NCCN Guideline Concordance Improves Survival in Pediatric and Young Adult Rectal Cancer.

BACKGROUND: Although management guidelines in adult rectal cancer are widely studied, no consensus guidelines exist for the management of pediatric and young adult rectal cancer. METHODS: The National Cancer Database (2004-2018) was queried for pediatric (age 0-21) and young adult (age 22-40) patients with rectal cancer. Patients were analyzed for receipt of National Comprehensive Cancer Network (NCCN) guideline-concordant therapy. Impact on survival was evaluated using Cox regression and Kaplan-Meier analysis. RESULTS: 6655 patients (108 pediatric and 6547 young adult patients) with rectal cancer were included. Similar to previously published NCCN quality measures with overall guideline concordance approaching 90 % in adults, 89.6 % of pediatric and 84.6 % of young adult patients were classified as receiving pre-operative guideline-concordant therapy. However, pediatric patients were significantly less likely to receive post-operative guideline-concordant therapy than young adult patients (65.3 % verse 76.7 %, respectively, p = 0.008). Risk of death was significantly lower for pediatric patients who received post-operative guideline-concordant therapy (HR, 0.313; CI, 0.168-0.581; p < 0.001). In young adult patients, risk of death was significantly lower for those who received pre-operative guideline-concordant therapy (HR, 0.376, CI 0.338-0.417, p < 0.001), and post-operative guideline-concordant therapy (HR, 0.456; CI 0.413-0.505; p < 0.001). DISCUSSION: NCCN-based guidelines may reasonably guide peri-operative management decisions and improve survival in pediatric and young adult rectal cancer. Given the rarity of this cancer in young patients, employment of an experienced surgical and oncologic multidisciplinary team, along with discussion and involvement of the patient and family, are keys for balancing risks and benefits to offering the best therapeutic strategy. TYPE OF STUDY: Retrospective. LEVEL OF EVIDENCE: Level III.

3D printed mesoporous bioactive glass, bioglass 45S5, and ß-TCP scaffolds for regenerative medicine: A comparative in vitro study.

BACKGROUND: While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. OBJECTIVE: The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to ß-Tricalcium phosphate (ß-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells in vitro. METHODS: MBG, BG 45S5, and ß-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (µ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). RESULTS: Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in ß-TCP scaffolds compared to BG 45S5 and MBG groups. CONCLUSION: All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.

Decontamination of the Infected Implant Surface: A Scanning Electron Microscope Study.

A number of treatment options have been explored for peri-implantitis. Seven rough-surfaced implants that failed from peri-implantitis were retrieved. Surfaces were treated by different methods: saline, chlorhexidine, citric acid, 35% phosphoric acid etch gel, hydrogen peroxide, implantoplasty, airborne-particle abrasion, laser, and titanium brush. Implants were observed under scanning electron microscopy. Chemical agents failed to remove any biologic debris. Airborne-particle abrasion, laser, and titanium brush removed part of the biologic debris, and implantoplasty showed complete biologic debris removal. In ex vivo failed implants, implantoplasty showed complete disturbance and removal of bacterial biofilm.

Alkaline phosphatase levels of murine pre-osteoblastic cells on anodized and annealed titanium surfaces.

PURPOSE: This study aimed to evaluate the initial adhesion morphology and alkaline phosphatase (ALP) activity of murine pre-osteoblastic MC3T3-E1 cells cultured on anatase/rutile mixed-phase TiO2 thin films with photocatalytical activity with previously confirmed antibacterial properties. MATERIALS AND METHODS: Anatase/rutile mixed-phase TiO2 thin films fabricated by anodization and annealing of cpTi were used to culture MC3T3-E1 cells to evaluate the initial cellular adhesion morphology and ALP activity in vitro. RESULTS: Compared with MC3T3-E1 cells cultured on cpTi substrates and the control group, cells cultured on anatase/rutile mixed-phase TiO2 thin films exhibited similar ALP levels after cell culture day 9. CONCLUSION: Anodizing and annealing processes fabricate multifunctional surfaces on cpTi with improved osteogenic properties for implants.

