Compliance and Variability of Hospital Price Transparency in Total Knee and Hip Arthroplasty in the United States.

INTRODUCTION: On January 1, 2019, in an effort to improve price transparency, the Centers for Medicare and Medicaid Services (CMS) mandated that hospitals display chargemasters and pricing for diagnosis-related groups (DRGs) online. We examined the compliance of the 50 top orthopaedic hospitals, ranked by US News, with CMS's mandate and compared pricing. METHODS: The chargemaster and pricing of DRG codes related to total knee arthroplasty (TKA) and total hip arthroplasty (THA) (469, 470, 461, 462, 466, 467, and 468) were evaluated in the top 50 orthopaedic hospitals in the United States. Spearman rank correlation coefficients (ρ) were used to evaluate the association between DRG 469, 470, and 467 prices with geographic practice cost index (GPCI) work and practice expense values. RESULTS: Thirty-six of the 50 hospitals reported DRG pricing for THA and TKA. Of these hospitals, 15 had prices for all seven DRGs of interest; only 467, 469, and 470 were reported across all the 36 hospitals. Of the 14 hospitals without DRG information, 12 had nothing and two had unsatisfactory reporting. Prices for DRGs 469, 470, and 467 were moderately or weakly correlated with both GPCI work and GPCI practice expense. All correlation analyses were statistically significant (P < 0.05). DISCUSSION: In summary, compliance with CMS's 2019 rule was poor overall. Fourteen of the 50 hospitals did not adequately report any DRG pricing, and only 15 of the hospitals were fully compliant with the mandate. In addition to poor compliance, the reported costs had variation not strongly accounted for by established geographic differences.

Assessing the Relationship Between Bone Density and Loss of Reduction in Nonsurgical Distal Radius Fracture Treatment.

PURPOSE: Whether low bone mineral density affects loss of reduction for distal radius fractures (DRFs) managed without surgery is unknown. Our purpose was to understand how bone mineral density, based on second metacarpal cortical percentage (2MCP) measurement, affects DRF healing after nonsurgical treatment. METHODS: We retrospectively reviewed 304 patients from 2 health systems with DRFs treated without surgery. The AO classification, 2MCP (<50% indicating osteoporosis), and fracture stability based on Lafontaine criteria were determined from prereduction radiographs. Radial inclination, radial height, volar tilt, ulnar variance, and intra-articular stepoff were measured on initial and 6-week final follow-up radiographs and compared. Bivariate analysis was used to evaluate the association between Lafontaine criteria or 2MCP and changes in radiographic parameters. Radiographic parameters with significant associations in bivariate analysis were evaluated in multivariable models adjusted for age, sex, initial radiographic parameters, reduction status, and AO fracture type. RESULTS: Across all patients, after 6 weeks of nonsurgical treatment, ulnar variance (shortening of the radius) increased by an average of 1.4 mm. Bivariate analysis showed that lower 2MCP and unstable fractures per Lafontaine criteria were each significantly associated with an increase in ulnar variance (P < .05). In adjusted multivariable models, having both 2MCP less than 50% and an unstable fracture together was associated with an additional 1.2-mm increase in ulnar variance (P < .05). CONCLUSIONS: A 2MCP in the osteoporosis range and unstable fractures by Lafontaine criteria were each associated with a significant increase in ulnar variance after nonsurgical treatment for DRFs. Patients with unstable fractures and 2MCP less than 50% are likely to have an additional increase of greater than 1 mm in ulnar variance at the end of nonsurgical fracture treatment than patients with similar injuries, but without these features. Using initial radiographs to identify patients with low bone mineral density that may be at risk for more substantial loss of reduction can assist with decision making for managing DRFs. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

The Assessment of Quality, Accuracy, and Readability of Online Educational Resources for Platelet-Rich Plasma.

