockets around the teeth—both indicators of gum disease. These improvements were not seen in the control group, which did not receive the treatment. The plaque levels in the mouth decreased slightly in the treatment group but did not show a strong difference c","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"20 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad H. A. Saleh, Era Kakar, Giuseppe Troiano, Hamzeh Almashni, Jonathan Misch, Fariba Esperouz, Shahad Alhazmi, Hom‐Lay Wang, Zoltán Baráth, Istvan A. Urban
Background Identifying individuals at high risk for developing peri‐implantitis (PI) and then determining the prognosis for implants with PI is crucial for treatment planning. Methods This study longitudinally followed implants from implant placement retrospectively. The peri‐implant disease risk assessment (IDRA) tool was applied, and the performance of the Kwok and Caton (KC) implant prognostication tool was compared with that of a new tool based on the frequency of progressive bone loss (PBL). The predictive accuracy of IDRA, PBL, and KC was evaluated at the corresponding time points (T1–T5). Fisher's exact test was used to evaluate categorical variables, and the Mann‐Whitney test was used to evaluate continuous variables. Multiple regression models were built to correlate the occurrence of peri‐implantitis and implant survival. The study followed the OHstat and TRIPOD guidelines for reporting. Results 146 dental implants in 87 patients were included (age = 63.19 ± 11.38 years). IDRA classified the implants as 85.62% high‐, 14.38% moderate‐, and 0% low‐risk. The KC scores showed 7.53% of implants with a favorable‐, 65.07% with a questionable‐, and 27.4% with an unfavorable prognosis. IDRA showed limited predictive power with an AUC of 0.533 (95% CI: 0.477–0.590). The KC tool performed much better, where a score of 2 had an AUC of 0.8321 (95% CI: 0.7257–0.9386). PBL yielded a moderate but consistent effectiveness with an AUC of 0.7697 (95% CI: 0.593–0.9463). Conclusion The KC and PBL prognostication tools exhibited good predictive capability for implant survival, while the IDRA tool demonstrated marginal efficacy in predicting the incidence of peri‐implantitis. Plain Language Summary In this study, we followed 87 patients with 146 implants over time to test how well different tools can predict implant health and survival. We tested three tools, IDRA for predicting peri‐implantitis, the KC system, and a new tool based on progressive bone loss for predicting implant survival. After 2 years with the implant crowns in place, we checked for cases of peri‐implantitis. At the final follow‐up (up to 8 years), the implant survival was assessed. We found that IDRA was not effective in predicting which implants developed peri‐implantitis, even in high‐ and moderate‐risk implants. In contrast, the KC tool was much more accurate, predicting implant survival in about 80% of cases. The PBL tool was also good in predicting implant survival, but slightly less accurate than the KC tool.
{"title":"Predicting peri‐implantitis incidence and implant failure via risk‐assessment and prognostication tools: A validation study","authors":"Muhammad H. A. Saleh, Era Kakar, Giuseppe Troiano, Hamzeh Almashni, Jonathan Misch, Fariba Esperouz, Shahad Alhazmi, Hom‐Lay Wang, Zoltán Baráth, Istvan A. Urban","doi":"10.1002/jper.70047","DOIUrl":"https://doi.org/10.1002/jper.70047","url":null,"abstract":"Background Identifying individuals at high risk for developing peri‐implantitis (PI) and then determining the prognosis for implants with PI is crucial for treatment planning. Methods This study longitudinally followed implants from implant placement retrospectively. The peri‐implant disease risk assessment (IDRA) tool was applied, and the performance of the Kwok and Caton (KC) implant prognostication tool was compared with that of a new tool based on the frequency of progressive bone loss (PBL). The predictive accuracy of IDRA, PBL, and KC was evaluated at the corresponding time points (T1–T5). Fisher's exact test was used to evaluate categorical variables, and the Mann‐Whitney test was used to evaluate continuous variables. Multiple regression models were built to correlate the occurrence of peri‐implantitis and implant survival. The study followed the OHstat and TRIPOD guidelines for reporting. Results 146 dental implants in 87 patients were