Reconstructive Approach in Residual Periodontal Pockets with Biofunctionalized Heterografts-A Retrospective Comparison of 12-Month Data from Three Centers.

The regenerative capacity of well-preserved blood clots may be enhanced by biologics like enamel matrix derivative (EMD). This retrospective analysis compares outcomes reported by three centers using different heterografts. Center 1 (C1) treated intrabony defects combining cross-linked high-molecular-weight hyaluronic acid (xHyA) with a xenograft; center 2 (C2) used EMD with an allograft combination to graft a residual pocket. Center 3 (C3) combined xHyA with the placement of a resorbable polymer membrane for defect cover. Clinical parameters, BoP reduction, and radiographically observed defect fill at 12-month examination are reported. The 12-month evaluation yielded significant improvements in PPD and CAL at each center (p < 0.001, respectively). Analyses of Covariance revealed significant improvements in all parameters, and a significantly greater CAL gain was revealed for C2 vs. C1 (p = 0.006). Radiographic defect fill presented significantly higher scores for C2 and C3 vs. C1 (p = 0.003 and = 0.014; C2 vs. C3 p = 1.00). Gingival recession increased in C1 and C3 (p = 1.00), while C2 reported no GR after 12 months (C2:C1 p = 0.002; C2:C3 p = 0.005). BoP tendency and pocket closure rate shared similar rates. Within the limitations of the study, a data comparison indicated that xHyA showed a similar capacity to enhance the regenerative response, as known for EMD. Radiographic follow-up underlined xHyA's unique role in new attachment formation.

Prenyltransferase gene expression reveals an essential role of prenylation for the inflammatory response in human gingival fibroblasts.

BACKGROUND: Prenyltrasferases (PTases) are a class of enzymes known to be responsible for promoting posttranslational modification at the carboxyl terminus of proteins containing a so-called CaaX-motif. The process is responsible for proper membrane localization and the appropriate function of several intracellular signaling proteins. Current research demonstrating the pathomechanistic importance of prenylation in inflammatory illnesses emphasizes the requirement to ascertain the differential expression of PT genes under inflammatory settings, particularly in periodontal disease. METHODS: Telomerase-immortalized human gingival fibroblasts (HGF-hTert) were cultured and treated with either inhibitors of prenylation (PTI) lonafarnib, tipifarnib, zoledronic acid, or atorvastatin at concentrations of 10 µM in combination with or without 10 µg Porphyromonas gingivalis lipopolysaccharide (LPS) for 24 h. Prenyltransferase genes FNTB, FNTA, PGGT1B, RABGGTA, RABGGTB, and PTAR1 as well as inflammatory marker genes MMP1 and IL1B were detected using quantitative real-time polymerase chain reaction (RT-qPCR). Immunoblot and protein immunoassay were used to confirm the results on the protein level. RESULTS: RT-qPCR experiments revealed significant upregulation of IL1B, MMP1, FNTA, and PGGT1B upon LPS treatment. PTase inhibitors caused significant downregulation of the inflammatory cytokine expression. Interestingly, FNTB expression was significantly upregulated in response to any PTase inhibitor in combination with LPS, but not upon LPS treatment only, indicating a vital role of protein farnesyltransferase in the proinflammatory signaling cascade. CONCLUSIONS: In this study, distinct PTase gene expression patterns in pro-inflammatory signaling were discovered. Moreover, PTase inhibiting drugs ameliorated inflammatory mediator expression by a significant margin, indicating that prenylation is a major pre-requisite for innate immunity in periodontal cells.

Microcirculation and neutrophil-related cytokine concentrations are not altered around narrow diameter implants in T2DM patients during wound healing.

