Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

Female sexual function evaluation and intraoperative vaginal reconstruction in bladder cancer.

RC significantly negatively impacts sexual function (SF) in both men and women. While significant research resources have been allocated to examine the deleterious effects of post prostatectomy erectile dysfunction, little attention has been directed towards female sexual function and organ preservation post cystectomy. These academic shortcomings often result in poor provider awareness and inadequate preoperative assessment. As such, it is crucial for all providers involved in female RC care to understand the necessary and available tools for preoperative evaluation, in addition to the anatomic and reconstructive techniques. This review aims to summarize the current preoperative evaluation and available tools of SF assessment and describe in detail the varying operative techniques in the preservation or restoration of SF in women after RC. The review explores the intricacies of preoperative evaluation tools, and intraoperative techniques for organ- and nerve-sparing during radical cystectomy in females. Particular emphasis on vaginal reconstruction after partial or complete resection is provided, including split-thickness skin (STF) graft vaginoplasy, pedicled flaps, myocutaneous flaps and use of bowel segments. In conclusion, this narrative review highlights the importance of understanding anatomic considerations and nerve-sparing strategies in promoting postoperative SF and quality of life. Furthermore, the review describes the advantages and limitations of each organ- and nerve-sparing technique and their impact on sexual function and overall well-being.

Review of Robotic-Assisted Radical Nephrectomy with Inferior Vena Cava Thrombectomy in Renal Cell Carcinoma.

PURPOSE OF REVIEW: Recent advances in minimally invasive technology have compelled surgeons to perform nephrectomy with inferior vena cava thrombectomy using robotic assistance. Here, we aim to review the data comparing open versus robot-assisted nephrectomy with IVC thrombectomy, as well as review operative robotic techniques for nephrectomy with IVC thrombectomy. RECENT FINDINGS: Over the last decade, there have been increasing reports of successful robotic-assisted IVC thrombectomy among skilled robotic surgeons, with case series detailing operative technique, as well as operative and oncologic outcomes for levels I-IV caval thrombus. While there is immense promise in the future of robotic-assisted IVC thrombectomy, further studies with direct comparison to open surgical intervention will be needed to ensure the oncologic principles and outcomes are non-inferior.

Effect of Drop-Piece High-Velocity, Low-Amplitude Manipulation to the Midfoot of Asymptomatic Adult Sprinters on Performance During a Unilateral Horizontal Drop-Jump Test: A Feasibility Investigation.

OBJECTIVE: The purpose of this study was to investigate the feasibility of measuring the immediate effects of drop-piece high-velocity, low-amplitude (DP-HVLA) manipulation to the midfoot region on jump distance in competitive adult sprinters during a standardized unilateral horizontal drop-jump (U-HDJ) test. METHODS: Seven asymptomatic competitive adult sprinters (4 women) were recruited for this study. Testing was conducted on the dominant leg. Participants completed a 10-minute self-selected warm-up, followed by a 6-jump familiarization period with the U-HDJ test. All participants completed 3 U-HDJ trials before and after receiving DP-HVLA chiropractic manipulation to the joints of the midfoot assessed as being hypomobile by a licensed sports chiropractor. The primary outcome of the U-HDJ test was horizontal displacement, measured using an optoelectronic motion-capture system. Mean, SD, and 95% confidence intervals were determined for the posttreatment change in jump distance. A single-sample t test with α = 0.05 assessed the posttreatment change in jumping distance. RESULTS: We were able to measure immediate effects. The preliminary findings showed an increase in jump distance after DP-HVLA manipulation to the midfoot region (mean = 0.06 m, SD = 0.05 m; P = .014; 95% confidence interval, 0.02-0.11; effect size = 1.30). CONCLUSION: This study demonstrates that it was feasible to measure immediate improvement in performance after DP-HVLA chiropractic manipulation in a clinical assessment with correlation to sprinting performance in a population of elite sprinters. As this was a feasibility study, the small sample size, overlapping confidence intervals, and specific niche population limit the extrapolation of these findings.