Implants With and Without Laser-Microtextured Collar: A 10-Year Clinical and Radiographic Comparative Evaluation.

INTRODUCTION: This article reports, after at least 10 years of follow-up, the comparative data of marginal bone loss (MBL) and periimplant soft tissue parameters, around implant with and without laser-microtextured (L) collar surface, previously reported at 3 years of follow-up. MATERIALS AND METHODS: Twenty implants with L collar surface (test) were placed adjacent to 20 control implants with machined (M) collar surface in 15 partially edentulous patients, who were followed up for at least 10 years as part of a prospective longitudinal study. The plaque score, bleeding on probing (BoP) score, and probing depth (PD) were recorded at baseline and at each year follow-up examination. Mucosal recession (MR), and radiographic MBL were assessed at baseline and after at least 10 years. RESULTS: Four patients were lost during follow-up, so the number of implants that have been followed for at least 10 years was 32 (16 tests and 16 controls). At the end of the follow-up period, no significant differences were found between the study groups regarding the presence of plaque and BoP (P > 0.05). A statistically significant difference between test and control implant was found for mean PD (2.3 ± 0.7 mm vs 3.8 ± 0.8), MBL (1.23 ± 0.21 mm vs 2.8 ± 0.9 mm), and mean MR (1.08 ± 0.4 mm vs 2.46 ± 0.3 mm). CONCLUSION: Results suggest that after at least 10 years of function, implants with laser-microtexturing (L) collar surface, compared with implants with machined surface, lead to lower MBL and PD.

Human Histologic Evidence of Reosseointegration Around an Implant Affected with Peri-implantitis Following Decontamination with Sterile Saline and Antiseptics: A Case History Report.

The treatment of peri-implant disease is one of the most controversial topics in implant dentistry. The multifactorial etiology and the myriad proposed techniques for managing the problem make successful decontamination of an implant surface affected by peri-implantitis one of the more unpredictable challenges dental practitioners have to face. This article presents the first known published case report demonstrating human histologic evidence of reosseointegration using a plastic curette for mechanical debridement and dilute sodium hypochlorite, hydrogen peroxide, and sterile saline for chemical detoxification. Guided bone regeneration in the infrabony component of the peri-implantitis lesion was accomplished using calcium sulfate and bovine bone as grafting materials and a porcine collagen barrier for connective tissue and epithelial exclusion.

Bone regeneration in critical bone defects using three-dimensionally printed ß-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2.

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3D) printing technology we have created custom 3D scaffolds of hydroxyapatite (HA)/beta-tri-calcium phosphate (ß-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. Nearly 15% HA:85% ß-TCP scaffolds were designed using Robocad software, fabricated using a 3D Robocasting system, and sintered at 1100°C for 4 h. Scaffolds were coated with BMP-2 (200 ng mL-1 ), dypiridamole 100 µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3 mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. Micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/ß-TCP-dipyridamole and HA/ß-TCP-BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4, and 8 weeks (n = 5 per group; p ≤ 0.05, p ≤ 0.05, and p ≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/ß-TCP- dipyridamole and HA/ß-TCP-BMP-2 scaffolds. Coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/ß-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 366-375, 2017.

Cell Response to Surfaces: A Concise Summary.

Surface nano- and microtexturing techniques have been used to enhance osseointegration, but how these surfaces work is not well understood. Using the knowledge gained from the cell and molecular biology fields, tissue engineering studies, and their own work, the authors and other researchers have developed surfaces for in vitro and in vivo control of the function of cells and tissues. In the present article, the authors summarize what they know about the process of cell response to surfaces, and what they have done and can do to develop surfaces that control hard- and soft-tissue formation and integration of implants. This article is intended to add to the clinician's understanding of cell and surface interactions, explain why certain surfaces are currently used, and describe what surfaces clinicians may see in the future.