OBJECTIVES: The aim of this study was to assess the microcirculation and the expression patterns of wound-healing-related cytokines around narrow-diameter implants in type 2 diabetes mellitus (T2DM) and normo-glycemic patients. MATERIALS AND METHODS: A total of 31 patients, 16 of which diagnosed with T2DM (HbA1c > 6.5) and 15 normo-glycemic patients, received narrow diameter implants in the posterior mandible or maxilla. During the 3-month healing period, soft-tissue perfusion was monitored via laser Doppler flowmetry. Peri-implant fluid (PICF) was harvested and analyzed for concentrations of interleukin-1ß (IL-1ß), interleukin-23 (IL-23), interleukin-17 (IL-17), and granulocyte colony-stimulating factor (G-CSF) by a multiplex, bead-based immunoassay. RESULTS: Microcirculatory perfusion patterns during wound healing exhibited no significant differences throughout the observation period. IL-1ß concentrations were expectedly elevated during the early phases of wound healing. At the first visit after surgery, IL-23 concentrations were significantly higher in implants of diabetic patients. This difference was diminished over the course of the observation period. For the other tested analytes, no differences were observable between both groups. CONCLUSION: Wound healing after implant surgery was similar in T2DM and healthy patients. Hydrophilic-surface titanium-zirconium implants with reduced diameter may be considered for implant therapy of diabetes mellitus type II patients. REGISTRATION NUMBER: NCT04630691 (clinicaltrials.gov).

Analyzing the postulated inhibitory effect of Manumycin A on farnesyltransferase.

Manumycin A is postulated to be a specific inhibitor against the farnesyltransferase (FTase) since this effect has been shown in 1993 for yeast FTase. Since then, plenty of studies investigated Manumycin A in human cells as well as in model organisms like Caenorhabditis elegans. Some studies pointed to additional targets and pathways involved in Manumycin A effects like apoptosis. Therefore, these studies created doubt whether the main mechanism of action of Manumycin A is FTase inhibition. For some of these alternative targets half maximal inhibitory concentrations (IC50) of Manumycin A are available, but not for human and C. elegans FTase. So, we aimed to 1) characterize missing C. elegans FTase kinetics, 2) elucidate the IC50 and Ki values of Manumycin A on purified human and C. elegans FTase 3) investigate Manumycin A dependent expression of FTase and apoptosis genes in C. elegans. C. elegans FTase has its temperature optimum at 40°C with KM of 1.3 µM (farnesylpyrophosphate) and 1.7 µM (protein derivate). Whilst other targets are inhibitable by Manumycin A at the nanomolar level, we found that Manumycin A inhibits cell-free FTase in micromolar concentrations (Ki human 4.15 µM; Ki C. elegans 3.16 µM). Furthermore, our gene expression results correlate with other studies indicating that thioredoxin reductase 1 is the main target of Manumycin A. According to our results, the ability of Manumycin A to inhibit the FTase at the micromolar level is rather neglectable for its cellular effects, so we postulate that the classification as a specific FTase inhibitor is no longer valid.

Adjunctive Application of Hyaluronic Acid in Combination with a Sodium Hypochlorite Gel for Non-Surgical Treatment of Residual Pockets Reduces the Need for Periodontal Surgery-Retrospective Analysis of a Clinical Case Series.

The comprehensive treatment of periodontitis stage 2 to 4 aims at the resolution of periodontal inflammation and "pocket closure", which implies a residual probing depth of ≤4 mm and a negative BoP. However, supportive periodontal therapy (SPT) regularly leaves behind persistent periodontal pockets with 5 or more mm in residual PPD and sites that often re-colonize and re-infect. Various adjunctive options for subgingival instrumentation have been proposed to enhance the antimicrobial effects to better control the re-infection of these residual sites. The locally applied adjuncts, based on their anti-inflammatory effect, are sodium hypochlorite antiseptic cleaning gel and cross-linked hyaluronic acid (xHyA). Both recently moved into the focus of clinical research on non-surgical and surgical therapy for periodontitis. The surgical use of xHyA indicates regenerative potential, supporting periodontal regeneration. This case series retrospectively analyzes the clinical benefits of the consecutive flapless application of sodium-hypochlorite-based cleaning gel and xHyA at the SPT to achieve pocket closure, thereby reducing the need for periodontal surgery. In 29 patients, 111 sites received the treatment sequence. At 6-month re-evaluation, an overall PPD reduction exceeding 2 mm was achieved, associated with a similar CAL gain (2.02 mm); the bleeding tendency (BoP) was reduced by >60%. Pocket closure occurred in almost 25% of all the sites. Within their limits, the present data suggest that the proposed combined adjunctive treatment of residual active periodontal sites yielded significant improvement in the clinical parameters. Further studies in RCT format are required to confirm these observations.

