Impact of autologous platelet concentrates on the osseointegration of dental implants.

Osseointegration is defined as the direct deposition of bone onto biomaterial devices, most commonly composed from titanium, for the purpose of anchoring dental prostheses. The use of autologous platelet concentrates (APC) has the potential to enhance this process by modifying the interface between the host and the surface of the titanium implant. The rationale is to modify the implant surface and implant-bone interface via "biomimicry," a process whereby the deposition of the host's own proteins and extracellular matrix enhances the biocompatibility of the implant and hence accelerates the osteogenic healing process. This review of the available evidence reporting on the effect of APC on osseointegration explores in vitro laboratory studies of the interaction of APC with different implant surfaces, as well as the in vivo and clinical effects of APC on osseointegration in animal and human studies. The inherent variability associated with using autologous products, namely the unique composition of each individual's blood plasma, as well as the great variety in APC protocols, combination of biomaterials, and clinical/therapeutic application, makes it is difficult to make any firm conclusions about the in vivo and clinical effects of APC on osseointegration. The available evidence suggests that the clinical benefits of adding PRP and the liquid form of L-PRF (liquid fibrinogen) to any implant surface appear to be limited. The application of L-PRF membranes in the osteotomy site, however, may produce positive clinical effects at the early stage of healing (up to 6 weeks), by promoting early implant stability and reducing marginal bone loss, although no positive longer term effects were observed. Careful interpretation and cautious conclusions should be drawn from these findings as there were various limitations in methodology. Future studies should focus on better understanding of the influence of APCs on the biomaterial surface and designing controlled preclinical and clinical studies using standardized APC preparation and application protocols.

Evaluating models and assessment techniques for understanding oral biofilm complexity.

Oral biofilms are three-dimensional (3D) complex entities initiating dental diseases and have been evaluated extensively in the scientific literature using several biofilm models and assessment techniques. The list of biofilm models and assessment techniques may overwhelm a novice biofilm researcher. This narrative review aims to summarize the existing literature on biofilm models and assessment techniques, providing additional information on selecting an appropriate model and corresponding assessment techniques, which may be useful as a guide to the beginner biofilm investigator and as a refresher to experienced researchers. The review addresses previously established 2D models, outlining their advantages and limitations based on the growth environment, availability of nutrients, and the number of bacterial species, while also exploring novel 3D biofilm models. The growth of biofilms on clinically relevant 3D models, particularly melt electrowritten fibrous scaffolds, is discussed with a specific focus that has not been previously reported. Relevant studies on validated oral microcosm models that have recently gaining prominence are summarized. The review analyses the advantages and limitations of biofilm assessment methods, including colony forming unit culture, crystal violet, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt assays, confocal microscopy, fluorescence in situ hybridization, scanning electron microscopy, quantitative polymerase chain reaction, and next-generation sequencing. The use of more complex models with advanced assessment methodologies, subject to the availability of equipment/facilities, may help in developing clinically relevant biofilms and answering appropriate research questions.

Fabrication and characterization of a 3D polymicrobial microcosm biofilm model using melt electrowritten scaffolds.

The majority of current biofilm models or substrates are two-dimensional (2D) and support biofilm growth in the horizontal plane only. Three-dimensional (3D) substrates may support both horizontal and vertical biofilm growth. This study compared biofilm growth quantity and quality between highly porous 3D micrometric fibrous scaffolds and 2D film substrates fabricated from medical grade polycaprolactone (mPCL). Melt electrowriting (MEW), a high-resolution additive manufacturing technology, was employed to design orderly aligned fine (~12 µm) fibre-based 3D scaffolds, while 2D films were fabricated by a casting method. The 3D scaffolds with a controlled pore size of 100 and 250 µm and thickness of ~0.8 mm and 2D films were incubated in pooled saliva collected from six volunteers for 1, 2, 4, 7 and 10 days at 37 °C to facilitate polymicrobial biofilm formation. Crystal violet assay demonstrated greater biofilm biomass in 3D MEW scaffolds than in 2D films. Biofilm thickness in 3D scaffolds was significantly higher compared to the biofilm thickness in 2D films. Both biovolume and substratum coverage of the biofilms was higher in the 3D scaffolds compared to 2D films. Polymeric bridges, pores, and channels characteristic of biofilms could be demonstrated by scanning electron microscopy. 16S rRNA sequencing demonstrated that the polymicrobial biofilms in the 3D scaffolds were able to retain 60-70 % of the original inoculum microbiome after 4 days. The MEW-fabricated 3D fibrous scaffold is a promising substrate for supporting multidirectional biofilm growth and modelling of a polymicrobial microcosm.