PURPOSE: To critically evaluate the quality, accuracy, and readability of readily available Internet patient resources for platelet-rich plasma (PRP) as a treatment modality for musculoskeletal injuries. METHODS: Using the 3 most commonly used Internet search engines (Google, Bing, Yahoo), the search term "platelet rich plasma" was entered, and the first 50 websites from each search were reviewed. The website's affiliation was identified. Quality was evaluated using 25-point criteria based on guidelines published by the American Academy of Orthopaedic Surgeons, and accuracy was assessed with a previously described 12-point grading system by 3 reviewers independently. Readability was evaluated using the Flesch-Kincaid (FK) grade score. RESULTS: A total of 46 unique websites were identified and evaluated. The average quality and accuracy was 9.4 ± 3.4 (maximum 25) and 7.9 ± 2.3 (maximum 12), respectively. The average FK grade level was 12.6 ± 2.4, which is several grades higher than the recommended eighth-grade level for patient education material. Ninety-one percent (42/46) of websites were authored by physicians, and 9% (4/46) contained commercial bias. Mean quality was significantly greater in websites authored by health care providers (9.8 ± 3.1 vs 5.9 ± 4.7, P = .029) and in websites without commercial bias (9.9 ± 3.1 vs 4.5 ± 3.2, P = .002). Mean accuracy was significantly lower in websites authored by health care providers (7.6 ± 2.2 vs 11.0 ± 1.2, P = .004). Only 24% (11/46) reported that PRP remains an investigational treatment. CONCLUSIONS: The accuracy and quality of online patient resources for PRP are poor, and the information overestimates the reading ability of the general population. Websites authored by health care providers had higher quality but lower accuracy. Additionally, the majority of websites do not identify PRP as an experimental treatment, which may fail to provide appropriate patient understanding and expectations. CLINICAL RELEVANCE: Physicians should educate patients that many online patient resources have poor quality and accuracy and can be difficult to read.

Long-term outcomes of cement in cement technique for revision endoprosthesis surgery.

BACKGROUND AND OBJECTIVE: Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been a standard-of-care option for decades. With increased patient survival, the incidence of failed endoprostheses requiring revision surgery has increased. Revision of cemented endoprotheses by cementing into the existing cement mantle (CiC) is technically demanding. METHODS: This is a retrospective review of our endoprosthesis database of 512 consecutive cemented endoprosthetic reconstructions performed for oncologic diagnoses between 1980 and 2014. A total of 54 implants (mean patient age 32 years, range 13-81) were revised with a CiC technique. Outcomes evaluated were prosthesis survival, revision surgery categorized according to the Henderson Failure Mode Classification, complications, and functional scores. RESULTS: Fifteen-year Kaplan-Meier survival rate was 34% for initial revision and 39% for subsequent revision implants. Mean revised Musculoskeletal Tumor Society (MSTS) Score was 27 at latest follow-up. Infection rate was 2%, 9%, and 13% for primary endoprostheses, initial revisions, and subsequent revisions, respectively. Limb salvage rate was 87%. CONCLUSIONS: At long-term follow up, endoprostheses revised with the CiC technique showed consistent 15-year survival from initial (34%) to subsequent (39%) revision. Despite a relatively high failure rate, these results are encouraging and demonstrate that this is a conservative, repeatable technique.

Superior Labrum Anterior-Posterior Tears in the National Football League.

BACKGROUND: Shoulder disorders are common in football players, with up to 50% of National Football League (NFL) recruits reporting a history of shoulder injuries. Superior labrum anterior-posterior (SLAP) tears are an entity with well-described detrimental effects on return to play in overhead-throwing athletes but with minimal data in contact athletes. PURPOSE: To identify the incidence, predisposing factors, and effect of SLAP tears in NFL athletes and prospects as well as the treatment patterns of NFL team physicians. STUDY DESIGN: Descriptive epidemiology study. METHODS: This study was a comprehensive analysis of SLAP tears in elite football players using a dual approach: (1) SLAP injuries recorded in the NFL Injury Surveillance System from 2000 to 2014 were evaluated by player position, type of play, days/games lost, and surgical intervention; (2) NFL Scouting Combine athletes from 2003 to 2011 with prior SLAP repair were evaluated for draft success, and drafted athletes were compared with matched controls for career length and performance scores. RESULTS: SLAP tears represented a small portion (3.1%) of shoulder injuries in NFL athletes from 2000 to 2014, occurring most commonly in offensive linemen (28%). Surgically treated SLAP tears (42%) resulted in more days missed than did nonoperatively managed tears (140.2 vs 21.5 days; P < .001) and more games missed (8.4 vs 2.6 games; P = .003). SLAP repairs were also rare in NFL Combine athletes (n = 25 of 2965 athletes), with most having been performed in offensive linemen (32%). As compared with control NFL Combine athletes without SLAP tears, those drafted into the NFL with prior SLAP repair played significantly fewer games (33.7 vs 48.3; P = .049) and had fewer game starts (19.6 vs 35.4; P = .036). CONCLUSION: In this comprehensive analysis of SLAP tears in elite football players, it is clear that these injuries have the potential to cause significant detriment to an athlete's career.

Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model.

Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 µg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro-computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.

The effect of rhBMP-2 in a novel, non-instrumented extremity nonunion model.

BACKGROUND: Pre-clinical models of bony nonunion typically employ critical-length defects. However, these models may not accurately reflect clinical practice since many nonunions are diagnosed without bone loss. We developed a non-displaced rat ulna fracture model in order to examine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with an absorbable collagen sponge (ACS) for nonunion treatment. METHODS: Transverse diaphyseal ulna fractures were created in 24 Sprague-Dawley rats. Eight animals (Group 1: Nonunion) received no further intervention. The remaining 16 animals were treated with 5 µg rhBMP-2/ACS at 8 weeks after the original intervention (Group 2: Nonunion + BMP) or at the time of initial injury (Group 3: Fresh fracture + BMP). RESULTS: In Group 1, 7 of 8 fractures demonstrated gross motion and a persistent radiographic gap (12.5% healing rate). In Groups 2 and 3, fractures healed at a rate of 75% (6 of 8 in each group) as determined by manual and radiographic evaluation. Biomechanical testing for torque load-to-failure and torsional stiffness demonstrated no significant difference between healed specimens treated with rhBMP-2. CONCLUSIONS: To our knowledge, this is the first description of a physiologic, non-stabilized, non-defect fracture nonunion model in a rodent. Furthermore, unlike previous nonunion models, the healing rates after treatment with rhBMP-2 are comparable to that of clinical data, suggesting that this model may provide an environment more representative of nonunions in humans.

Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.

Factors influencing arthrodesis rates in a rabbit posterolateral spine model with iliac crest autograft.

PURPOSE: The rabbit posterolateral intertransverse spine arthrodesis model has been widely used to evaluate spinal biologics. However, to date, the validity and reproducibility of performance of iliac crest bone graft, the most common and critical control group, has not been firmly established. We evaluated original research publications that utilized this model, identified which experimental conditions affected fusion rates, and developed an algorithm to predict fusion rates for future study designs. METHODS: A MEDLINE search was performed for publications through December, 2011 that utilized this model to evaluate fusion rates elicited by iliac crest autograft. All study parameters were recorded, and logistic regression analyses were performed to determine the effects of these variables on fusion rates as determined by either manual palpation or radiographs. RESULTS: Seventy studies with 959 rabbits in 102 groups met the inclusion criteria. Excluding studies that measured fusion at 4 or fewer weeks or intentionally tried to decrease the fusion rate, the overall fusion rate for autograft was 58.3 ± 16.3 % (mean ± SD) as determined by manual palpation and 66.4 ± 17.8 % by plain radiographs. Regression analysis demonstrated a difference between these outcome measures with a trend towards significance (p = 0.09). Longer time points and larger volumes of autograft resulted in significantly greater reported fusion rates (p < 0.0001 and p < 0.05, respectively). Neither strain, age, weight, nor vertebral level significantly affected fusion rates. CONCLUSIONS: Although experimental conditions varied across studies, time point evaluation and autograft volume significantly affected fusion rates. Despite some variability demonstrated across certain studies, we demonstrated that when the time point and volume of autograft were controlled for, the iliac crest control group of the rabbit posterolateral spinal arthrodesis model is both reliable and predictably affected by different experimental conditions.

Acromioclavicular joint injuries in the National Football League: epidemiology and management.