Implant stability of narrow diameter implants in hyperglycemic patients-A 3-month case-control study.

OBJECTIVES: The aim of this prospective case-control study was to compare the development of implant stability quotients of narrow diameter implants in patients with type 2 diabetes mellitus (T2DM) and healthy individuals within the first 3 months after implant insertion. METHODS: Sixteen patients with T2DM (HbA1C > 6.5%) as test group and 16 nondiabetic patients (HbA1C < 5.9%) as the control group were evaluated. All patients received narrow-diameter tissue level implants in an edentulous area posterior to the canine. The implant stability was measured by means of resonance frequency analysis after 3 days, 7 days, 4 weeks, and 3 months postplacement. Statistical analysis of intergroup differences and correlation to HbA1c values and treated jaw was performed in PRISM 8. RESULTS: The means for implant stability quotients showed a significant increase between Day 3 and 3-month assessment in both groups. No significant differences between study groups and no correlation of implant stability to HbA1c were found. CONCLUSION: The present study shows encouraging clinical outcomes for narrow-diameter implants inserted in the posterior zone in patients with uncontrolled T2DM.

Evidence-based selection of reference genes for RT-qPCR assays in periodontal research.

OBJECTIVE: To underline the necessity of adequate reference genes for real-time quantitative polymerase chain reaction (RT-qPCR) and evaluate a novel tool for condition-specific reference gene selection. BACKGROUND: RT-qPCR is a commonly used experimental technique that allows for highly sensitive analysis of gene transcription. Moreover, the use of internal reference genes as a means for relative quantification has rendered RT-qPCR a straightforward method for a variety of sciences, including dentistry. However, the expressional stability of internal reference genes must be evaluated for every assay in order to account for possible quantification bias. MATERIALS AND METHODS: Herein, we used the software tool RefGenes to identify putatively stable reference genes with the help of microarray datasets and evaluated them. Additionally, we propose an evidence-based workflow for adequate normalization of thusly identified genes. Human gingival fibroblasts (HGF-hTert), human acute leukemia-derived monocytes (THP-1), and telomerase immortalized gingival keratinocytes (TIGKs) were subjected to set-ups simulating various glycemic conditions and lipopolysaccharide challenges. Five common housekeeping genes (HKGs) and five genes from RefGenes were selected as targets and RT-qPCR was performed subsequently. Then, normalization algorithms Bestkeeper, Normfinder, and geNorm were used for further analysis of the putative reference gene stability. RESULTS: RefGenes-derived targets exhibited the highest stability values in THP-1 and TIGK cell lines. Moreover, unacceptable standard variations were observed for some common HKG like ß-actin. However, common HKG exhibited good stability values in HGF-hTert cells. CONCLUSION: The results indicate that microarray-based preselection of putative reference genes is a valuable refinement for RT-qPCR studies. Accordingly, the present study proposes a straightforward workflow for evidence-based preselection and validation of internal reference genes.

Biomechanical Stability of Primary and Revision Sacroiliac Joint Fusion Devices: A Cadaveric Study.