A putative lysophosphatidylinositol receptor GPR55 modulates hippocampal synaptic plasticity.

GPR55, an orphan G-protein coupled receptor, is activated by lysophosphatidylinositol (LPI) and the endocannabinoid anandamide, as well as by other compounds including THC. LPI is a potent endogenous ligand of GPR55 and neither GPR55 nor LPIs' functions in the brain are well understood. While endocannabinoids are well known to modulate brain synaptic plasticity, the potential role LPI could have on brain plasticity has never been demonstrated. Therefore, we examined not only GPR55 expression, but also the role its endogenous ligand could play in long-term potentiation, a common form of synaptic plasticity. Using quantitative RT-PCR, electrophysiology, and behavioral assays, we examined hippocampal GPR55 expression and function. qRT-PCR results indicate that GPR55 is expressed in hippocampi of both rats and mice. Immunohistochemistry and single cell PCR demonstrates GPR55 protein in pyramidal cells of CA1 and CA3 layers in the hippocampus. Application of the GPR55 endogenous agonist LPI to hippocampal slices of GPR55+/+ mice significantly enhanced CA1 LTP. This effect was absent in GPR55-/- mice, and blocked by the GPR55 antagonist CID 16020046. We also examined paired-pulse ratios of GPR55-/- and GPR55+/+ mice with or without LPI and noted significant enhancement in paired-pulse ratios by LPI in GPR55+/+ mice. Behaviorally, GPR55-/- and GPR55+/+ mice did not differ in memory tasks including novel object recognition, radial arm maze, or Morris water maze. However, performance on radial arm maze and elevated plus maze task suggests GPR55-/- mice have a higher frequency of immobile behavior. This is the first demonstration of LPI involvement in hippocampal synaptic plasticity.

Procedure Selection and Patient Positioning Influence Spine Kinematics During High-Velocity, Low-Amplitude Spinal Manipulation Applied to the Low Back.

OBJECTIVES: This investigation compared indirect 3-dimensional angular kinematics (position, velocity, and acceleration) of the lumbar spine for 2 different high-velocity, low-amplitude (HVLA) spinal manipulation procedures (lumbar spinous pull or push), and altered initial patient lower limb posture. METHODS: Twenty-four participants underwent 6 HVLA procedures directed toward the presumed L4 vertebra, reflecting each combination of 2 variants of a spinal manipulation application technique (spinous pull and push) and 3 initial hip flexion angles (0°, 45°, and 90°) applied using a right lateral recumbent patient position. All contact forces and moments between the patient and the external environment, as well as 3-dimensional kinematics of the patient's pelvis and thorax, were recorded. Lumbar spine angular positions, velocities, and accelerations were analyzed within the preload and impulse stages of each HVLA trial. RESULTS: Lumbar spine left axial rotation was greater for the pull HVLA. The pull HVLA also generated a greater maximum (leftward) and lower minimum (rightward) axial rotation velocity and deceleration and greater leftward and rightward lateral bend velocities, acceleration, and deceleration components. Not flexing the hip produced the greatest amount of extension, as well as the lowest axial rotation and maximum axial rotation acceleration during the impulse. CONCLUSIONS: This investigation provides basic kinematic information for clinicians to understand the similarities and differences between 2 HVLA side-lying manipulations in the lumbar spine. Use of these findings and novel technology can drive future research initiatives that can both affect clinical decision making and influence teaching environments surrounding spinal manipulative therapy skill acquisition.

The Phenomenon of "Therapeutic" Nodal Yield at Cystectomy for Bladder Cancer: Do Not Discount the Will Rogers Effect.