BACKGROUND: Previous studies investigating acromioclavicular (AC) joint injuries in professional American football players have only been reported on quarterbacks during the 1980s and 1990s. These injuries have not been evaluated across all position players in the National Football League (NFL). PURPOSE: The purpose of this study was 4-fold: (1) to determine the incidence of AC joint injuries among all NFL position players; (2) to investigate whether player position, competition setting, type of play, and playing surface put an athlete at an increased risk for this type of injury; (3) to determine the incidence of operative and nonoperative management of these injuries; and (4) to compare the time missed for injuries treated nonoperatively to the time missed for injuries requiring surgical intervention. STUDY DESIGN: Descriptive epidemiological study. METHODS: All documented injuries of the AC joint were retrospectively analyzed using the NFL Injury Surveillance System (NFLISS) over a 12-season period from 2000 through 2011. The data were analyzed by the anatomic location, player position, field conditions, type of play, requirement of surgical management, days missed per injury, and injury incidence. RESULTS: Over 12 NFL seasons, there were a total of 2486 shoulder injuries, with 727 (29.2%) of these injuries involving the AC joint. The overall rate of AC joint injuries in these athletes was 26.1 injuries per 10,000 athlete exposures, with the majority of these injuries occurring during game activity on natural grass surfaces (incidence density ratio, 0.79) and most often during passing plays. These injuries occurred most frequently in defensive backs, wide receivers, and special teams players; however, the incidence of these injuries was greatest in quarterbacks (20.9 injuries per 100 players), followed by special teams players (20.7/100) and wide receivers (16.5/100). Overall, these athletes lost a mean of 9.8 days per injury, with quarterbacks losing the most time to injury (mean, 17.3 days). The majority of these injuries were low-grade AC joint sprains that were treated with nonoperative measures; only 13 (1.7%) required surgical management. Players who underwent surgical management lost a mean of 56.2 days. CONCLUSION: Shoulder injuries, particularly those of the AC joint, occur frequently in the NFL. These injuries can result in time lost but rarely require operative management. Quarterbacks had the highest incidence of injury; however, this incidence is lower than in previous investigations that evaluated these injuries during the 1980s and 1990s.

A comparative evaluation of factors influencing osteoinductivity among scaffolds designed for bone regeneration.

Due to differing compositions, synthetic scaffolds developed for bone regeneration vary widely in efficacy. To quantify the impact of such differences on osteoinductivity, numerous parameters were examined. Absorbable collagen sponge (ACS), three ceramic-based carriers (#1-3) of varying compositions, mineralized allograft chips, and an experimental phosphoserine-rich nanofiber scaffold [S(P) gel] were compared in their ability to promote cell adhesion, proliferation/survival, growth factor binding/release, and osteogenic gene expression. Human preosteoblasts were found to adhere most efficiently to the S(P) gel, and the growth/survival was greatest on the S(P) and ACS scaffolds, with minimal growth seen on the allograft and Ceramic #3. In bone morphogenetic protein-2 (BMP-2) binding/release assays, ACS demonstrated a burst release pattern, whereas the allograft and the ceramics inefficiently released BMP-2. The S(P) gel showed the most ideal rates of growth factor binding and release. QPCR analyses showed significant differences in the CXCL12, CXCR4, and RANKL transcripts among the cells grown on these various scaffolds. Although some scaffolds showed an advantage over others in individual parameters, the nanofiber gel appears to provide the optimal balance in the factors important to osteoinductivity evaluated here.

Characterizing the host response to rhBMP-2 in a rat spinal arthrodesis model.

STUDY DESIGN: Prospective, randomized, controlled preclinical trial. OBJECTIVE: This study seeks to characterize the localized and systemic host response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a well established rodent spine arthrodesis model utilizing cytokine analysis and magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: Although high fusion rates are achieved with rhBMP-2 in the spine, several complications have also been reported, including a localized response leading to radiculitis and seroma formation. The mechanism in which this occurs clinically is yet unknown. METHODS: One hundred female Fischer rats underwent a posterolateral intertransverse lumbar spinal fusion, with paraspinal muscle tissue resection, using iliac crest autograft, type I absorbable collagen sponge (ACS), 10- or 100-µg rhBMP-2/ACS. The animals underwent magnetic resonance imaging evaluation, serum cytokine analysis, manual palpation, and gross tissue inspection at 2, 4, 7, 10, and 21 days, postoperatively. RESULTS: Qualitative evaluation of MR images demonstrated a transient fluid collection at the surgery site in the rhBMP-2 animals as early as 4 and 7 days that was greater than the autograft or ACS groups. Quantitative analysis on T2-weighted axial images demonstrated greater signal intensity in the rhBMP-2 animals compared with the ACS and autograft groups in a time-dependent fashion. Higher concentrations of several cytokines were also detected at 2, 4, and 7 days, including interleukin 1ß, interleukin 18, tumor necrosis factor α, macrophage inflammatory protein 1α, and monocyte chemotactic protein 1 in animals treated with rhBMP-2/ACS relative to ACS alone. CONCLUSION: Our data suggest that the in vivo host response to rhBMP-2 in an animal model may be associated with circulating proinflammatory and osteoclastic cytokines.