STUDY DESIGN: An in vitro biomechanics study. OBJECTIVE: To evaluate the efficacy of triangular titanium implants in providing mechanical stabilization to a sacroiliac joint with primary and revision sized implants. METHODS: Ten lumbopelvic cadaveric specimens were tested in 4 stages: intact, pubic symphysis sectioned, primary, and simulated revision. Primary treatment was performed using 3 laterally placed triangular titanium implants. To simulate revision conditions before and after bone ingrowth and ongrowth on the implants, 7.5-mm and 10.75-mm implants were randomly assigned to one side of each specimen during the simulated revision stage. A 6 degrees of freedom spinal loading frame was used to load specimens in 4 directions: flexion extension, lateral bending, axial torsion, and axial compression. Biomechanical evaluation was based on measures of sacroiliac joint rotational and translational motion. RESULTS: Both primary and revision implants showed the ability to reduce translational motion to a level significantly lower than the intact condition when loaded in axial compression. Simulated revision conditions showed no statistically significant differences compared with the primary implant condition, with the exception of flexion-extension range of motion where motions associated with the revised condition were significantly lower. Comparison of rotational and translation motions associated with the 7.5- and 10.75-mm implants showed no significant differences between the treatment conditions. CONCLUSIONS: These results indicate that implantation of laterally placed triangular titanium implants significantly reduces the motion of a sacroiliac joint using either the primary and revision sized implants. No statistically significant differences were detected when comparing the efficacy of primary, 7.5-mm revision, or 10.75-mm revision implants.

One-year performance of posterior narrow diameter implants in hyperglycemic and normo-glycemic patients-a pilot study.

OBJECTIVES: The aim of the study was to compare the performance of narrow diameter implants in patients with uncontrolled diabetes mellitus type 2 (T2DM) and normo-glycemic individuals during the first 12 months after implant loading. MATERIAL AND METHODS: In 16 T2DM patients with HbA1C > 6.5% (test group) and 16 normo-glycemic patients (HbA1C < 6.0%; control group), one to two narrow diameter tissue level implants were placed in the posterior maxilla or mandible. After 3-month lasting integration period, implants were loaded by fixed dentures. The clinical parameters probing depth (PD), bleeding on probing (BOP), attachment loss (CAL), recession and papilla bleeding index (PBI) were assessed manually at loading and after 12 months of function. The paired digital periapical radiographs were analyzed with regard to the change in marginal bone level (MBL) from baseline to 12 months' control. The mean values calculated for both patient groups were statistically analyzed. The technical complications were recorded. RESULTS: The T2DM group accounted 13 patients due to 3 dropouts. The overall implant survival rate after 12 months was 100%. The differences in means for the clinical parameters and the MBL were statistically non-significant between the T2DM and normo-glycemic patients for the short period of loaded function reported here. No technical complications were recorded. CONCLUSIONS: The study demonstrated an encouraging clinical outcome with narrow diameter implants in patients with uncontrolled T2DM compared to non-diabetics after 12 months post loading. For the short observation period, no biological and technical complications were reported regardless the glycemic status. CLINICAL RELEVANCE: Patients with HbA1C > 6.5% may benefit from the treatment with narrow diameter implants by avoiding complex surgical interventions with augmentation procedures. TRIAL REGISTRATION: Clinicaltrials.gov : NCT04630691.

Multiple sclerosis relapses contribute to long-term disability.

BACKGROUND: Treatments affect both relapse-related disability and short-term disability change, but measurements of their impact on long-term outcomes remain a challenge. OBJECTIVE: To ascertain the contribution of relapse-associated disability to overall disability in relapse-onset multiple sclerosis (RMS) using long-term data collected in our clinic. MATERIALS AND METHODS: Retrospective study of a cohort of newly diagnosed patients with RMS, (n = 176) was undertaken, measuring all confirmed changes in disability up to 15 years after onset. Worsening was assessed yearly and in 5-year epochs and was attributed to either relapse (RW) or slow progression (PW). RESULTS: At data lock, 139/176 (81%) of patients were still actively followed, with Expanded Disability Status Scale (EDSS) available for 10 years post-onset in 145/176 (82%) patients and 15 years post-onset EDSS in 83 patients (mean follow-up entire group 12.7 years post-onset). RW accounted for a large amount of worsening seen in the first 15 years of RMS. RW was less frequent over time, but accounted for most EDSS changes in the first decade of MS (167/267, 63% of EDSS changes), and remained important even in years 11-15 (17/50, 34% of EDSS changes). Median change in disability due to RW vs PW was similar over the entire 15 years. CONCLUSIONS: Worsening of treated MS was associated with relapses in many RMS patients throughout the first 15 years after onset, suggesting an opportunity for long-term benefit through relapse reduction.

