Higher working memory predicts slower functional decline in autopsy-confirmed Alzheimer's disease.

BACKGROUND: There is heterogeneity in the pattern of early cognitive deficits in Alzheimer's disease (AD). However, whether the severity of initial cognitive deficits relates to different clinical trajectories of AD progression is unclear. OBJECTIVE: To determine if deficits in specific cognitive domains at the initial visit relate to the rate of progression in clinical trajectories of AD dementia. METHODS: 68 subjects from the National Alzheimer's Coordinating Center database who had autopsy-confirmed AD as the primary diagnosis and at least 3 serial assessments a year apart, with a Mini-Mental State Examination (MMSE) score >15 and a Clinical Dementia Rating Scale-Global (CDR-G) score ≤1 at the initial visit were included. A mixed regression model was used to examine the association between initial neuropsychological performance and rate of change on the MMSE and CDR Sum of Boxes. RESULTS: Preservation of working memory, but not episodic memory, in the mild cognitive impairment and early dementia stages of AD relates to slower rate of functional decline. DISCUSSION: These findings are relevant for estimating the rate of decline in AD clinical trials and in counseling patients and families. Improving working memory performance as a possible avenue to decrease the rate of functional decline in AD dementia warrants closer investigation.

The Effect of Intensive Education On Urinary Incontinence Following Radical Prostatectomy: A Randomized Control Trial.

Intense bladder control education failed to improve bladder control among patients who underwent a radical prostatectomy as treatment of their prostate cancer. Despite this educational intervention, participants continued to experience post-operative bladder control problems. Nurses need to develop and implement novel interventions that might enhance bladder control.

Prostate cancer patients older than 70 years treated by radical prostatectomy have higher biochemical recurrence rate than their matched younger counterpart.

BACKGROUND: Consensus on prostate cancer (PCA) treatment in older men is currently lacking. We evaluated clinicopathological and oncological outcomes in patients >70-year-old treated with radical prostatectomy (RP). METHODS: Clinicopathological and follow-up (FU) data for >70-year-old RP men (2000-2011) were recorded. Association between preoperative features, extraprostatic extension (EPE) and biochemical failure (bF), and postoperative features and bF, was explored. Patients >70-year-old were matched with younger (50- to 70-year-old) men with similar RP features to analyze the effect of age on bF. RESULTS: Two hundred eighteen RP patients were >70-year-old. Clinical stage (cT) was T1 in 74.1%. Biopsy (Bx) Gleason score (GS) was 6 (35.8%), 7 (45.9%), and ≥8 (18.3%); RP GS was 6 (10.1%), 7 (63.3%), and ≥8 (26.6%). Median PSAD was 0.14 (range: 0.01-1.12). Pathologic stage (pT) was pT3 in 45.9%. bF occurred in 14.0%. Best preoperative predictive model for pT3 disease included D'Amico risk, number of Bx positive cores, PSAD, maximum % of PCA per core (P < 0.0001); cT, PSAD and primary Bx Gleason pattern best predicted bF preoperatively (P = 0.0031). Among postoperative features, high RP GS, positive margins, and pT3 were significantly associated with bF. Margin status and pT best predicted bF. Patients >70-year-old had 85% higher odds of bF compared to younger men (P = 0.036). CONCLUSIONS: PCA detected in >70-year-old men shows adverse pathologic features. Failure rate is significantly higher in older than in matched younger patients.

PINOT NOIR: pulmonic insufficiency improvement with nitric oxide inhalational response.