Surgical gestures as a method to quantify surgical performance and predict patient outcomes.

How well a surgery is performed impacts a patient's outcomes; however, objective quantification of performance remains an unsolved challenge. Deconstructing a procedure into discrete instrument-tissue "gestures" is a emerging way to understand surgery. To establish this paradigm in a procedure where performance is the most important factor for patient outcomes, we identify 34,323 individual gestures performed in 80 nerve-sparing robot-assisted radical prostatectomies from two international medical centers. Gestures are classified into nine distinct dissection gestures (e.g., hot cut) and four supporting gestures (e.g., retraction). Our primary outcome is to identify factors impacting a patient's 1-year erectile function (EF) recovery after radical prostatectomy. We find that less use of hot cut and more use of peel/push are statistically associated with better chance of 1-year EF recovery. Our results also show interactions between surgeon experience and gesture types-similar gesture selection resulted in different EF recovery rates dependent on surgeon experience. To further validate this framework, two teams independently constructe distinct machine learning models using gesture sequences vs. traditional clinical features to predict 1-year EF. In both models, gesture sequences are able to better predict 1-year EF (Team 1: AUC 0.77, 95% CI 0.73-0.81; Team 2: AUC 0.68, 95% CI 0.66-0.70) than traditional clinical features (Team 1: AUC 0.69, 95% CI 0.65-0.73; Team 2: AUC 0.65, 95% CI 0.62-0.68). Our results suggest that gestures provide a granular method to objectively indicate surgical performance and outcomes. Application of this methodology to other surgeries may lead to discoveries on methods to improve surgery.

Impact of Patient, Surgical, and Perioperative Factors on Discharge Disposition after Radical Cystectomy.

Radical cystectomy (RC) is a complex procedure associated with lengthy hospital stays and high complication and readmission rates. We evaluated the impact of patient, surgical, and perioperative factors on discharge disposition following RC at a tertiary referral center. From 2012 to 2019, all bladder cancer patients undergoing RC at our institution were identified (n = 1153). Patients were classified based on discharge disposition: to home or to continued facility-based rehabilitation centers (CFRs, n = 180 (15.61%) patients). On multivariate analysis of patient factors only, age [Risk Ratio (RR): 1.07, p < 0.001)], single marital status (RR: 1.09, p < 0.001), and living alone prior to surgery (RR: 2.55, p = 0.004) were significant predictors of discharge to CFRs. Multivariate analysis of patient, surgical, and perioperative factors indicated age (RR: 1.09, p < 0.001), single marital status (RR: 3.9, p < 0.001), living alone prior to surgery (RR: 2.42, p = 0.01), and major post-operative (Clavien > 3) complications (RR: 3.44, p < 0.001) were significant independent predictors of discharge to CFRs. Of note, ERAS did not significantly impact discharge disposition. Specific patient and perioperative factors significantly impact discharge disposition. Patients who are older, living alone prior to surgery, and/or have a major post-operative complication are more likely to be discharged to CFRs after RC.

Simulated and clinical aerosol spread in common periodontal aerosol-generating procedures.