Compliance with a New York State 2010 HIV Testing Law: Is There Racial/Ethnic Bias in HIV Testing? Experience of Monroe County, New York, 2012.

BACKGROUND: While routine HIV testing in the general population is a national recommendation, actual practice may vary. PURPOSE: To determine risk factors associated with HIV testing after the adoption of a New York State law in 2010 mandating that health care providers offer HIV testing in all clinical settings. METHODS: Survey data from Monroe County, New York, were collected in 2012 for adults aged 18-64 years and analyzed in 2014. Logistic regression was used to identify risk factors independently associated with HIV testing and high-risk behavior. RESULTS: Among adults aged 18-34, fewer Whites were offered HIV testing in the past year by their doctors compared with Blacks (34% vs 64%) despite having similar rates of any HIV high-risk behavior (20% overall). For adults aged 35-64 years, fewer Whites than Blacks were ever tested for HIV (42% vs 71%), offered HIV testing in past year (17% vs 40%), and reported any HIV high-risk behavior (3% vs 13%). Latinos showed intermediate levels. With logistic regression analysis, ever tested for HIV was independently associated with only race/ethnicity; offered HIV testing in the past year was associated with females, Blacks and Latinos, aged 18-34 years, and having a routine health checkup in past year; any HIV high-risk behavior was associated with only younger age. CONCLUSIONS: To improve HIV testing rates as well as compliance with state laws and national guidelines, targeted efforts should be considered that improve perceptions of risk and emphasize the value of routine HIV screening, including those directed at White adults and their health care providers.

Design and validation of a dynamic cell-culture system for bone biology research and exogenous tissue-engineering applications.

Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd.

Photocatalytical Antibacterial Activity of Mixed-Phase TiO2 Nanocomposite Thin Films against Aggregatibacter actinomycetemcomitans.

Mixed-phase TiO2 nanocomposite thin films consisting of anatase and rutile prepared on commercially pure Ti sheets via the electrochemical anodization and annealing treatments were investigated in terms of their photocatalytic activity for antibacterial use around dental implants. The resulting films were characterized by scanning electron microscopy (SEM), and X-ray diffraction (XRD). The topology was assessed by White Light Optical Profiling (WLOP) in the Vertical Scanning Interferometer (VSI) mode. Representative height descriptive parameters of roughness R a and R z were calculated. The photocatalytic activity of the resulting TiO2 films was evaluated by the photodegradation of Rhodamine B (RhB) dye solution. The antibacterial ability of the photocatalyst was examined by Aggregatibacter actinomycetemcomitans suspensions in a colony-forming assay. XRD showed that anatase/rutile mixed-phase TiO2 thin films were predominantly in anatase and rutile that were 54.6 wt% and 41.9 wt%, respectively. Craters (2-5 µm) and protruding hills (10-50 µm) on Ti substrates were produced after electrochemical anodization with higher R a and R z surface roughness values. Anatase/rutile mixed-phase TiO2 thin films showed 26% photocatalytic decolorization toward RhB dye solution. The number of colonizing bacteria on anatase/rutile mixed-phase TiO2 thin films was decreased significantly in vitro. The photocatalyst was effective against A. actinomycetemcomitans colonization.

Pancreatic retransplantation is associated with poor allograft survival: an update of the United Network for Organ Sharing database.

UNLABELLED: The aim of the study was to assess outcomes of pancreas retransplantation versus primary pancreas transplantation. METHODS: Data from the United Network for Organ Sharing database on all adult (age, ≥18 years) subjects who received pancreas and kidney-pancreas transplants between 1996 and 2012 were analyzed (n = 20,854). The subjects were analyzed in the following 2 groups: retransplant (n = 1149) and primary transplant (n = 19,705). RESULTS: Kaplan-Meier analysis demonstrated significantly different patient survival (P < 0.0001) and death-censored graft survival (P < 0.0001) between the primary transplant versus retransplant subjects. Allograft survival was significantly poorer in the retransplantation group. Patient survival was greater in the retransplant group. CONCLUSIONS: The results of our study differ from previous studies, which showed similar allograft survival in primary and secondary pancreas transplants. Further studies may elucidate specific patients who will benefit from retransplantation. At the present time, it would appear that pancreas retransplantation is associated with poor graft survival and that retransplantation should not be considered for all patients with primary pancreatic allograft failure.