BACKGROUND: Tetralogy of Fallot (TOF) repair and pulmonary valvotomy for pulmonary stenosis (PS) lead to progressive pulmonary insufficiency (PI), right ventricular enlargement and dysfunction. This study assessed whether pulmonary regurgitant fraction measured by cardiovascular magnetic resonance (CMR) could be reduced with inhaled nitric oxide (iNO). METHODS: Patients with at least moderate PI by echocardiography undergoing clinically indicated CMR were prospectively enrolled. Patients with residual hemodynamic lesions were excluded. Ventricular volume and blood flow sequences were obtained at baseline and during administration of 40 ppm iNO. RESULTS: Sixteen patients (11 with repaired TOF and 5 with repaired PS) completed the protocol with adequate data for analysis. The median age [range] was 35 [19-46] years, BMI was 26 ± 5 kg/m(2) (mean ± SD), 50% were women and 75% were in NYHA class I. Right ventricular end diastolic volume index for the cohort was 157 ± 33 mL/m(2), end systolic volume index was 93 ± 20 mL/m(2) and right ventricular ejection fraction was 40 ± 6%. Baseline pulmonary regurgitant volume was 45 ± 25 mL/beat and regurgitant fraction was 35 ± 16%. During administration of iNO, regurgitant volume was reduced by an average of 6 ± 9% (p=0.01) and regurgitant fraction was reduced by an average of 5 ± 8% (p=0.02). No significant changes were observed in ventricular indices for either the left or right ventricle. CONCLUSION: iNO was successfully administered during CMR acquisition and appears to reduce regurgitant fraction in patients with at least moderate PI suggesting a potential role for selective pulmonary vasodilator therapy in these patients. TRIALS REGISTRATION: ClinicalTrials.gov, NCT00543933.

Effect of pretension and suture needle type on mechanical properties of acellular human dermis patches for rotator cuff repair.

BACKGROUND: Dermal grafts are used for rotator cuff repair and augmentation. Although the in vitro biomechanical properties of dermal grafts have been reported previously, clinical questions related to their biomechanical performance as a surgical construct and the effect of surgical variables that could potentially improve repair outcomes have not been studied. METHODS: This study evaluated the failure and fatigue biomechanics of acellular dermis constructs tested in a clinically relevant size (4 × 4 cm patches) and manner (loaded via sutures) for rotator cuff repair. Also investigated were the effect of 2 surgical variables: (1) the fixation of grafts under varying magnitudes of pretension (0, 10, 20N), and (2) the use of reverse-cutting vs tapered needles for suturing grafts. RESULTS: Dermis constructs stretched ∼25% before bearing significant loads in the high stiffness region. Although 91% of the patches withstood 2500 cycles of loading to 150 N, the constructs stretched 13 to 19 mm after fatigue loading. This elongation could be reduced by 20% to 32% when reverse-cutting needles were used to prepare constructs or by applying 20 N of in situ circumferential pretension to the constructs before loading. CONCLUSIONS: Although dermis patches demonstrated robustness for use in rotator cuff repair, the patches underwent significant, substantial, and presumably nonrecoverable elongation, even at low physiologic loads. This study indicates that use of reverse-cutting needles for suture passage, preconditioning (cyclically stretching several times), and/or surgical fixation under at least 20 N of circumferential pretension could be developed as strategies to reduce compliance of dermis for its use for rotator cuff repair.

Reinforced fascia patch limits cyclic gapping of rotator cuff repairs in a human cadaveric model.

BACKGROUND: Scaffolds continue to be developed and used for rotator cuff repair augmentation, but clinical or biomechanical data to inform their use are limited. We have developed a reinforced fascia lata patch with mechanical properties to meet the needs of musculoskeletal applications. The objective of this study was to assess the extent to which augmentation of a primary human rotator cuff repair with the reinforced fascia patch can reduce gap formation during in vitro cyclic loading. MATERIALS AND METHODS: Nine paired human cadaveric shoulders were used to investigate the cyclic gap formation and failure properties of augmented and non-augmented rotator cuff repairs with loading of 5 to 180 N for 1000 cycles. RESULTS: Augmentation significantly decreased the amount of gap formation at cycles 1, 10, 100, and 1000 compared with non-augmented repairs (P < .01). The mean gap formation of the augmented repairs was 1.8 mm after the first cycle of pull (vs 3.6 mm for non-augmented repairs) and remained less than 5 mm after 1000 cycles of loading (4.7 mm for augmented repairs vs 7.3 mm for non-augmented repairs). Furthermore, all augmented repairs were able to complete the 1000-cycle loading protocol, whereas 3 of 9 non-augmented repairs failed before completing 1000 loading cycles. CONCLUSIONS: This study supports further investigation of reinforced fascia patches to provide mechanical augmentation, minimize tendon retraction, and possibly reduce the incidence of rotator cuff repair failure. Future investigation in animal and human studies will be necessary to fully define the efficacy of the reinforced fascia device in a biologic healing environment.