OBJECTIVES: This study evaluated particle spread associated with various common periodontal aerosol-generating procedures (AGPs) in simulated and clinical settings. MATERIALS AND METHODS: A simulation study visualized the aerosols, droplets, and splatter spread with and without high-volume suction (HVS, 325 L/min) during common dental AGPs, namely ultrasonic scaling, air flow prophylaxis, and implant drilling after fluorescein dye was added to the water irrigant as a tracer. Each procedure was repeated 10 times. A complementary clinical study measured the spread of contaminated particles within the dental operatory and quantified airborne protein dispersion following 10 min of ultrasonic supragingival scaling of 19 participants during routine periodontal treatment. RESULTS: The simulation study data showed that air flow produced the highest amount of splatters and the ultrasonic scaler generated the most aerosol and droplet particles at 1.2 m away from the source. The use of HVS effectively reduced 37.5-96% of splatter generation for all three dental AGPs, as well as 82-93% of aerosol and droplet particles at 1.2 m for the ultrasonic scaler and air polisher. In the clinical study, higher protein levels above background levels following ultrasonic supragingival scaling were detected in fewer than 20% of patients, indicating minimal particle spread. CONCLUSIONS: While three common periodontal AGPs produce aerosols and droplet particles up to at least 1.2 m from the source, the use of HVS is of significant benefit. Routine ultrasonic supragingival scaling produced few detectable traces of salivary protein at various sites throughout the 10-min dental operatory. CLINICAL RELEVANCE: The likelihood of aerosol spread to distant sites during common periodontal AGPs is greatly reduced by high-volume suction. Clinically, limited evidence of protein contaminants was found following routine ultrasonic scaling, suggesting that the the majority of the contamination consisits of the irrigant rather than organic matter from the oral cavity.

Tailored Feedback Based on Clinically Relevant Performance Metrics Expedites the Acquisition of Robotic Suturing Skills-An Unblinded Pilot Randomized Controlled Trial.

PURPOSE: Previously, we identified 8 objective suturing performance metrics highly predictive of urinary continence recovery after robotic-assisted radical prostatectomy. Here, we aimed to test the feasibility of providing tailored feedback based upon these clinically relevant metrics and explore the impact on the acquisition of robotic suturing skills. MATERIALS AND METHODS: Training surgeons were recruited and randomized to a feedback group or a control group. Both groups completed a baseline, midterm and final dry laboratory vesicourethral anastomosis (VUA) and underwent 4 intervening training sessions each, consisting of 3 suturing exercises. Eight performance metrics were recorded during each exercise: 4 automated performance metrics (derived from kinematic and system events data of the da Vinci® Robotic System) representing efficiency and console manipulation competency, and 4 suturing technical skill scores. The feedback group received tailored feedback (a visual diagram+verbal instructions+video examples) based on these metrics after each session. Generalized linear mixed model was used to compare metric improvement (Δ) from baseline to the midterm and final VUA. RESULTS: Twenty-three participants were randomized to the feedback group (11) or the control group (12). Demographic data and baseline VUA metrics were comparable between groups. The feedback group showed greater improvement than the control group in aggregate suturing scores at midterm (mean Δ feedback group 4.5 vs Δ control group 1.1) and final VUA (Δ feedback group 5.3 vs Δ control group 4.9). The feedback group also showed greater improvement in the majority of the included metrics at midterm and final VUA. CONCLUSIONS: Tailored feedback based on specific, clinically relevant performance metrics is feasible and may expedite the acquisition of robotic suturing skills.

Machine Learning to Delineate Surgeon and Clinical Factors That Anticipate Positive Surgical Margins After Robot-Assisted Radical Prostatectomy.