included (age = 63.19 ± 11.38 years). IDRA classified the implants as 85.62% high‐, 14.38% moderate‐, and 0% low‐risk. The KC scores showed 7.53% of implants with a favorable‐, 65.07% with a questionable‐, and 27.4% with an unfavorable prognosis. IDRA showed limited predictive power with an AUC of 0.533 (95% CI: 0.477–0.590). The KC tool performed much better, where a score of 2 had an AUC of 0.8321 (95% CI: 0.7257–0.9386). PBL yielded a moderate but consistent effectiveness with an AUC of 0.7697 (95% CI: 0.593–0.9463). Conclusion The KC and PBL prognostication tools exhibited good predictive capability for implant survival, while the IDRA tool demonstrated marginal efficacy in predicting the incidence of peri‐implantitis. Plain Language Summary In this study, we followed 87 patients with 146 implants over time to test how well different tools can predict implant health and survival. We tested three tools, IDRA for predicting peri‐implantitis, the KC system, and a new tool based on progressive bone loss for predicting implant survival. After 2 years with the implant crowns in place, we checked for cases of peri‐implantitis. At the final follow‐up (up to 8 years), the implant survival was assessed. We found that IDRA was not effective in predicting which implants developed peri‐implantitis, even in high‐ and moderate‐risk implants. In contrast, the KC tool was much more accurate, predicting implant survival in about 80% of cases. The PBL tool was also good in predicting implant survival, but slightly less accurate than the KC tool.","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"29 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Historically, immunological memory was considered an exclusive feature of adaptive immunity. However, innate immune cells have recently been shown to record and maintain epigenetically imprinted memory of earlier infectious or inflammatory challenges. In the bone marrow, hematopoietic stem and progenitor cells (HSPCs) can also build inflammatory memory, which leads to trained myelopoiesis, that is, the production of high numbers of myeloid cells with increased inflammatory responsiveness to future challenges. Another condition affecting HSPCs and causing overproduction of leukocytes with increased inflammatory responsiveness is clonal hematopoiesis of indeterminate potential (CHIP). Occurring at high prevalence in the elderly, CHIP is driven predominantly by somatic mutations in genes encoding epigenetic modifiers, hence altering the epigenetic landscape of hematopoietic progenitors and their mature progeny. Although trained myelopoiesis and CHIP may have beneficial effects, they can also act in a maladaptive context and aggravate inflammation in periodontal disease and systemic conditions, thereby forming a common mechanistic basis for inflammatory comorbidities. This review discusses recent experimental and clinical evidence on the mechanisms and implications of maladaptive hematopoiesis—due to trained myelopoiesis or CHIP—‐in periodontitis and associated inflammatory comorbidities. Plain language summary Traditionally, immune memory—the ability to “remember” past infections—was thought to be limited to the adaptive immune system. But recent discoveries show that even the more ancient part of the immune system, the innate immune system, can also develop a form of memory. This memory is stored through changes in how genes are regulated, and it begins in the bone marrow. There, blood‐forming stem cells can be “trained” by previous infection or inflammation to produce more immune cells that respond more aggressively to future threats, a process known as trained myelopoiesis. An analogous process happens in a condition called clonal hematopoiesis of indeterminate potential (CHIP), which is common in older adults. In CHIP, mutations in certain genes cause the bone marrow to overproduce immune cells that are overly reactive. While trained myelopoiesis and CHIP may exert protective effects, they can also backfire. Both trained myelopoiesis and CHIP have been linked to increased inflammation in gum disease and associated systemic conditions. This review explores how bone marrow–driven changes in the production and activity of immune cells may contribute to a shared underlying cause of multiple inflammatory disorders and why understanding these processes could open new doors for treatment and prevention.