Understanding equivalence and noninferiority testing.

Increasingly, the goal of many studies is to determine if new therapies have equivalent or noninferior efficacies to the ones currently in use. These studies are called equivalence/noninferiority studies, and the statistical methods for their analysis require only simple modifications to the traditional hypotheses testing framework. Nevertheless, important and subtle issues arise with the application of such methods. This article describes the concepts and statistical methods involved in testing equivalence/noninferiority. The aim is to enable the clinician to understand and critically assess the growing number of articles utilizing such methods.

Characterization of and host response to tyramine substituted-hyaluronan enriched fascia extracellular matrix.

Naturally-occurring biomaterial scaffolds derived from extracellular matrix (ECM) have been previously investigated for soft tissue repair. We propose to enrich fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) to modulate inflammation associated with implantation and enhance fibroblast infiltration. As critical determinants of constructive remodeling, the host inflammatory response and macrophage polarization to TS-HA enriched fascia were characterized in a rat abdominal wall model. TS-HA treated fascia with cross-linking had a similar lymphocyte (P = 0.11) and plasma cell (P = 0.13) densities, greater macrophage (P = 0.001) and giant cell (P < 0.0001) densities, and a lower density of fibroblast-like cells (P < 0.0001) than water treated controls. Treated fascia, with or without cross-linking, exhibited a predominantly M2 pro-remodeling macrophage profile similar to water controls (P = 0.82), which is suggestive of constructive tissue remodeling. Our findings demonstrated that HA augmentation can alter the host response to an ECM, but the appropriate concentration and molecular weight needed to minimize chronic inflammation within the scaffold remains to be determined.

Challenges in meta-analysis of randomized clinical trials for rare harmful cardiovascular events: the case of rosiglitazone.

Rare cardiovascular events of commonly used drugs are important to document and investigate, but single trials are notoriously underpowered to provide conclusive evidence. Recently, meta-analyses have been used to improve on the power. A recent rosiglitazone meta-analysis heightened the debate about the usefulness and limitations of meta-analysis in this setting. In this review, we examined the methods used in previous published meta-analyses for harmful cardiovascular events, with special attention to the rosiglitazone meta-analyses, and give suggestions for the improvement of methods and interpretation of such meta-analyses. The conduct of meta-analysis in this context is particularly difficult and requires timely investigation, availability of high-quality data on harms, and statistical expertise. There are important decisions that need to be made about selecting the appropriate analytical methods and performing sensitivity analyses to evaluate whether the results are robust to different analytical choices.

Pathologic characteristics of solitary small renal masses: can they be predicted by preoperative clinical parameters?

We studied the pathologic features and whether clinical features could predict pathologic outcomes in small renal masses. The study included all adult patients with solitary, nonmetastatic renal masses 4 cm or smaller confirmed by nephrectomy or needle biopsy between 2004 and 2006. Tumor size, histologic type, Fuhrman nuclear grade, and stage were obtained from surgical pathology reports. Clinical variables included age, sex, tumor size, and symptomatology. The study included 290 men and 198 women (mean age, 59.3 years). Median tumor size was 2.6 cm (range, 0.5-4.0 cm). Approximately 84% of masses were incidentally detected. Nonneoplastic entities, benign neoplasms, and low- and high-grade carcinoma accounted for 1.6%, 18.0%, 49.0%, and 31.4% of masses, respectively. Women were more likely to have a benign mass (27.3% vs 14.5% of men, P < .001). Age (P = .56), tumor size (mean, 2.63 vs 2.46 cm for benign; P = .08), and symptomatology (P = .46) were not associated with malignancy. Multivariate analyses using sex, age, tumor size, and symptomatology failed to produce a model useful to predict the pathology of individual tumors. This inability may argue for an increased role for needle biopsy in their evaluation.

Meta-analysis: Its strengths and limitations.