Purpose: Automated performance metrics (APMs), derived from instrument kinematic and systems events data during robotic surgery, are validated objective measures of surgeon performance. Our previous studies showed that APMs are strong outcome predictors of urinary continence after robot-assisted radical prostatectomy (RARP). We now use machine learning to investigate how surgeon performance (i.e., APMs) and clinical factors can predict positive surgical margins (PSMs) after RARP. Methods: We prospectively collected data of patients undergoing RARP at our institution from 2016 to 2019. Random Forest model predicted PSMs based on 15 clinical factors and 38 APMs from 11 standardized RARP steps. Out-of-bag Gini impurity index determined the top 10 variables of importance (VOI). APMs in the top 10 VOI were assessed for confounding effects by extracapsular extension (ECE) and pathologic T (pT) through Poisson regression with Generalized Estimating Equation. Results: 55/236 (23.3%) cases had PSMs. Of the 55 cases with PSMs, 9 (16.4%) were pT2 and 46 (83.6%), pT3. The full model, including clinical factors and APMs, achieved area under the curve (AUC) 0.74. When assessing clinical factors or APMs alone, the model achieved AUC 0.72 and 0.64, respectively. The strongest PSM predictors were ECE and pT stage, followed by APMs in specific steps. After adjusting for ECE and pT stage, most APMs remained as independent predictors of PSM. Conclusion: Using machine learning methods, we found that the strongest predictors of PSMs after RARP are nonmodifiable, disease-driven factors (ECE and pT). While APMs provide minimal additional insight into when PSMs may occur, they are nonetheless capable of independently predicting PSMs based on objective measures of surgeon performance.

Influence of Bioinspired Lithium-Doped Titanium Implants on Gingival Fibroblast Bioactivity and Biofilm Adhesion.

Soft tissue integration (STI) at the transmucosal level around dental implants is crucial for the long-term success of dental implants. Surface modification of titanium dental implants could be an effective way to enhance peri-implant STI. The present study aimed to investigate the effect of bioinspired lithium (Li)-doped Ti surface on the behaviour of human gingival fibroblasts (HGFs) and oral biofilm in vitro. HGFs were cultured on various Ti surfaces-Li-doped Ti (Li_Ti), NaOH_Ti and micro-rough Ti (Control_Ti)-and were evaluated for viability, adhesion, extracellular matrix protein expression and cytokine secretion. Furthermore, single species bacteria (Staphylococcus aureus) and multi-species oral biofilms from saliva were cultured on each surface and assessed for viability and metabolic activity. The results show that both Li_Ti and NaOH_Ti significantly increased the proliferation of HGFs compared to the control. Fibroblast growth factor-2 (FGF-2) mRNA levels were significantly increased on Li_Ti and NaOH_Ti at day 7. Moreover, Li_Ti upregulated COL-I and fibronectin gene expression compared to the NaOH_Ti. A significant decrease in bacterial metabolic activity was detected for both the Li_Ti and NaOH_Ti surfaces. Together, these results suggest that bioinspired Li-doped Ti promotes HGF bioactivity while suppressing bacterial adhesion and growth. This is of clinical importance regarding STI improvement during the maintenance phase of the dental implant treatment.

COVID-19 in pregnancy: a systematic review of chest CT findings and associated clinical features in 427 patients.

PURPOSE: Our purpose was to conduct a comprehensive systematic review of all existing literature regarding imaging findings on chest CT and associated clinical features in pregnant patients diagnosed with COVID-19. MATERIALS & METHODS: A literature search was conducted on April 21, 2020 and updated on July 24, 2020 using PubMed, Embase, World Health Organization, and Google Scholar databases. Only studies which described chest CT findings of COVID-19 in pregnant patients were included for analysis. RESULTS: A total of 67 articles and 427 pregnant patients diagnosed with COVID-19 were analyzed. The most frequently encountered pulmonary findings on chest CT were ground-glass opacities (77.2%, 250/324), posterior lung involvement (72.5%, 50/69), multilobar involvement (71.8%, 239/333), bilateral lung involvement (69.4%, 231/333), peripheral distribution (68.1%, 98/144), and consolidation (40.9%, 94/230). Pregnant patients were also found to present more frequently with consolidation (40.9% vs. 21.0-31.8%) and pleural effusion (30.0% vs. 5.0%) in comparison to the general population. Associated clinical features included antepartum fever (198 cases), lymphopenia (128 cases), and neutrophilia (97 cases). Of the 251 neonates delivered, 96.8% had negative RT-PCR and/or IgG antibody testing for COVID-19. In the eight cases (3.2%) of reported neonatal infection, tests were either conducted on samples collected up to 72 h after birth or were found negative on all subsequent RT-PCR tests. CONCLUSION: Pregnant patients appear to present more commonly with more advanced COVID-19 CT findings compared to the general adult population. Furthermore, characteristic laboratory abnormalities found in pregnant patients tended to mirror those found in the general patient population. Lastly, results from neonatal testing suggest a low risk of vertical transmission.