Avaliação de desfechos após intervenção coronária percutânea com implante de stents farmacológicos em diabéticos multiarteriais: impacto incremental dos escores SYNTAX e SYNTAX residual em resultados clínicos de longo prazo / Outcome evaluation after angioplasty with drug-eluting stent implantation in multivessel diabetic patients: incremental impact of SYNTAX and residual SYNTAX scores on long-term clinical outcomes

Introdução: Apesar do advento dos stents farmacológicos (SF), diabéticos ainda experimentam risco aumentado de eventos cerebrovasculares e cardiovasculares maiores (ECCAM) após intervenção coronária percutânea (ICP). Nosso objetivo foi avaliar a incidência de ECCAM (óbito, acidente vascular cerebral, infarto agudo do miocárdio não fatal ou revascularização da lesão alvo) no seguimento de pelo menos 1 ano, além da capacidade de os escores SYNTAX e SYNTAX residual predizerem eventos. Métodos: Estudo unicêntrico, retrospectivo, de diabéticos com doença coronariana multiarterial, incluindo lesões de tronco de coronária esquerda (TCE), tratados com SF entre 2012 a 2014. Resultados: Foram incluídos 158 pacientes, com média de idades de 65,1 ± 9,1 anos. Em 44,2% dos casos, havia lesão proximal da artéria descendente anterior e 9% apresentavam lesão de TCE. A maioria dos procedimentos foi realizada com SF de segunda geração (91,1%). A média de seguimento foi de 1.054 ± 725 dias, e o ECCAM ocorreu em 17,4% dos pacientes. Entre aqueles com escore SYNTAX baixo (< 23), 10,2% apresentaram ECCAM, enquanto que entre os que foram categorizados como com SYNTAX moderado/alto (≥ 23), a incidência foi de 33,3% (p = 0,003). Dos pacientes com escore SYNTAX residual zero (revascularização completa), 7,5% evoluíram com ECCAM, comparados com 22,0% com revascularização incompleta (p = 0,01). Conclusões: O presente estudo aponta para a factibilidade e a segurança da realização de ICP em diabéticos multiarteriais, especialmente entre aqueles com baixa complexidade angiográfica. A revascularização incompleta foi preditora da maior ocorrência de ECCAM no seguimento de médio/longo prazo

Background: Despite the advent of drug-eluting stents (DES), diabetic patients still have increased risk of major adverse cardiovascular and cerebrovascular (MACCE) after percutaneous coronary intervention (PCI). Our aim was to evaluate the incidence of MACCE (death, stroke, non-fatal acute myocardial infarction, or target-lesion revascularization) during a follow-up of at least 1 year, in addition to the ability of the SYNTAX and residual SYNTAX scores to predict events. Methods: Single-center, retrospective study of diabetic patients with multivessel coronary disease, including left main coronary artery (LMCA) lesions treated with DES between 2012 and 2014. Results: A total of 158 patients were included, with a mean age of 65.1 ± 9.1 years. In 44.2% of the cases, there was a proximal lesion in the left anterior descending artery and 9% had a lesion in the LMCA. Most procedures were performed with second-generation DES (91.1%). Mean follow-up was 1,054 ± 725 days, and MACCE occurred in 17.4% of the patients. Among those with a low SYNTAX score (< 23), 10.2% had MACCE, while among those classified as having a moderate/high SYNTAX score (≥ 23), the incidence was 33.3% (p = 0.003). Of the patients with zero residual SYNTAX score (complete revascularization), 7.5% progressed with MACCE, compared with 22.0% with incomplete revascularization (p = 0.01). Conclusions: The present study points to the feasibility and safety of performing PCI in multivessel diabetic patients, especially among those with low angiographic complexity. Incomplete revascularization was a predictor of a higher occurrence of MACCE in the medium/long-term follow-up

Estudo OPTIMIZE: Subanálise dos Pacientes Tratados no Instituto Dante Pazzanese de Cardiologia / OPTIMIZE Trial: Subanalysis of Patients Treated at Instituto Dante Pazzanese de Cardiologia