While multiple mechanisms have been hypothesized to explain the therapeutic effect of lymph node (LN) yield in patients with urothelial cell carcinoma (UCC) undergoing radical cystectomy (RC), the effect of stage migration, commonly known as the Will Rogers effect, is often discounted. We reviewed the National Cancer Database for patients with UCC undergoing RC with pathologically node-negative (pN0) disease from 2004 to 2016. We tested for an adjusted association between LN yield and overall survival using multivariable Cox proportional-hazard models. Median survival was estimated using the Kaplan-Meier method. We identified 19 939 patients with pN0 UCC treated with RC. After adjustment, patients in the highest quantile for LN yield (≥26 LNs) had a 34% lower risk of death in comparison to patients in the lowest quantile (≤5 LNs). As we increased the threshold for LN yield for dichotomization from >5 to >15 to >25 LNs, median survival increased from 83 to 95 to 103 mo. The pN0 group with higher LN yield appeared to live longer in this analysis owing to the mathematical artifact of how patients are indexed. Resection of a greater number of negative LNs will lead to higher fidelity for pN0 cohorts being evaluated, as the likelihood of contamination by pN+ cases that were missed will be lower. Patient summary: A strategy to dissect a high number of lymph nodes in patients undergoing removal of their bladder for bladder cancer can be associated with side effects, and the benefit in terms of cancer control or survival remains uncertain. Urologists and their patients should engage in shared decision-making and consider the risks and benefits of more extensive lymph node dissection during surgery.

Sequential intravesical gemcitabine-docetaxel vs. bacillus Calmette-Guerin (BCG) in the treatment of non-muscle invasive bladder cancer: A preliminary cost-effectiveness analysis.

INTRODUCTION: Treatment naïve patients with high-risk non-muscle invasive bladder cancer (NMIBC) are treated with bacillus Calmette-Guérin (BCG) therapy as the standard of care. Recently, intravesical sequential gemcitabine-docetaxel in the BCG-naïve setting was shown to be well-tolerated and effective, raising the possibility of a new first line intravesical therapy. Cost effectiveness of this intervention remains unknown; therefore, we designed a cost effectiveness study evaluating BCG vs. sequential gemcitabine-docetaxel in patients with high risk NMIBC. METHODS: Using TreeAgePro 2019 software, we developed a Markov model to evaluate BCG vs. gemcitabine-docetaxel from the U.S. Medicare perspective with a 2-year time horizon. Model probabilities and utilities were derived from published literature. Direct costs were obtained from Medicare cost databases. Our primary outcomes were effectiveness (measured in quality adjusted life years [QALYs]), cost and the incremental cost-effectiveness ratio with a willingness to pay threshold of $100,000. RESULTS: Our results indicate that while both treatments resulted in similar QALYs of 1.76, the mean costs per patient at 2 years were $12,363 and $7,090 for BCG and gemcitabine-docetaxel, respectively. Therefore, the BCG strategy was dominated by the gemcitabine-docetaxel strategy as it was equally effective and less costly. One way sensitivity analyses were completed and gemcitabine-docetaxel remained a cost-effective strategy. CONCLUSIONS: The findings of this preliminary cost-effectiveness analysis are novel in that they highlight a well tolerated, efficacious drug that is less expensive than the traditional gold standard therapy. In modern medicine, we are more often challenged by agents with marginally increased efficacy but at significantly higher costs; gemcitabine-docetaxel represents a rare entity which is a success for both patients and healthcare systems alike.

Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.

BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome. OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles. RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis. PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.

Splenosis in patient undergoing robotic assisted laparoscopic radical prostatectomy.

Splenosis is a benign condition that is often found in patients with a history of trauma. Most cases are intra-abdominal due to direct seeding of surrounding structures. We report a case of splenosis in the pelvis found in a 59-year-old male during a robotic prostatectomy.

Associations Between Smoking Abstinence, Inhibitory Control, and Smoking Behavior: An fMRI Study.