Nowadays, doctors face an overwhelming amount of information, even in narrow areas of interest. In response, reviews designed to summarize the large volumes of information are frequently published. When a review is done systematically, following certain criteria, and the results are pooled and analyzed quantitatively, it is called a meta-analysis. A well-designed meta-analysis can provide valuable information for researchers, policymakers, and clinicians. However, there are many critical caveats in performing and interpreting them, and thus many ways in which meta-analyses can yield misleading information.

The Efficiency of Bone Marrow Aspiration for the Harvest of Connective Tissue Progenitors from the Human Iliac Crest.

BACKGROUND: The rational design and optimization of tissue engineering strategies for cell-based therapy requires a baseline understanding of the concentration and prevalence of osteogenic progenitor cell populations in the source tissues. The aim of this study was to (1) define the efficiency of, and variation among individuals in, bone marrow aspiration as a means of osteogenic connective tissue progenitor (CTP-O) harvest compared with harvest from iliac cancellous bone, and (2) determine the location of CTP-Os within native cancellous bone and their distribution between the marrow-space and trabecular-surface tissue compartments. METHODS: Eight 2-mL bone marrow aspiration (BMA) samples and one 7-mm transcortical biopsy sample were obtained from the anterior iliac crest of 33 human subjects. Two cell populations were obtained from the iliac cancellous bone (ICB) sample. The ICB sample was placed into αMEM (alpha-minimal essential medium) with antibiotic-antimycotic and minced into small pieces (1 to 2 mm in diameter) with a sharp osteotome. Cells that could be mechanically disassociated from the ICB sample were defined as marrow-space (IC-MS) cells, and cells that were disassociated only after enzymatic digestion were defined as trabecular-surface (IC-TS) cells. The 3 sources of bone and marrow-derived cells were compared on the basis of cellularity and the concentration and prevalence of CTP-Os through colony-forming unit (CFU) analysis. RESULTS: Large variation was seen among patients with respect to cell and CTP-O yield from the IC-MS, IC-TS, and BMA samples and in the relative distribution of CTP-Os between the IC-MS and IC-TS fractions. The CTP-O prevalence was highest in the IC-TS fraction, which was 11.4-fold greater than in the IC-MS fraction (p < 0.0001) and 1.7-fold greater than in the BMA fraction. However, the median concentration of CTP-Os in the ICB (combining MS and TS fractions) was only 3.04 ± 1.1-fold greater than that in BMA (4,265 compared with 1,402 CTP/mL; p = 0.00004). CONCLUSIONS: Bone marrow aspiration of a 2-mL volume at a given needle site is an effective means of harvesting CTP-Os, albeit diluted with peripheral blood. However, the median concentration of CTP-Os is 3-fold less than from native iliac cancellous bone. The distribution of CTP-Os between the IC-MS and IC-TS fractions varies widely among patients. CLINICAL RELEVANCE: Bone marrow aspiration is an effective means of harvesting CTP-Os but is associated with dilution with peripheral blood. Overall, we found that 63.5% of all CTP-Os within iliac cancellous bone resided on the trabecular surface; however, 48% of the patients had more CTP-Os contributed by the IC-MS than the IC-TS fraction.

Hybrid approaches to thoracic aortic aneurysms: the role of endovascular elephant trunk completion.

BACKGROUND: Thoracic aortic aneurysm affecting the arch and proximal descending thoracic aorta requires 2-stage repairs that include proximal elephant trunk graft placement and completion of thoracic or thoracoabdominal repair. The application of endovascular grafting to complete the proximal procedure avoids a thoracotomy and may improve the morbidity and mortality of the patient population at risk. METHODS AND RESULTS: A retrospective review of 399 thoracic endovascular grafts at our institution between 2000 and 2004 identified 22 patients who required elephant trunk and endovascular completion. Three patients underwent mesenteric bypass in addition to their proximal repairs. Mean follow-up was 10 months (range 1 to 42 months); there were no ruptures, and all patients returned for follow-up. Technical success was achieved in all patients. The 1-, 12-, and 24-month mortality rates (by Kaplan-Meier analysis) were 4.5%, 15.8%, and 15.8%, respectively. Caudal migration of the endograft occurred in 1 patient, and all but 2 aneurysms decreased or remained stable in size. The 2 patients with growth included a type III endoleak (which resolved after treatment) and pressurization through an expanded PTFE stentgraft. Three cases of transient paraparesis occurred (all in patients requiring mesenteric bypass or abdominal aortic aneurysm repair), and there were no paraplegias or strokes. CONCLUSIONS: Endovascular completion of elephant trunks is feasible and can be accomplished with minimal mortality. Meticulous imaging follow-up is required to detect persistent aneurysm pressurization and to verify the integrity of the repair. Improvements in implant design and delivery systems will further simplify the second-stage portion of these complex aneurysm repairs.

Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma.

OBJECTIVE: To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma. PATIENTS AND METHODS: Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Français du Myélome, respectively. RESULTS: Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%). CONCLUSIONS: The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.

The role of race, socioeconomic status, and distance traveled on the outcome of African-American patients with multiple myeloma.

The incidence and mortality of multiple myeloma (MM) in African-Americans is double that in whites. We questioned whether race, socioeconomic status, and distance traveled affect overall survival. In a retrospective review of the records of 292 patients with MM. We found that the median age was 60 years and 38 patients were African-Americans. The mean distance traveled was 67.7 miles. The median overall survival was similar in African-Americans and whites. Race, distance traveled and socioeconomic status were not independent prognostic factors for overall survival. In conclusion, socioeconomic status, distance traveled and race did not affect outcomes of MM patients treated at a specialized myeloma center.

Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial.

BACKGROUND: Single-agent arsenic trioxide has shown promising results in patients with relapsed or refractory multiple myeloma (MM). Because preclinical data suggested greater activity with dexamethasone and ascorbic acid, a phase 2 trial of the combination of arsenic trioxide, dexamethasone, and ascorbic acid in patients with relapsed or refractory MM was conducted. METHODS: Twenty patients in whom no more than two previous therapies had failed were enrolled. The mean age was 62 yr, and 55% of the patients had refractory disease. The regimen consisted of 14- or 15-wk cycles, with the first cycle considered induction, followed by one or two consolidation cycles with a reduced steroid schedule and then a maintenance cycle in responding patients. RESULTS: The overall response rate was 30%, with at least stable disease in 80% of patients. Median progression- free survival was 316 d in all patients and 584 d in those with a response. The regimen was well tolerated, with most adverse events being mild or moderate. CONCLUSIONS: This study showed the clinical efficacy and tolerability of the combination of arsenic trioxide, dexamethasone, and ascorbic acid. Further study is warranted.

In search of fewer independent risk factors.

More than 1100 articles now appear annually investigating "independent risk factors" or "independent predictors" for various clinical outcomes. In medical research, independence is generally defined in a statistical sense: a variable is called an independent risk factor if it has a significant contribution to an outcome in a statistical model that includes established risk factors. As such, independence is based on a specific statistical model and depends on the set of established risk factors included in that model. Even when strong statistical evidence indicates that a variable is an independent risk factor for an outcome, this does not necessarily indicate that the risk factor causally contributes to the outcome. The opposite is also true: risk factors that have causal relationships with the outcome will not necessarily prove to be independent risk factors. These are basic statistical principles that are too often given short shrift in medical research. Herein, we discuss the clinical implications conferred by the above definition of independence, primarily using examples from recent cardiovascular literature. A glossary and schema are provided to help clinicians and researchers understand and discuss these matters effectively.

A Web-Based Mindfulness Stress Management Program in a Corporate Call Center: A Randomized Clinical Trial to Evaluate the Added Benefit of Onsite Group Support.

OBJECTIVE: The objective of this study is to determine the effectiveness of an 8-week web-based, mindfulness stress management program (WSM) in a corporate call center and added benefit of group support. METHODS: One hundred sixty-one participants were randomized to WSM, WSM with group support, WSM with group and expert clinical support, or wait-list control. Perceived stress, burnout, emotional and psychological well-being, mindfulness, and productivity were measured at baseline, weeks 8 and 16, and 1 year. RESULTS: Online usage was low with participants favoring CD use and group practice. All active groups demonstrated significant reductions in perceived stress and increases in emotional and psychological well-being compared with control. Group support improved participation, engagement, and outcomes. CONCLUSION: A self-directed mindfulness program with group practice and support can provide an affordable, effective, and scalable workplace stress management solution. Engagement may also benefit from combining web-based and traditional CD delivery.