Treatment of a mandibular cyst before implant placement: case report.

The aim of this case study is to present a clinical approach to treatment of a mandibular intrabony cyst employing guided bone regeneration principles and protection of the mandibular nerve prior to implant placement. A treatment approach employing a combination of grafting materials and membranes was used to treat the cyst and protect the mandibular nerve prior to implant placement. Micro CT, as well as histology and histomorphometrics, was used to evaluate treatment outcomes. Histological inspection showed bone regeneration at the grafting site. Histomorphometric analysis of the biopsy core rendered a total bone percent area of 58.87% and 41.13% soft tissue. Out of the total bone percent area, 90.45% was revealed as vital bone and 9.55% was graft remnant. The grafted area is supporting an implant-supported prosthesis in full function.

Antibacterial Activity of As-Annealed TiO2 Nanotubes Doped with Ag Nanoparticles against Periodontal Pathogens.

It is important to develop functional transmucosal implant surfaces that reduce the number of initially adhering bacteria and they need to be modified to improve the anti-bacterial performance. Commercially pure Ti sheets were anodized in an electrolyte containing ethylene glycol, distilled water and ammonium fluoride at room temperature to produce TiO2 nanotubes. These structures were then annealed at 450°C to transform them to anatase. As-annealed TiO2 nanotubes were then treated in an electrolyte containing 80.7 g/L NiSO4 ·7H2O, 41 g/L MgSO4 ·7H2O, 45 g/L H3BO3, and 1.44 g/L Ag2SO4 at 20°C by the application of 9 V AC voltage for doping them with silver. As-annealed TiO2 nanotubes and as-annealed Ag doped TiO2 nanotubes were evaluated by SEM, FESEM, and XRD. Antibacterial activity was assessed by determining the adherence of A. actinomycetemcomitans, T. forsythia, and C. rectus to the surface of the nanotubes. Bacterial morphology was examined using an SEM. As-annealed Ag doped TiO2 nanotubes revealed intense peak of Ag. Bacterial death against the as-annealed Ag doped TiO2 nanotubes were detected against A. actinomycetemcomitans, T. forsythia, and C. rectus indicating antibacterial efficacy.

3D conductive nanocomposite scaffold for bone tissue engineering.

Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D) ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene) poly(4-styrene sulfonate) (PEDOT:PSS), in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli.

Meningitis in a School-Aged Child due to Haemophilus influenzae Type E during the Post-Conjugate Vaccine Era-Monroe County, NY, 2011.

In late October 2011, the Monroe County Department of Public Health (MCDPH) was notified of a suspected case of meningitis in a 9-year old girl from Monroe County, NY. Laboratory testing at the New York State Department of Health (NYSDOH) Wadsworth Center confirmed the identification of Haemophilus influenzae serotype e (Hie) isolated from the patient's cerebrospinal fluid (CSF) using real-time polymerase chain reaction (RT-PCR). The universal immunization of infants with conjugate H. influenzae type b (Hib) vaccine has significantly reduced the incidence of invasive Hib disease, including meningitis, one of the most serious complications for infected children. Not surprisingly, as the epidemiology of invasive H. influenzae continues to change, non-Hib serotypes will likely become more common. The findings reported here underscore the importance for clinicians, public health officials, and laboratory staff to consider non-Hib pathogens in pediatric cases of meningitis, especially when initial investigations are inconclusive.

Development of a guided bone regeneration device using salicylic acid-poly(anhydride-ester) polymers and osteoconductive scaffolds.