Nicotine addiction is associated with dysregulated inhibitory control (IC), mediated by corticothalamic circuitry including the right inferior frontal gyrus (rIFG). Among sated smokers, worse IC task performance and greater IC-related rIFG activity have been shown to be associated with greater relapse vulnerability. The present study investigated the effects of smoking abstinence on associations between IC task performance, rIFG activation, and smoking behavior. Smokers (N = 26, 15 female) completed an IC task (Go/Go/No-go) during fMRI scanning followed by a laboratory-based smoking relapse analog task (SRT) on two visits: once when sated and once following 24 h of smoking abstinence. During the SRT, smokers were provided with monetary rewards for incrementally delaying smoking. A significant main effect of No-go accuracy on latency to smoke during the SRT was observed when collapsing across smoking states (abstinent vs. sated). Similarly, a significant main effect of IC-related activation in rIFG on SRT performance was observed across states. The main effect of state, however, was non-significant in both of these models. Furthermore, the interaction between smoking state and No-go accuracy on SRT performance was non-significant, indicating a similar relationship between IC and lapse vulnerability under both sated and abstinent conditions. The state X rIFG activation interaction on SRT performance was likewise non-significant. Post-hoc whole brain analyses indicated that abstinence resulted in greater IC-related activity in the right middle frontal gyrus (MFG) and insula. Activation during IC in these regions was significantly associated with decreased No-go accuracy. Moreover, greater abstinence induced activity in right MFG during IC was associated with smoking sooner on the SRT. These findings are bolstered by the extant literature on the effects of nicotine on executive function and also contribute novel insights on how individual differences in behavioral and neuroimaging measures of IC may influence relapse propensity independent of smoking state.

Symptomatic os trigonum in national level javelin thrower: a case report.

INTRODUCTION: Os trigonum syndrome is a relatively uncommon condition, resulting from compression of a congenital bony anomaly (os trigonum) and adjacent soft tissues during repetitive hyper-plantarflexion. This condition is currently well-described in ballet, soccer, and running athletes, but few cases exist describing os trigonum syndrome in overhead athletes. CASE PRESENTATION: A 22-year-old national level male javelin athlete presented with a recalcitrant history of posterior ankle pain following a hyper-plantarflexion mechanism. Imaging demonstrated a symptomatic os trigonum and inflammation of surrounding soft tissues. Re-aggravation following a conservative trial of care led to orthopaedic referral. Surgical excision of the os trigonum was performed with an open posterolateral approach. The athlete returned to competition three months later with no recurrence of symptoms. SUMMARY: This case discusses the clinical presentation, imaging, and management of a symptomatic os trigonum and related pathologies in a javelin thrower.

INTRODUCTION: Le syndrome de l'os trigone est une pathologie relativement peu fréquente causée par la compression d'une anomalie osseuse congénitale (os trigone) et des tissus mous adjacents durant les mouvements répétitifs en hyperflexion plantaire. Cette pathologie touche souvent les danseuses de ballet, les joueurs de soccer et les coureurs. Peu de cas sont enregistrés chez les athlètes pratiquant des sports comportant des mouvements au-dessus de la tête. PRÉSENTATION DU CAS: Un lanceur de javelot de 22 ans se plaignait d'une douleur postérieure de la cheville déclenchée par des mouvements répétitifs en hyperflexion plantaire. Les examens par imagerie montraient un os trigone symptomatique et une inflammation des tissus périphériques. Une aggravation après une tentative de traitement conservateur a mené à une demande d'une consultation en orthopédie. L'excision chirurgicale de l'os trigone a été réalisée à ciel ouvert par voie d'abord ouverte postérolatérale. L'athlète e repris la compétition au bout de trois mois; ses symptômes ne sont pas réapparus. RÉSUMÉ: Cette étude de cas présente le tableau clinique, les examens par imagerie et la prise en charge d'un os trigone symptomatique et des pathologies apparentées observés chez un lanceur de javelot.

Visual Attention Affects the Amplitude of the Transcranial Magnetic Stimulation-associated Motor-evoked Potential: A Preliminary Study With Clinical Utility.

