Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Fine particulate matter aggravates smoking induced lung injury via NLRP3/caspase-1 pathway in COPD.

BACKGROUND: Exposure to noxious particles, including cigarette smoke and fine particulate matter (PM2.5), is a risk factor for chronic obstructive pulmonary disease (COPD) and promotes inflammation and cell death in the lungs. We investigated the combined effects of cigarette smoking and PM2.5 exposure in patients with COPD, mice, and human bronchial epithelial cells. METHODS: The relationship between PM2.5 exposure and clinical parameters was investigated in patients with COPD based on smoking status. Alveolar destruction, inflammatory cell infiltration, and pro-inflammatory cytokines were monitored in the smoking-exposed emphysema mouse model. To investigate the mechanisms, cell viability and death and pyroptosis-related changes in BEAS-2B cells were assessed following the exposure to cigarette smoke extract (CSE) and PM2.5. RESULTS: High levels of ambient PM2.5 were more strongly associated with high Saint George's respiratory questionnaire specific for COPD (SGRQ-C) scores in currently smoking patients with COPD. Combined exposure to cigarette smoke and PM2.5 increased mean linear intercept and TUNEL-positive cells in lung tissue, which was associated with increased inflammatory cell infiltration and inflammatory cytokine release in mice. Exposure to a combination of CSE and PM2.5 reduced cell viability and upregulated NLRP3, caspase-1, IL-1ß, and IL-18 transcription in BEAS-2B cells. NLRP3 silencing with siRNA reduced pyroptosis and restored cell viability. CONCLUSIONS: PM2.5 aggravates smoking-induced airway inflammation and cell death via pyroptosis. Clinically, PM2.5 deteriorates quality of life and may worsen prognosis in currently smoking patients with COPD.

Sarcoid-like reaction in patients with malignant tumors: Long-term clinical course and outcomes.

Background: The development of non-caseating epithelioid cell granulomas in cancer patients who do not fulfill the systemic sarcoidosis criteria is termed sarcoid-like reaction (SLR). Little is known about this condition's natural course and impact on the prognosis of malignancy. We aimed to investigate the natural course and prognostic value of cancer-associated SLR. Methods: Clinical data were retrospectively analyzed in 32 patients with biopsy-proven cancer-associated SLR. Among patients with non-small cell lung cancer (NSCLC), SLR cases (n = 8) were matched with non-SLR cases (n = 78) for survival analysis. Results: Among the included patients, the mean age was 59.7 years, and 68.8% were female. The median follow-up period was 35.6 months [interquartile range (IQR): 14.0-61.4 months]. Of all the included malignancies (n = 32), breast cancer (25.0%) and NSCLC (25.0%) were the most common, with stage I being the most frequent tumor stage (59.4%). During follow-up, SLR progression to overt sarcoidosis was not observed. In the 28 patients with available follow-up computed tomography images (median interval: 24.9 months; IQR: 14.4-41.7), 4 patients received corticosteroids (n = 4), resulting to a decrease of SLR lesions. Meanwhile, among those who did not receive treatment (n = 24), the extent of SLR decreased or did not change in 85.7% of them, whereas 3.6% had increased SLR extent. Furthermore, among patients with NSCLC, SLR was not associated with overall survival [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 0.02-67.71, P = 0.882] and recurrence of malignancy (HR = 1.27, 95% CI 0.21-7.51, P = 0.793) in the Cox proportional hazard regression model. Conclusions: During the follow-up of cancer-related SLR, we found no further evidence for systemic sarcoidosis, and most of the lesions decreased or did not change. Development of SLR was also not associated with overall survival or disease-free survival in patients with NSCLC.

Hepatic GSK3ß-Dependent CRY1 Degradation Contributes to Diabetic Hyperglycemia.

Excessive hepatic glucose production (HGP) is a key factor promoting hyperglycemia in diabetes. Hepatic cryptochrome 1 (CRY1) plays an important role in maintaining glucose homeostasis by suppressing forkhead box O1 (FOXO1)-mediated HGP. Although downregulation of hepatic CRY1 appears to be associated with increased HGP, the mechanism(s) by which hepatic CRY1 dysregulation confers hyperglycemia in subjects with diabetes is largely unknown. In this study, we demonstrate that a reduction in hepatic CRY1 protein is stimulated by elevated E3 ligase F-box and leucine-rich repeat protein 3 (FBXL3)-dependent proteasomal degradation in diabetic mice. In addition, we found that GSK3ß-induced CRY1 phosphorylation potentiates FBXL3-dependent CRY1 degradation in the liver. Accordingly, in diabetic mice, GSK3ß inhibitors effectively decreased HGP by facilitating the effect of CRY1-mediated FOXO1 degradation on glucose metabolism. Collectively, these data suggest that tight regulation of hepatic CRY1 protein stability is crucial for maintaining systemic glucose homeostasis.

Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics.

In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. Although emerging evidence suggests that subpopulations of adipose stem cells (ASCs) would be important to explain fat depot differences, ASCs of two fat depots have not been comparatively investigated. Here, we characterized heterogeneous ASCs and examined the effects of intrinsic and tissue micro-environmental factors on distinct ASC features. We demonstrated that ASC subpopulations in EAT and IAT exhibited different molecular features with three adipogenic stages. ASC transplantation experiments revealed that intrinsic ASC features primarily determined their adipogenic potential. Upon obesogenic stimuli, EAT-specific SDC1+ ASCs promoted fibrotic remodeling, whereas IAT-specific CXCL14+ ASCs suppressed macrophage infiltration. Moreover, IAT-specific BST2high ASCs exhibited a high potential to become beige adipocytes. Collectively, our data broaden the understanding of ASCs with new insights into the origin of white fat depot differences.

The Impact of Air Pollutants and Meteorological Factors on Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Study.

Rationale: Chronic obstructive lung disease (COPD) is a chronic progressive disease. Although smoking is the most important risk factor, 30% of patients with COPD are never-smokers, and environmental agents are also influential. The effects of air pollutants and meteorological factors on COPD exacerbations have not been studied extensively. Objectives: We aimed to investigate the air pollutants and meteorological factors that impact the incidence of COPD exacerbations. Methods: We obtained clinical data of COPD exacerbation cases from The National Health Insurance Service and merged it with 24-hour average values of air pollutants and meteorological factors from national databases. Patients who reside in eight metropolitan cities, where observatory stations are densely located, were selected for analysis. Results: In 1,404,505 patients with COPD between 2013 and 2018, 15,282 COPD exacerbations leading to hospitalization or emergency room visits were identified. Among the various air pollutants and meteorological factors, particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5), particulate matter ⩽10 µm in aerodynamic diameter (PM10), NO2, SO2, CO, O3, average temperature, and diurnal temperature range (DTR) were associated with COPD exacerbations. Generalized additive mode model analysis with cubic splines showed an inverted U-shaped relationship with PM2.5, PM10, CO, NO2, SO2, O3, DTR, and humidity, whereas it displayed a U-shaped pattern with the average temperature. Distinct patterns were found from 2015-2016 to 2017-2018. Conclusions: PM2.5, PM10, CO, NO2, O3, SO2, average temperature, humidity, and DTR affected the incidence of COPD exacerbations in various patterns, up to 10 lag days.

Roles of IκB kinases and TANK-binding kinase 1 in hepatic lipid metabolism and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is strongly associated with obesity-related ectopic fat accumulation in the liver. Hepatic lipid accumulation encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Given that dysregulated hepatic lipid metabolism may be an onset factor in NAFLD, understanding how hepatic lipid metabolism is modulated in healthy subjects and which steps are dysregulated in NAFLD subjects is crucial to identify effective therapeutic targets. Additionally, hepatic inflammation is involved in chronic hepatocyte damage during NAFLD progression. As a key immune signaling hub that mediates NF-κB activation, the IκB kinase (IKK) complex, including IKKα, IKKß, and IKKγ (NEMO), has been studied as a crucial regulator of the hepatic inflammatory response and hepatocyte survival. Notably, TANK-binding kinase 1 (TBK1), an IKK-related kinase, has recently been revealed as a potential link between hepatic inflammation and energy metabolism. Here, we review (1) the biochemical steps of hepatic lipid metabolism; (2) dysregulated lipid metabolism in obesity and NAFLD; and (3) the roles of IKKs and TBK1 in obesity and NAFLD.

Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity.

In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.

Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility.

Does the Risk of Metabolic Syndrome Increase in Thyroid Cancer Survivors?