Timing, Patterns and Predictors of 90-Day Readmission Rate after Robotic Radical Cystectomy.

PURPOSE: We examine the timing, patterns and predictors of 90-day readmission after robotic radical cystectomy. MATERIALS AND METHODS: From September 2009 to March 2017, 271 consecutive patients undergoing robotic radical cystectomy with intent to cure bladder cancer (intracorporeal diversion 253, 93%) were identified from our prospectively collated institutional database. Readmission was defined as any subsequent inpatient admission or unplanned visit occurring within 90 days from discharge after the index hospitalization. Multiple readmissions were defined as 2 or more readmissions within a 90-day period. Logistic regression analysis was used to identify independent factors related to single and multiple 90-day readmissions. RESULTS: A total of 78 (28.8%) patients were readmitted at least once within 90 days after discharge, of whom 20 (25.6%) reported multiple readmissions. The cumulative duration of readmission was 6.2 (6.17) days with 6 (7.6%) patients having less than 24 hours readmission. Metabolic, infectious, genitourinary and gastrointestinal complications were identified as the primary cause of readmission in 39.5%, 23.5%, 22.3% and 17%, respectively. Fifty percent of readmissions occurred in the first 2 weeks after hospital discharge. On multivariable logistic regression analysis in-hospital infections (OR 2.85, p=0.001) were independent predictors for overall readmission. Male gender (OR 3.5, p=0.02) and in-hospital infections (OR 4.35, p=0.002) were independent predictors for multiple readmissions. CONCLUSIONS: The 90-day readmission rate following robotic radical cystectomy is significant. In-hospital infections and male gender were independent factors for readmission. Most readmissions occurred in the first 2 weeks following discharge, with metabolic derangements and infections being the most common causes.

Re-establishment of macrophage homeostasis by titanium surface modification in type II diabetes promotes osseous healing.

Titanium surface mediated immunomodulation may address compromised post-implantation bone healing in diabetes mellitus. To assess in vitro phenotypic changes, M1 and M2 polarised Type 2 diabetic rat (Goto Kakizaki, GK) macrophages were cultured on micro-rough (SLA) or hydrophilic nanostructured SLA (modSLA) titanium. The in vivo effects of the SLA and modSLA surfaces on macrophage phenotype, wound-associated protein expression and bone formation were investigated using a critical-sized calvarial defect model. Compared to healthy macrophages, GK M2 macrophage function was compromised, secreting significantly lower levels of the anti-inflammatory cytokine IL-10. The modSLA surface attenuated the pro-inflammatory cellular environment, reducing pro-inflammatory cytokine production and promoting M2 macrophage phenotype differentiation. ModSLA also suppressed gene expression associated with macrophage multinucleation and giant cell formation and stimulated pro-osteogenic genes in co-cultured osteoblasts. In vivo, modSLA enhanced osteogenesis compared to SLA in GK rats. During early healing, proteomic analysis of both surface adherent and wound exudate material showed that modSLA promoted an immunomodulatory pro-reparative environment. The modSLA surface therefore successfully compensated for the compromised M2 macrophage function in Type 2 diabetes by attenuating the pro-inflammatory response and promoting M2 macrophage activity, thus restoring macrophage homeostasis and resulting in a cellular environment favourable for enhanced osseous healing.

In vivo bone regeneration assessment of offset and gradient melt electrowritten (MEW) PCL scaffolds.