BACKGROUND: The transcranial magnetic stimulation (TMS)-elicited motor-evoked potential (MEP) is a valuable measure for clinical evaluations of various neurological disorders and is used to determine resting motor threshold for repetitive TMS dosing. Although MEP amplitude is primarily associated with motor system function, there is evidence that nonmotor factors may also influence amplitude. This experiment tested the hypotheses that manipulation of 2 factors (visual attention, cognitive regulation) in human participants would significantly affect MEP amplitude. METHODS: Blocks of MEPs were recorded from the dominant right hand as participants (N=20) were instructed to shift their visual attention (toward and away from the hand) and cognitively regulate the MEPs (rest, attenuate MEP amplitude, potentiate MEP amplitude) using their thoughts (6 blocks, 20 pulses/block, randomized, 110% resting motor threshold). RESULTS: MEP amplitude was significantly affected by the direction of visual attention; looking away from the hand led to higher amplitudes (P=0.003). The relationship with cognitive regulation was nonsignificant. CONCLUSIONS: The significant effect of visual attention on MEP suggests that this should be a standardized parameter in clinical and research studies. These data underscore the importance of rigorous reporting of methods and use of standardized practices for MEP acquisition and TMS dosing to ensure consistent clinical measurement and treatment.

Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability.

Importance: Tobacco use disorder is associated with dysregulated neurocognitive function in the right inferior frontal gyrus (IFG)-one node in a corticothalamic inhibitory control (IC) network. Objective: To examine associations between IC neural circuitry structure and function and lapse/relapse vulnerability in 2 independent studies of adult smokers. Design, Setting, and Participants: In study 1, treatment-seeking smokers (n = 81) completed an IC task during functional magnetic resonance imaging (fMRI) before making a quit attempt and then were followed up for 10 weeks after their quit date. In study 2, a separate group of smokers (n = 26) performed the same IC task during fMRI, followed by completing a laboratory-based smoking relapse analog task. Study 1 was performed at Duke University Medical Center between 2008 and 2012; study 2 was conducted at the Medical University of South Carolina between 2013 and 2016. Main Outcomes and Measures: Associations between corticothalamic-mediated IC, gray-matter volume, and smoking lapse/relapse. Results: Of the 81 study participants in study 1 (cessation study), 45 were women (56%), with mean (SD) age, 38.4 (10.2) years. In study 1, smoking relapse was associated with less gray-matter volume (F1,74 = 28.32; familywise error P threshold = 0.03), greater IC task-related blood oxygenation level-dependent (BOLD) response in the right IFG (F1,78 = 14.87) and thalamus (F1,78 = 14.97) (P < .05), and weaker corticothalamic task-based functional connectivity (tbFC) (F1,77 = 5.87; P = .02). Of the 26 participants in study 2 (laboratory study), 15 were women (58%), with mean (SD) age, 34.9 (10.3). Similar to study 1, in study 2, greater IC-BOLD response in the right IFG (t23 = -2.49; ß = -0.47; P = .02), and weaker corticothalamic tbFC (t22 = 5.62; ß = 0.79; P < .001) were associated with smoking sooner during the smoking relapse-analog task. In both studies, corticothalamic tbFC mediated the association between IC performance and smoking outcomes. Conclusions and Relevance: In these 2 studies, baseline differences in corticothalamic circuitry function were associated with mediated IC and smoking relapse vulnerability. These findings warrant further examination of interventions for augmenting corticothalamic neurotransmission and enhancing IC during the course of tobacco use disorder treatment.

Early bone anchorage to micro- and nano-topographically complex implant surfaces in hyperglycemia.