{"title":"Epigenetic inflammatory memory and periodontal disease: Mechanisms and clinical significance for comorbidities","authors":"George Hajishengallis","doi":"10.1002/jper.70040","DOIUrl":"https://doi.org/10.1002/jper.70040","url":null,"abstract":"<jats:label/> Historically, immunological memory was considered an exclusive feature of adaptive immunity. However, innate immune cells have recently been shown to record and maintain epigenetically imprinted memory of earlier infectious or inflammatory challenges. In the bone marrow, hematopoietic stem and progenitor cells (HSPCs) can also build inflammatory memory, which leads to trained myelopoiesis, that is, the production of high numbers of myeloid cells with increased inflammatory responsiveness to future challenges. Another condition affecting HSPCs and causing overproduction of leukocytes with increased inflammatory responsiveness is clonal hematopoiesis of indeterminate potential (CHIP). Occurring at high prevalence in the elderly, CHIP is driven predominantly by somatic mutations in genes encoding epigenetic modifiers, hence altering the epigenetic landscape of hematopoietic progenitors and their mature progeny. Although trained myelopoiesis and CHIP may have beneficial effects, they can also act in a maladaptive context and aggravate inflammation in periodontal disease and systemic conditions, thereby forming a common mechanistic basis for inflammatory comorbidities. This review discusses recent experimental and clinical evidence on the mechanisms and implications of maladaptive hematopoiesis—due to trained myelopoiesis or CHIP—‐in periodontitis and associated inflammatory comorbidities. Plain language summary Traditionally, immune memory—the ability to “remember” past infections—was thought to be limited to the adaptive immune system. But recent discoveries show that even the more ancient part of the immune system, the innate immune system, can also develop a form of memory. This memory is stored through changes in how genes are regulated, and it begins in the bone marrow. There, blood‐forming stem cells can be “trained” by previous infection or inflammation to produce more immune cells that respond more aggressively to future threats, a process known as trained myelopoiesis. An analogous process happens in a condition called clonal hematopoiesis of indeterminate potential (CHIP), which is common in older adults. In CHIP, mutations in certain genes cause the bone marrow to overproduce immune cells that are overly reactive. While trained myelopoiesis and CHIP may exert protective effects, they can also backfire. Both trained myelopoiesis and CHIP have been linked to increased inflammation in gum disease and associated systemic conditions. This review explores how bone marrow–driven changes in the production and activity of immune cells may contribute to a shared underlying cause of multiple inflammatory disorders and why understanding these processes could open new doors for treatment and prevention.","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"172 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Flavia Teles, Ganesh Chandrasekaran, Lynn Martin, Poojan Shrestha, Kevin Moss, Michele Patel, Michael J. Kallan, Camila Furquim, Andrew J. Cucchiara, James D. Beck, Kari E. North, Joseph Glessner, Kimon Divaris