BACKGROUND: Biomaterial-based bone tissue engineering represents a promising solution to overcome reduced residual bone volume. It has been previously demonstrated that gradient and offset architectures of three-dimensional melt electrowritten poly-caprolactone (PCL) scaffolds could successfully direct osteoblast cells differentiation toward an osteogenic lineage, resulting in mineralization. The aim of this study was therefore to evaluate the in vivo osteoconductive capacity of PCL scaffolds with these different architectures. METHODS: Five different calcium phosphate (CaP) coated melt electrowritten PCL pore sized scaffolds: 250 µm and 500 µm, 500 µm with 50% fibre offset (offset.50.50), tri layer gradient 250-500-750 µm (grad.250top) and 750-500-250 µm (grad.750top) were implanted into rodent critical-sized calvarial defects. Empty defects were used as a control. After 4 and 8 weeks of healing, the new bone was assessed by micro-computed tomography and immunohistochemistry. RESULTS: Significantly more newly formed bone was shown in the grad.250top scaffold 8 weeks post-implantation. Histological investigation also showed that soft tissue was replaced with newly formed bone and fully covered the grad.250top scaffold. While, the bone healing did not happen completely in the 250 µm, offset.50.50 scaffolds and blank calvaria defects following 8 weeks of implantation. Immunohistochemical analysis showed the expression of osteogenic markers was present in all scaffold groups at both time points. The mineralization marker Osteocalcin was detected with the highest intensity in the grad.250top and 500 µm scaffolds. Moreover, the expression of the endothelial markers showed that robust angiogenesis was involved in the repair process. CONCLUSIONS: These results suggest that the gradient pore size structure provides superior conditions for bone regeneration.

Hydrophilic titanium surface-induced macrophage modulation promotes pro-osteogenic signalling.

OBJECTIVES: As biomaterial-induced modulation of mediators of the immune response may be a potential therapeutic approach to enhance wound healing events, the aim of this study was to delineate the effects of titanium surface modification on macrophage phenotype and function. MATERIAL AND METHODS: Rodent bone marrow-derived macrophages were polarized into M1 and M2 phenotypes and cultured on micro-rough (SLA) and hydrophilic modified SLA (modSLA) titanium discs. Macrophage phenotype and cytokine secretion were subsequently assessed by immunostaining and ELISA, respectively. Osteoblast gene expression in response to culture in the M1 and M2 macrophage conditioned media was also evaluated over 7 days by RT-PCR. RESULTS: M1 macrophage culture on the modSLA surface promoted an M2-like phenotype as demonstrated by marked CD163 protein expression, Arg1 gene expression and the secretion of cytokines that significantly upregulated in osteoblasts the expression of genes associated with the TGF-ß/BMP signalling pathway and osteogenesis. In comparison, M2 macrophage culture on SLA surface promoted an inflammatory phenotype and cytokine profile that was not conducive for osteogenic gene expression. CONCLUSIONS: Macrophages are able to alter or switch their phenotype according to the signals received from the biomaterial surface. A hydrophilic micro-rough titanium surface topography elicits a macrophage phenotype associated with reduced inflammation and enhanced pro-osteogenic signalling.

The influence of high-dose systemic zoledronate administration on osseointegration of implants with different surface topography.

AIM: To evaluate the influence of systemic zoledronate administration on the osseointegration of titanium implants with different surface topography in rat maxillae. METHODS: Twenty Sprague-Dawley rats were divided into two groups-test (bisphosphonate) and control (healthy). Bisphosphonate administration began three weeks prior to implant placement, and the animals received zoledronate (66 µg/kg) three times per week. Forty endosseous implants with a moderately rough (20 implants) or a turned surface (20 implants) were immediately placed bilaterally into extraction sockets of maxillary first molars. Animals were sacrificed after 14 and 28 days of healing, and en bloc specimens were harvested for histological and histomorphometric analysis. Osseointegration was quantified by measuring the percentage of bone-to-implant contact. RESULTS: Bone-to-implant contact (BIC) (mean ± SD) values of moderately rough and turned implants at day 14 in test group were 17.62 ± 6.68 and 10.69 ± 1.48, respectively, while in the control group, they were 46.36 ± 5.08 and 33.29 ± 8.89, respectively. At day 28, BIC values of moderately rough and turned implants in the test group were 25.94 ± 7.87 and 7.83 ± 4.30, respectively, while in the control group, they were 72.99 ± 6.60 and 47.62 ± 18.19, respectively. Statistically significant higher BIC values were measured on moderately rough implants compared to turned implants at 28 days, and the control group compared to the test group for both implant surfaces. Histological observations for the control and the test groups demonstrated initial bone formation around moderately rough implants not only on the surface of the parent bone, as was the case with the turned surfaced implants, but also along the implant surface itself. CONCLUSIONS: Systemic zoledronate administration negatively influences osseointegration. Osseointegration was enhanced adjacent to moderately rough compared to turned implants in both the presence and absence of systemic zoledronate administration. Therefore, topographical surface modification may partially offset the negative impact of zoledronate administration.