Introdução: O OPTIMIZE constituiu um estudo prospectivo conduzido em 33 centros no Brasil, que randomizou pacientes para receber terapia antiplaquetária dupla por 3 ou 12 meses, após o implante de stents com eluição de zotarolimus. Nosso propósito foi avaliar os resultados dos pacientes tratados no Instituto Dante Pazzanese de Cardiologia e, posteriormente, compará-los aos de outros centros envolvidos do estudo. Métodos: Foram incluídos pacientes com angina estável ou síndrome coronariana aguda de baixo risco. O objetivo primário foi avaliar a incidência de eventos clínicos e cerebrais adversos, uma combinação de morte por qualquer causa, infarto agudo do miocárdio, acidente vascular encefálico ou sangramento maior aos 12 meses. Resultados: Entre abril de 2010 e março de 2012, incluímos 624 (20%) pacientes no OPTIMIZE. Aos 12 meses, não houve diferença significativa entre os grupos (3 vs. 12 meses de terapia antiplaquetária dupla) quanto à incidência de eventos clínicos e cerebrais adversos (3,8% vs. 6,7%; p = 0,15), eventos cardíacos adversos maiores (6,7% vs. 7,1%; p > 0,99) e nem de trombose do stent (0 vs. 1,3%; p = 0,12). O teste de heterogeneidade mostrou que a variabilidade observada nos resultados do Instituto Dante Pazzanese e dos outros centros não foi maior que a esperada para ocorrer por acaso ( p = 0,064). Conclusões : Nos pacientes ...

Background: OPTIMIZE was a prospective study conducted in 33 Brazilian sites that randomized patients to receive dual antiplatelet therapy for 3 or 12 months after zotarolimus eluting stent implantation. Our objective was to evaluate the outcomes of patients treated at Instituto Dante Pazzanese de Cardiologia and compare them to the outcomes of patients from other participating study sites. Methods: Patients with stable angina or low risk acute coronary syndrome were included in the study. The primary outcome was the incidence of adverse clinical and cerebral events, a composite of all cause of death, myocardial infarction, stroke, or major bleeding at 12 months. Results: Between April/2010 and March/2012, we included 624 (20%) patients in the OPTIMIZE study. At 12 months, there was no significant difference between groups (3 vs. 12 months of dual antiplatelet therapy) for net adverse clinical and cerebral events (3.8% vs. 6.7%; p = 0.15), major adverse cardiac events (6.7% vs. 7.1; p > 0.99) or stent thrombosis (0 vs. 1.3%; p = 0.12). The heterogeneity test showed that the variability observed in the results of Instituto Dante Pazzanese de Cardiologia and in the remaining sites was not greater than the expected to occur by chance (p = 0.064). Conclusions: In patients treated at Instituto Dante Pazzanese de Cardiologia, 3 months of dual antiplatelet therapy was not inferior to 12 months of therapy for the occurrence of net adverse clinical ...

Depressão e doença arterial coronariana: causa ou efeito? / Depression and coronary artery disease: cause or effect?

Introdução: A depressão é uma entidade clínica de prevalência crescente e impacto negativo de grande magnitude na sociedade. Sua relação com a doença arterial coronariana é provavelmente bidirecional, agindo como causa, agravante e efeito. Desenvolvimento: Diversos estudos foram publicados nas últimas duas décadas, com a intenção de elucidar as formas de interação entre essas duas doenças de grande prevalência. Até o momento, existem dados conclusivos de disfunção autonômica e endócrina, aumento de marcadores inflamatórios, disfunção endotelial e aumento de reatividade plaquetária como efeitos do estado depressivo...

The school community council: creating an environment for student success.

A model of community-school partnerships is developing within a school district in Evansville, Indiana. Based on a full-service community school philosophy, the model started in one elementary school in the Evansville-Vanderburgh School Corporation and has expanded into a districtwide initiative called the School Community Council. The council is made up of over seventy community organizations and social service agencies working together to establish full-service schools as places of community and to enhance youth and family development.