UNLABELLED: The aim of this work was to investigate the effect of implant surface design on early bone anchorage in the presence of hyperglycemia. 108 Wistar rats were separated into euglycemic (EG) controls and STZ-treated hyperglycemic (HG) groups, and received bilateral femoral custom rectangular implants of two surface topographies: grit blasted (GB) and grit-blast with a superimposed calcium phosphate nanotopography (GB-DCD). The peri-implant bone was subjected to a tensile disruption test 5, 7, and 9days post-operatively (n=28/time point); the force was measured; and the residual peri-implant bone was observed by scanning electron microscopy (SEM). Disruption forces at 5days were not significantly different from zero for the GB implants (p=0.24) in either metabolic group; but were for GB+DCD implants in both metabolic groups (p<0.001). Contact osteogenesis was greater on GB-DCD than the GB surface. The nano-and micro-surfaced implants showed significantly different disruption forces at all time points (e.g. >15N and <5N respectively at 9days). Such differences were not seen within the GB implants, as all values were very low (<5N). Even in hyperglycemia the GB-DCD surface outperformed the GB surfaces in both metabolic groups. Significantly, SEM of peri-implant bone showed compromised intra-fibrillar collagen mineralization in hyperglycemia, while inter-fibrillar and cement line mineralization remained unaffected. Enhanced bone anchorage to the implant surfaces was observed on the nanotopographically complex surface independent of metabolic group. The compromised intra-fibrillar mineralization observed provides a mechanism by which early bone mineralization is affected in hyperglycemia. STATEMENT OF SIGNIFICANCE: It is generally accepted that the hyperglycemia associated with diabetes mellitus compromises bone quality, although the mechanism by which this occurs is unknown. Uncontrolled hyperglycemia is therefore a contra-indication for bone implant placement. It is also known that nano-topographically complex implant surfaces accelerate early peri-implant healing. In this report we show that, in our experimental model, nano-topographically complex surfaces can mitigate the compromised bone healing seen in hyperglycemia. Importantly, we also provide a mechanistic explanation for compromised bone quality in hyperglycemia. We show that intra-fibrillar collagen mineralization is compromised in hyperglycemia, but that interfibrillar and cement line mineralization, remain unaffected.

An improved mechanical testing method to assess bone-implant anchorage.

Recent advances in material science have led to a substantial increase in the topographical complexity of implant surfaces, both on a micro- and a nano-scale. As such, traditional methods of describing implant surfaces - namely numerical determinants of surface roughness - are inadequate for predicting in vivo performance. Biomechanical testing provides an accurate and comparative platform to analyze the performance of biomaterial surfaces. An improved mechanical testing method to test the anchorage of bone to candidate implant surfaces is presented. The method is applicable to both early and later stages of healing and can be employed for any range of chemically or mechanically modified surfaces - but not smooth surfaces. Custom rectangular implants are placed bilaterally in the distal femora of male Wistar rats and collected with the surrounding bone. Test specimens are prepared and potted using a novel breakaway mold and the disruption test is conducted using a mechanical testing machine. This method allows for alignment of the disruption force exactly perpendicular, or parallel, to the plane of the implant surface, and provides an accurate and reproducible means for isolating an exact peri-implant region for testing.

The significance of calcified fibrocartilage on the cortical endplate of the translational sheep spine model.

To gain an understanding of the vertebral cortical endplate and factors that may affect the ability to achieve skeletal attachment to intervertebral implants and fusion, this study aimed to characterize the hypermineralized tissue on the cortical endplate of the vertebral body on a commonly used animal model. Skeletally mature sheep were injected with tetracycline prior to euthanasia and the C2-C3, T5-T6, and L2-L3 spinal motion segments were excised and prepared. Vertebral tissues were imaged using backscatter electron (BSE) imaging, histology, and tetracycline labeling was used to assess bone remodeling within different tissue layers. It was determined that the hypermineralized tissue layer was calcified fibrocartilage (CFC). No tetracycline labels were identified in the CFC layer, in contrast to single and double labels that were present in the underlying bone, indicating the CFC present on the cortical endplate was not being actively remodeled. The average thickness of the CFC layer was 146.3 ± 70.53 µm in the cervical region, 98.2 ± 40.29 µm in the thoracic region, and 150.89 ± 69.25 µm in the lumbar region. This difference in thickness may be attributed to the regional biomechanical properties of the spine. Results from this investigation indicate the presence of a nonremodeling tissue on the cortical endplate of the vertebral body in sheep spines, which attaches the intervertebral disc to the vertebrae. This tissue, if not removed, would likely prevent successful bony attachment to an intervertebral device in spinal fusion studies and total disc replacement surgeries.