The prevalence and risk factors associated with osteoradionecrosis of the jaw in oral and oropharyngeal cancer patients treated with intensity-modulated radiation therapy (IMRT): The Memorial Sloan Kettering Cancer Center experience.

OBJECTIVE: To determine the prevalence and correlation of various risk factors [radiation dose, periodontal status, alcohol and smoking] to the development of osteoradionecrosis (ORN). PATIENTS AND METHODS: The records of 1023 patients treated with IMRT for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) between 2004 and 2013 were retrospectively reviewed to identify patients who developed ORN. Fisher exact tests were used to analyze patient characteristics between ORN patients with OCC and OPC. Paired Wilcoxon tests were used to compare the dose volumes to the ORN and contralateral non-ORN sites. To evaluate an association between ORN and risk factors, a case-control comparison was performed. One to 2 ORN-free patients were selected to match each ORN patient by gender, tumor site and size. General estimation equations models were used to compare the risk factors in ORN cases and matched controls. RESULTS: 44 (4.3%) patients developed ORN during a median follow-up time of 52.5months. In 82% of patients, ORN occurred spontaneously. Patients with OPC are prone to develop ORN earlier compared to patients with OCC (P=0.03). OPC patients received a higher Dmax compared to OCC patients (P=0.01). In the matched case-control analysis the significant risk factors on univariate analysis were poor periodontal status, history of alcohol use and radiation dose (P=0.03, 0.002 and 0.009, respectively) and on multivariate analysis were alcohol use and radiation dose (P=0.004 and 0.026, respectively). CONCLUSION: In our study, higher radiation dose, poor periodontal status and alcohol use are significantly related to the risk of developing ORN.

SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation.

SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared by all subtypes, such as SPRY1, and other lineage-specific super-enhancers, such as SOX2 in brain-derived rhabdoid tumors. Taken together, our findings identify a new chromatin-based epigenetic mechanism underlying the tumor-suppressive activity of SMARCB1.

The influence of titanium surface characteristics on macrophage phenotype polarization during osseous healing in type I diabetic rats: a pilot study.

OBJECTIVES: This study assessed the effect of titanium surface modification on macrophage phenotype polarization and osseous healing under diabetic conditions. MATERIALS AND METHODS: Critical-sized calvarial defects were created in healthy and streptozotocin-induced type I diabetic Sprague-Dawley rats. Titanium (Ti) discs with either large-grit sandblasted and acid-etched micro-rough (SLA) or hydrophilic-modified SLA (modSLA) surfaces were used to cover the healing defect for a period of up to 28 days. Samples of the exudate within the calvarial defect and beneath the titanium discs were collected 1, 4 and 7 days post-surgery for inflammatory cytokine analysis using an ELISA. The macrophage phenotype(s) on the Ti disc surfaces were determined by CD11c+ (M1) and CD163+ (M2) immunofluorescent staining. Samples of the healing defects at days 14 and 28 were also prepared for histomorphometric analysis. RESULTS: Cytokine levels in the diabetic animals were higher than those of the healthy group throughout the observation period. The modSLA surface significantly reduced MIP-2 levels at day 1 in both diabetic and healthy animals, and MCP-1 levels at day 4 in the diabetic animals. Immuno-fluorescent staining showed that an M2-like macrophage phenotype was more frequently found on the modSLA surface at day 1 in healthy and day 4 in both healthy and diabetic animals. Histomorphometric analysis showed more new bone formation on the modSLA surface at days 14 and 28 in both groups, although statistically significant differences were only found in the healthy group. CONCLUSION: Diabetic conditions greatly increased the expression of proinflammatory cytokines during osseous healing. The modSLA surface was shown to promote an M2-like macrophage phenotypic response in titanium adherent macrophages despite the significantly elevated inflammatory environment induced by uncontrolled type I diabetes. Modulation of the macrophage phenotype by the modSLA surface in the early healing period was associated with osseous healing under both healthy and uncontrolled diabetic conditions.