Background To add to the knowledge base of periodontal genomics, we carried out a genome‐wide association study (GWAS) of periodontitis severity and progression among 416 mixed‐ethnicity adult participants of a periodontitis clinical study. Methods Participants were 168 adults (mean age = 50 years, 46% males) with severe periodontitis and 248 adults (mean age = 48 years, 40% males) without severe periodontitis, including 147 with mild periodontitis and 101 periodontally healthy. Disease progression information over a 12‐month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry using a conventional <jats:italic>p </jats:italic> < 5x10 <jats:sup>−8</jats:sup> genome‐wide statistical significance criterion. Genome‐wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic/Latinos, 4,554 European Americans, and 973 African Americans. Results All GWAS single nucleotide polymorphisms (SNPs) explained 34% of phenotypic variance between periodontitis cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome‐wide significant loci associated with disease progression ( <jats:italic>SUMO2P2</jats:italic> , small ubiquitin‐like modifier 2, rs72691774, <jats:italic>p</jats:italic> = 1.9x10 <jats:sup>−8</jats:sup> ] and <jats:italic>CUBN</jats:italic> (cubilin, rs565051161, <jats:italic>p</jats:italic> = 3.9x10 <jats:sup>−8</jats:sup> ). <jats:italic>CUBN</jats:italic> was strongly associated with periodontal disease in the independent samples of African Americans (rs7082270, <jats:italic>p </jats:italic> = 3.1x10 <jats:sup>−7</jats:sup> ) and Hispanic/Latinos (rs1276710, <jats:italic>p</jats:italic> = 1.5x10 <jats:sup>−5</jats:sup> ), albeit the lead SNPs were rare and differed in each population. Meanwhile, <jats:italic>ZBTB16</jats:italic> (zinc finger and BTB domain‐containing 16) showed the strongest evidence of association with severe periodontitis (rs454802, <jats:italic>p </jats:italic> = 2.2x10 <jats:sup>−7</jats:sup> ). Conclusions This study's results emanate from a well‐characterized cohort of periodontitis severity and progression and add to the knowledge base of periodontal genomics and the underlying individual disease susceptibility. Plain language summary This study assessed the association of gene variants in association with gum disease severity and progression in 416 participants of a clinical study. Participants were 168 adults (mean age = 50 years, 46% males) with severe disease and 248 adults (mean age = 48 years, 40% males) without severe disease, including 147 with mild disease and 101 without disease. Disease progression information over a 12‐month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for ag
背景：为了增加牙周基因组学的知识基础，我们在一项牙周炎临床研究的416名混合种族成年参与者中进行了牙周炎严重程度和进展的全基因组关联研究（GWAS）。方法168例重度牙周炎成人（平均年龄50岁，男性46%）和248例非重度牙周炎成人（平均年龄48岁，男性40%），其中147例为轻度牙周炎，101例牙周健康。其中368名参与者12个月的疾病进展信息可用。单标记发现分析依赖于使用传统的p <； 5 × 10−8全基因组统计显著性标准调整的年龄、性别和遗传决定祖先的逻辑回归模型。在10019名西班牙裔/拉丁裔、4554名欧洲裔美国人和973名非洲裔美国人的外部队列中，对全基因组范围内的重要基因座进行了注释和检查，以确定其与牙周病特征的关联。结果所有GWAS单核苷酸多态性（snp）解释了牙周炎病例和对照组之间34%的表型差异和57%的疾病进展差异。我们发现了2个与疾病进展相关的全基因组显著位点（SUMO2P2，小泛素样修饰子2，rs72691774, p = 1.9x10−8）和CUBN （cubilin, rss565051161, p = 3.9x10−8）。在非裔美国人（rs7082270, p = 3.1x10−7）和西班牙裔/拉丁裔（rs1276710, p = 1.5x10−5）的独立样本中，CUBN与牙周病密切相关，尽管在每个人群中，领头snp罕见且不同。同时，ZBTB16（锌指和含BTB结构域16）与严重牙周炎的相关性最强（rs454802, p = 2.2x10−7）。结论：本研究的结果来自一个具有良好特征的牙周炎严重程度和进展队列，并增加了牙周基因组学和潜在个体疾病易感性的知识库。这项研究评估了416名临床研究参与者中与牙龈疾病严重程度和进展相关的基因变异的关系。参与者为168名重症成人（平均年龄50岁，男性46%）和248名非重症成人（平均年龄48岁，男性40%），其中147名轻症患者和101名无疾病患者。其中368名参与者12个月的疾病进展信息可用。单标记发现分析依赖于年龄、性别和遗传决定血统调整后的逻辑回归模型。在10019名西班牙裔/拉丁裔、4554名欧洲裔美国人和973名非洲裔美国人的外部队列中，对全基因组范围内的重要基因座进行了注释和检查，以确定其与牙周病特征的关联。在这项研究中，所有基因变异解释了34%的病例和对照组之间的差异以及57%的疾病进展差异。我们确定了2个与疾病进展相关的全基因组显著位点（SUMO2P2和CUBN）。在非裔美国人和西班牙裔/拉丁裔的独立样本中，CUBN与牙周病密切相关。ZBTB16与严重牙周炎的相关性最强。这项研究的结果来自于一个具有良好特征的牙周炎严重程度和进展队列，表明大约三分之一的疾病严重程度差异和超过一半的疾病进展差异可归因于个体易感性，并增加了牙周基因组学的知识库。