Successful repair of craniofacial and periodontal tissue defects ideally involves a combined therapy that includes inflammation modulation, control of soft tissue infiltration, and bone regeneration. In this study, an anti-inflammatory polymer, salicylic acid-based poly(anhydride-ester) (SAPAE) and a three-dimensional osteoconductive ceramic scaffold were evaluated as a combined guided bone regeneration (GBR) system for concurrent control of inflammation, soft tissue ingrowth, and bone repair in a rabbit cranial defect model. At time periods of 1, 3, and 8 weeks, five groups were compared: (1) scaffolds with a solid ceramic cap (as a GBR structure); (2) scaffolds with no cap; (3) scaffolds with a poly(lactide-glycolide) cap; (4) scaffolds with a slow release SAPAE polymer cap; and (5) scaffolds with a fast release SAPAE polymer cap. Cellular infiltration and bone formation in these scaffolds were evaluated to assess inflammation and bone repair capacity of the test groups. The SAPAE polymers suppressed inflammation and displayed no deleterious effect on bone formation. Additional work is warranted to optimize the anti-inflammatory action of the SAPAE, GBR suppression of soft tissue infiltration, and stimulation of bone formation in the scaffolds and create a composite device for successful repair of craniofacial and periodontal tissue defects.

Why we cannot grow a human arm.

There are several significant issues that prevent us from growing a human arm now, or within the next 10-20 years. From a tissue engineering perspective, while we can grow many of the components necessary for construction of a human arm, we can only grow them in relatively small volumes, and when scaled up to large volumes we lack the ability to develop adequate blood/nerve supply. From a genetic engineering perspective, we will probably never be able to turn on the specific genes necessary to "grow an arm" unless it is attached to a fetus and this presents enormous ethical issues related to farming of human organs and structures. Perhaps the most daunting problem facing the transplantation of a tissue engineered or transplanted arm is that of re-innervation of the structure. Since the sensory and motor nerve cells of the arm are located outside of the structure, re-innervation requires those nerves to regenerate over relatively large distances to repopulate the nervous system of the arm. This is something with which we have had little success. We can grow repair parts, but "growing an arm" presents too many insurmountable problems. The best we could possibly do with tissue engineering or genetic engineering would be the equivalent of a fetal arm and the technical problems, costs, and ethical hurdles are enormous. A more likely solution is a functional, permanent, neuroelectronically-controlled prosthesis. These are nearly a reality today.

Analysis of dimensional changes in the screw and the surface topography at the interface of a titanium screw and a zirconia abutment under cyclic loading: an in vitro study.

PURPOSE: The purpose of this experiment was to analyze the mechanics of the ceramic abutment-implant joint and the dimensional changes in the abutment screws from cyclic loading. MATERIALS AND METHODS: Two groups of experimental assemblies were used, one with zirconia abutments and the other with titanium abutments (n = 10). Each specimen consisted of an implant, an abutment, and a metal crown affixed in an acrylic resin base. The specimens were subjected to cyclic loading of 200 N for 1 million cycles at 10 Hz. After loading, a torque-angle signature analysis was done, the dimensions of the screws were measured, and the implant-abutment interfaces were examined with scanning electron microscopy. RESULTS: There was a statistically significant increase in the total length of the screws: 121 µm in the titanium group versus 88 µm in the zirconia group (P < .004). Microscopic analysis showed collected debris on the zirconia abutment undersurface and the screws. A statistically similar decrease in torque was observed: 18% for zirconia versus 13.5% for titanium. Radiographic microanalysis revealed that the debris collected in the zirconia assemblies was essentially a collection of titanium, vanadium, and aluminum, with traces of zirconium. CONCLUSIONS: While there was a loss of torque in both types of abutments, the stability of the zirconia abutment-implant joint was not affected by the loading. The study provides a better understanding of zirconia abutments, screw designs, and the mechanism holding together the implant-abutment assembly.