Evaluation and Documentation of Supplemental Oxygen Requirements is Rarely Performed in Patients Hospitalized With COPD.

Rationale: Patients hospitalized with chronic obstructive pulmonary disease (COPD) who require supplemental oxygen (O2) are at increased risk of hospital readmissions. There is a paucity of information regarding quality of evaluation and documentation regarding the need for supplemental O2 in this population.  Objective: To determine the extent to which evaluation and documentation regarding the need for supplemental O2 occurs prior to hospital discharge in patients with COPD.  Methods: We conducted a two-center retrospective cohort study of hospitalized adults with a physician diagnosis of COPD.  We reviewed electronic health records to ascertain whether patients underwent evaluation beyond rest oximetry documenting hypoxemia and if there was adequate documentation of supplemental O2 requirements prior to discharge. Results:  Of 526 patients hospitalized with a primary or secondary discharge diagnosis of COPD, 335 patients (mean age 69 years, 78% with diagnosis of COPD exacerbation) met eligibility criteria. Overall, 1 in 5 (22%, 73/335) hospitalized patients with COPD had an evaluation beyond rest oximetry for supplemental O2 requirements during admission.  Adequate documentation of supplemental O2 requirements occurred in even fewer patients (16%, 54/335). Both evaluation (26% versus 5%, p=0.002) and documentation (19% versus 4%, p=0.001) of supplemental O2 requirements were more common in patients hospitalized for a COPD exacerbation compared to those hospitalized with COPD but without an exacerbation. Conclusions: Evaluation and documentation of supplemental O2 requirements beyond rest oximetry occur infrequently in patients hospitalized with COPD.

Evaluation of the first maxillary molar post-extraction socket as a model for dental implant osseointegration research.

OBJECTIVES: Published information regarding the use of rat jawbones for dental implant osseointegration research is limited and often inconsistent. This study assessed the suitability and feasibility of placing dental implants into the rat maxilla and to establish parameters to be used for dental implant research using this model. MATERIALS AND METHODS: Forty-two customized titanium implants (2 × 3 mm) were placed bilaterally in the maxillary first molar area of 21 Sprague-Dawley rats. Every animal received two implants. The animals were subsequently sacrificed at days 3, 7, 14, 28 and 56 post-surgery. Resin-embedded sections of the implant and surrounding maxilla were prepared for histological and histomorphometric analyses. RESULTS: The mesial root of the first molar in the rat maxilla was the optimal site to place the implant. Although the most apical 2-3 threads of the implant penetrated into the sinus cavity, 2 mm of the remaining implant was embedded in the bone. New bone formation at day 7 around the implant increased further at day 14, as measured by the percentage of bone-to-implant contact (%BIC) and new bone area (%BA) in the implant thread chambers (55.1 ± 8.9% and 63.7 ± 7.7%, respectively). There was a further significant increase between day 14 and 28 (P < 0.05), however, no significant differences were found between day 28 and 56 in either %BIC or %BA. CONCLUSIONS: The mesial root socket of the first molar in the rat maxilla is a useful model for dental implant research. Osseointegration following implant placement as measured by BIC plateaued after 28 days. The recommended implant dimensions are 1.5 mm in diameter and 2 mm in length.