BACKGROUND: The steep rise in thyroid cancer observed in recent decades has caused an increase in the population of long-term thyroid cancer survivors. Other than recurrences of cancer, the long-term health consequences of surviving thyroid cancer, particularly metabolic syndrome, have not yet been determined. The aim of this study was to estimate the risk of metabolic syndrome in thyroid cancer survivors. MATERIALS AND METHODS: Population-based data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used for the analysis. The data of KNHANES IV-VI from 2007-2014 were obtained. After excluding subjects who were under 19 years old, whose fasting interval was less than 8 hours, and whose data for predefined variables including metabolic syndrome components were incomplete, 34,347 subjects were analyzed. The incidence of metabolic syndrome and its components were evaluated in three groups: subjects with no history of thyroid cancer, subjects diagnosed with thyroid cancer within 3 years of the survey date, and subjects diagnosed more than 3 years before the survey date. RESULTS: Thyroid cancer diagnoses were made within 3 years of the survey date for 95 subjects (group 1, short-term survivors) and more than 3 years earlier than the survey date for 60 subjects (group 2, long-term survivors). Metabolic syndrome was frequently observed with clinical significance (odds ratio [OR] 1.986 [95% confidence interval [CI] 1.0-3.70], p = 0.030) in short-term survivors compared with subjects with no thyroid cancer history. Risks for having high blood pressure and high fasting glucose were estimated to be higher in the short-term survivor group (OR 2.115 [CI 1.23-3.64], p = 0.006 and OR 1.792 [CI 1.03-3.11], p = 0.038, respectively). No significant associations were noticed in the long-term survivor group when compared with the group with no thyroid cancer history. CONCLUSION: Risks for metabolic syndrome, especially high blood pressure and high fasting glucose, were increased in short-term survivors of thyroid cancer but not in long-term survivors when compared with subjects with no history of thyroid cancer.

Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity.

Adipose tissue inflammation is an important factor in obesity that promotes insulin resistance. Among various cell types in adipose tissue, immune cells actively regulate inflammatory responses and affect whole-body energy metabolism. In particular, invariant natural killer T (iNKT) cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesity-induced inflammation in adipose tissue. However, the molecular mechanisms by which adipose iNKT cells become activated and mediate anti-inflammatory roles in obese adipose tissue have not been thoroughly understood yet. In the current study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. Accordingly, adipocyte-specific CD1d-knockout (CD1dADKO) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide-induced iNKT cell activation. Additionally, HFD-fed CD1dADKO mice revealed reduced interleukin-4 expression in adipose iNKT cells and aggravated adipose tissue inflammation and insulin resistance. Collectively, these data suggest that adipocytes could selectively stimulate adipose iNKT cells to mediate anti-inflammatory responses and attenuate excess proinflammatory responses in obese adipose tissue.

Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity.

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

PIASy-mediated sumoylation of SREBP1c regulates hepatic lipid metabolism upon fasting signaling.

SREBP1c is a key transcription factor that regulates de novo lipogenesis during anabolic periods. However, the molecular mechanisms involved in the suppression of SREBP1c under nutritional deprivation are largely unknown. In this study, we demonstrate that the small ubiquitin-related modifier (SUMO) E3 ligase, a protein inhibitor of activated STAT Y (PIASy), sumoylates SREBP1c at Lys98, leading to suppression of the hepatic lipogenic program upon fasting-induced signals. In primary hepatocytes, ablation of PIASy stimulated intracellular lipid accumulation through the induction of SREBP1c and its target genes. Given that protein kinase A (PKA) plays important roles in catabolic responses, activated PKA enhances the sumoylation of SREBP1c and potentiates the interaction between SREBP1c and PIASy. Notably, overexpression of PIASy in obese db/db mice ameliorated hepatic steatosis, while suppression of PIASy in lean (wild-type) mice stimulated hepatic lipogenesis with increased expression of SREBP1c target genes. Furthermore, PKA-mediated SREBP1c phosphorylation augmented SREBP1c sumoylation, subsequently leading to degradation of SREBP1c via ubiquitination. Together, these data suggest that PKA-induced SREBP1c sumoylation by PIASy is a key regulatory mechanism to turn off hepatic lipogenesis during nutritional deprivation.

Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance.

OBJECTIVE: Tissue inflammation is a key factor underlying insulin resistance in established obesity. Several models of immuno-compromised mice are protected from obesity-induced insulin resistance. However, it is unanswered whether inflammation triggers systemic insulin resistance or vice versa in obesity. The purpose of this study was to assess these questions. RESEARCH DESIGN AND METHODS: We fed a high-fat diet (HFD) to wild-type mice and three different immuno-compromised mouse models (lymphocyte-deficient Rag1 knockout, macrophage-depleted, and hematopoietic cell-specific Jun NH(2)-terminal kinase-deficient mice) and measured the time course of changes in macrophage content, inflammatory markers, and lipid accumulation in adipose tissue, liver, and skeletal muscle along with systemic insulin sensitivity. RESULTS: In wild-type mice, body weight and adipose tissue mass, as well as insulin resistance, were clearly increased by 3 days of HFD. Concurrently, in the short-term HFD period inflammation was selectively elevated in adipose tissue. Interestingly, however, all three immuno-compromised mouse models were not protected from insulin resistance induced by the short-term HFD. On the other hand, lipid content was markedly increased in liver and skeletal muscle at day 3 of HFD. CONCLUSIONS: These data suggest that the initial stage of HFD-induced insulin resistance is independent of inflammation, whereas the more chronic state of insulin resistance in established obesity is largely mediated by macrophage-induced proinflammatory actions. The early-onset insulin resistance during HFD feeding is more likely related to acute tissue lipid overload.