Heart rate recovery is an important predictor of outcomes in patients with connective tissue disease-associated pulmonary hypertension.

Reduced heart rate recovery (HRR) after exercise is associated with increased mortality in cardiac and pulmonary diseases. We sought to evaluate the association between HRR after the 6-minute walk test (6MWT) and outcomes in patients with connective tissue disease-associated pulmonary hypertension (CTD-PH). Data were obtained by review of the medical records. HRR was defined as the difference in heart rate at the end of the 6MWT and after 1 minute (HRR1), 2 minutes (HRR2), and 3 minutes (HRR3) of rest. All patients with pulmonary hypertension and a diagnosis of systemic sclerosis, systemic lupus erythematosus, or mixed connective tissue disease who underwent the 6MWT between August 1, 2009, and October 30, 2011, were included (n = 66). By Kaplan-Meier analysis, HRR1, HRR2, and HRR3 at different cutoff points were all good predictors, with HRR1 of <16 being the best predictor of time to clinical worsening (log-rank P < 0.0001), hospitalization (log-rank P = 0.0001), and survival (log-rank P < 0.003). By proportional hazards regression, patients with HRR1 of <16 were at increased risk of clinical worsening (hazard ratio [HR]: 6.4 [95% confidence interval (CI): 2.6-19.2]; P < 0.0001], hospitalization (HR: 6.6 [95% CI: 2.4-23]; P < 0.0001), and death (HR: 4.5 [95% CI: 1.6-15.7]; P = 0.003). Patients in the highest tercile (HRR1 of ≥19) were unlikely to have a clinical worsening event (HR: 0.1 [95% CI: 0.04-0.5]; P = 0.001], to be hospitalized (HR: 0.1 [95% CI: 0.02-0.5]; P = 0.001), or to die (HR: 0.3 [95% CI: 0.07-0.9]; P = 0.04]. In conclusion, in patients with CTD-PH, abnormal HRR1 (defined as HRR1 of <16) after the 6MWT is a strong predictor of clinical worsening, time to clinical worsening, survival, and hospitalization.

Evaluation of osteoconductive scaffolds in the canine femoral multi-defect model.

Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development of new bone regeneration methodologies that combine scaffolds, sources of osteogenic cells, and bioactive scaffold modifications. Promising biomaterials and scaffold fabrication methods were identified in laboratories at Rutgers, MIT, Integra Life Sciences, and Mayo Clinic. Scaffolds were fabricated from various materials, including poly(L-lactide-co-glycolide) (PLGA), poly(L-lactide-co-ɛ-caprolactone) (PLCL), tyrosine-derived polycarbonate (TyrPC), and poly(propylene fumarate) (PPF). Highly porous three-dimensional (3D) scaffolds were fabricated by 3D printing, laser stereolithography, or solvent casting followed by porogen leaching. The canine femoral multi-defect model was used to systematically compare scaffold performance and enable selection of the most promising substrate(s) on which to add cell sourcing options and bioactive surface modifications. Mineralized cancellous allograft (MCA) was used to provide a comparative reference to the current clinical standard for osteoconductive scaffolds. Percent bone volume within the defect was assessed 4 weeks after implantation using both MicroCT and limited histomorphometry. Bone formed at the periphery of all scaffolds with varying levels of radial ingrowth. MCA produced a rapid and advanced stage of bone formation and remodeling throughout the defect in 4 weeks, greatly exceeding the performance of all polymer scaffolds. Two scaffold constructs, TyrPC(PL)/TCP and PPF4(SLA)/HA(PLGA) (Dip), proved to be significantly better than alternative PLGA and PLCL scaffolds, justifying further development. MCA remains the current standard for osteoconductive scaffolds.