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Hatice Hasturk, Daniel Boyd, Kathleen MacDonald‐Parsons, Stephanie Turner‐Cahill, Joon Seong, Nicola West, Heather J. Doucette
Background This first‐in‐human clinical study aimed to evaluate the safety and efficacy of a bioglass incorporated in a toothpaste, in reducing dentin hypersensitivity (DH) compared to a sodium fluoride (NaF) toothpaste over a 2‐week period. Methods A double‐blind, randomized, parallel‐arm, proof‐of‐concept clinical trial was conducted with 46 participants experiencing self‐reported and clinically confirmed DH. Participants were assigned to 1 of 2 groups: (1) Test toothpaste (5 wt% bioglass with 1425 ppm fluoride as NaF), or (2) NaF toothpaste (1425 ppm fluoride). Outcomes included Schiff Airblast Sensitivity Score (primary endpoint), Visual Analog Scale (VAS) for pain, and Yeaple Probe tactile sensitivity (secondary endpoints). Statistical analyses, including analysis of covariance (ANCOVA) and descriptive statistics, were performed to evaluate intergroup differences. Results The Test group exhibited a statistically significant reduction in Schiff Airblast Sensitivity Scores at Day 14 compared to the NaF group (ΔMean: −0.8 vs. −0.5, p = 0.0341). Significant improvements were also observed in VAS pain scores in as little as 2 days (ΔMean: −1.03 vs. 0.04, p = 0.0057). Rapid pain relief was noted within 2 days, indicating both immediate and cumulative effects. The difference in tactile scores was not statistically significant between groups although greater change was seen with Test toothpaste (ΔMean 13 vs. 3 g; p = 0.068). No severe adverse events were reported, and safety profiles were comparable across groups. Conclusion The toothpaste containing the bioglass demonstrated superior efficacy in alleviating DH symptoms at both early and later time points through its mechanism of rapid tubule occlusion. This innovative approach aligns with World Health Organization (WHO) recommendations for fluoride use and addresses unmet needs in DH management globally. Further research is warranted to explore its long‐term applications in preventive and restorative dentistry. Clinical trials registration U.S. National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ) ID NCT06166745.
本研究是首个人体临床研究，旨在评估牙膏中加入生物玻璃与氟化钠（NaF）牙膏相比，在2周内降低牙本质过敏（DH）的安全性和有效性。方法采用双盲、随机、平行组、概念验证的临床试验，纳入46名自我报告和临床确诊的DH患者。参与者被分配到两组中的一组：(1)测试牙膏（5 wt%生物玻璃，含1425 ppm氟作为NaF），或(2)NaF牙膏（1425 ppm氟）。结果包括希夫空气爆炸敏感性评分（主要终点）、疼痛视觉模拟量表（VAS）和耶普尔探针触觉敏感性（次要终点）。统计分析包括协方差分析（ANCOVA）和描述性统计来评估组间差异。结果与NaF组相比，试验组在第14天的希夫空气爆炸敏感性评分有统计学意义的降低（ΔMean: - 0.8 vs. - 0.5, p = 0.0341）。VAS疼痛评分在短短2天内也有显著改善（ΔMean: - 1.03 vs. 0.04, p = 0.0057）。2天内疼痛迅速缓解，显示了即时和累积效应。两组之间的触觉评分差异无统计学意义，但牙膏测试的变化更大（ΔMean 13 vs. 3 g; p = 0.068）。未报告严重不良事件，各组间的安全性具有可比性。结论含生物玻璃牙膏通过其快速封堵小管的机制，在早期和后期时间点均表现出较好的缓解DH症状的效果。这一创新方法与世界卫生组织（世卫组织）关于氟化物使用的建议一致，并解决了全球卫生管理中未满足的需求。进一步研究其在牙科预防和修复中的长期应用是有必要的。临床试验注册美国国立卫生研究院临床试验注册中心（http://www.clinicaltrials.gov）编号NCT06166745。
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