Adipocytokine orosomucoid integrates inflammatory and metabolic signals to preserve energy homeostasis by resolving immoderate inflammation.

Orosomucoid (ORM), also called alpha-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose Orm levels were elevated by metabolic signals, including insulin, high glucose, and free fatty acid, as well as by the proinflammatory cytokine tumor necrosis factor-alpha, which is found in increased levels in the adipose tissue of morbid obese subjects. In both adipocytes and macrophages, ORM suppressed proinflammatory gene expression and pathways such as NF-kappaB and mitogen-activated protein kinase signalings and reactive oxygen species generation. Concomitantly, ORM relieved hyperglycemia-induced insulin resistance as well as tumor necrosis factor-alpha-mediated lipolysis in adipocytes. Accordingly, ORM improved glucose and insulin tolerance in obese and diabetic db/db mice. Taken together, our results suggest that ORM integrates inflammatory and metabolic signals to modulate immune responses to protect adipose tissue from excessive inflammation and thereby from metabolic dysfunction.

Berberine suppresses proinflammatory responses through AMPK activation in macrophages.

Berberine (BBR) has been shown to improve several metabolic disorders, such as obesity, type 2 diabetes, and dyslipidemia, by stimulating AMP-activated protein kinase (AMPK). However, the effects of BBR on proinflammatory responses in macrophages are poorly understood. Here we show that BBR represses proinflammatory responses through AMPK activation in macrophages. In adipose tissue of obese db/db mice, BBR treatment significantly downregulated the expression of proinflammatory genes such as TNF-alpha, IL-1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Consistently, BBR inhibited LPS-induced expression of proinflammatory genes including IL-1beta, IL-6, iNOS, MCP-1, COX-2, and matrix metalloprotease-9 in peritoneal macrophages and RAW 264.7 cells. Upon various proinflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs, such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages. Moreover, these inhibitory effects of BBR on proinflammatory responses were abolished by AMPK inhibition via either compound C, an AMPK inhibitor, or dominant-negative AMPK, implying that BBR would downregulate proinflammatory responses in macrophages via AMPK stimulation.

Vertical alveolar ridge augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement.

OBJECTIVE: The aim of this study was to evaluate the combined use of autogenous bone and platelet-enriched fibrin glue as grafting material for vertical alveolar ridge augmentation with simultaneous implant placement in a canine alveolar ridge defect model. STUDY DESIGN: In 6 mongrel dogs, bilateral vertical alveolar ridge defects were created in the mandible. After 3 months of healing, 2 dental implants were placed in each defect of the mandible, creating 6-mm supra-alveolar peri-implant defects. The 2 implants per defect were subjected to surgical treatments involving either a combination of autogenous bone grafts and platelet-enriched fibrin glue, or a conventional flap procedure only (control). After a healing period of 6 months, the dogs were humanely killed for histological and histometric analyses. RESULTS: Implant placement alone produced limited vertical alveolar height (0.6 +/- 0.4 mm). However, alveolar augmentation including a combination of autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement resulted in alveolar ridge augmentation amounting to 4.2 +/- 1.0 mm, comprising 63% of the defect height. New bone-implant contact was 40.5% in the defects treated with combined autogenous bone grafts and platelet-enriched fibrin glue, and was 48.4% in the resident bone; this difference was not statistically significant. CONCLUSION: The present study demonstrates that vertical alveolar ridge augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement might effectively increase vertical alveolar ridge height and allow for an acceptable level of osseointegration.

Maxillary sinus floor augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement.

OBJECTIVE: The aim of this study was to evaluate the use of autogenous bone in combination with platelet-enriched fibrin glue as a grafting material for maxillary sinus augmentation with simultaneous implant placement in dogs. STUDY DESIGN: The mucous membranes of 12 sinuses in 6 dogs were elevated bilaterally. In the right sinus, autogenous bone mixed with platelet-enriched fibrin glue was grafted into the space between the membrane and the sinus wall. In the left sinus, autogenous bone alone was grafted as a control. At the same time, 2 dental implants were inserted into the grafting material through the maxillary sinus floor. The animals were killed 6 months after surgery. RESULTS: The mean bone-implant contact was 40.5% on the fibrin glue side and 32.3% on the control side (P < .05). The mean height of newly formed bone in the augmented area was 12.2 mm on the fibrin glue side and 10.7 mm on the control side (P < .05). CONCLUSION: The results indicate that the use of autogenous bone mixed with platelet-enriched fibrin glue can achieve results superior to those for grafts of autogenous bone alone. The specific improvements of this technique include enhanced osseointegration of dental implants and increased height of new bone.