Comparison of color fundus photographs and fundus autofluorescence images in measuring geographic atrophy area.

PURPOSE: To assess the agreement between color fundus photographs (CFP) and fundus autofluorescence (FAF) images when measuring geographic atrophy (GA) area and reproducibility of measurements between graders. Frequency and disagreement types were also determined. METHODS: Eyes with GA secondary to age-related macular degeneration had CFP and FAF imaging on the same day. Seventy-two eyes from 72 patients were included in the analysis. Three graders calculated GA area using digital imaging software. Main outcome measures included agreement between graders for GA area on both FAF and CFP and agreement between both imaging modalities. RESULTS: The intraclass correlation for the 3 graders for FAF images was 0.99 (95% confidence interval, 0.98-0.99). For CFP, it was 0.96 (95% confidence interval, 0.94-0.97). The intraclass correlation between imaging modalities for Graders 1, 2, and 3 were 0.93, 0.85, and 0.87, respectively. Sensitivities to detect involvement of fovea (CFP, 86-97%; FAF, 72-93%) and specificities to detect sparing of fovea (CFP, 74-76%; FAF, 59-88%) overlapped between imaging modalities. CONCLUSION: Both CFP and FAF imaging are reliable for measuring GA area. Interobserver agreement was slightly higher for FAF images. Although the high agreement between modalities suggests that either would be appropriate for measuring GA area, using both may be the best approach for following GA progression.

Visual preferences for sex and status in female rhesus macaques.

Most primates are both highly visual and highly social. These qualities predict that visual cues to social variables, such as identity, sex, social status, and reproductive quality, would be intrinsically valuable and systematically attract attention. Supporting this idea, thirsty male rhesus macaques (Macaca mulatta) will forego fluid reward to view images of the faces of high-ranking males and the sexual skin of females. Whether female rhesus macaques, who experience dramatically different social pressures and reproductive costs than male macaques, also systematically and spontaneously value visual cues to social information remains untested experimentally. We probed the preferences of female rhesus macaques, given the opportunity to display an image from a known class of social stimuli or touch a second target to display a blank screen. We found that females preferred faces of high-status males and also images of the perinea of both males and females, but were not motivated to display images of subordinate males or control stimuli. These findings endorse the view that both male and female rhesus macaques-and presumably other highly social primates-seek information about other individuals in a way that matches the adaptive value of that information for guiding social behavior.

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein-2 in a rodent arthrodesis model.

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP-2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

Use of fundus autofluorescence images to predict geographic atrophy progression.

PURPOSE: Fundus autofluorescence imaging has been shown to be helpful in predicting progression of geographic atrophy (GA) secondary to age-related macular degeneration. We assess the ability of fundus autofluorescence imaging to predict rate of GA progression using a simple categorical scheme. METHODS: Subjects with GA secondary to age-related macular degeneration with fundus autofluorescence imaging acquired at least 12 months apart were included. Rim area focal hyperautofluorescence was defined as percentage of the 500-µm-wide margin bordering the GA that contained increased autofluorescence. Rim area focal hyperautofluorescence on baseline fundus autofluorescence images was assessed and categorized depending on the extent of rim area focal hyperautofluorescence (Category 1: ≤33%; Category 2: between 33 and 67%; Category 3: ≥67%). Total GA areas at baseline and follow-up were measured to calculate change in GA progression. RESULTS: Forty-five eyes of 45 subjects were included; average duration of follow-up was 18.5 months. Median growth rates differed among categories of baseline rim area focal hyperautofluorescence (P = 0.01 among Categories 1, 2, and 3; P = 0.008 for Category 1 compared with Category 3, Jonckheere-Terpstra test). CONCLUSION: A simple categorical scheme that stratifies the amount of increased autofluorescence in the 500-µm margin bordering GA may be used to differentiate faster and slower progressors.

Serotonin transporter genotype modulates social reward and punishment in rhesus macaques.

BACKGROUND: Serotonin signaling influences social behavior in both human and nonhuman primates. In humans, variation upstream of the promoter region of the serotonin transporter gene (5-HTTLPR) has recently been shown to influence both behavioral measures of social anxiety and amygdala response to social threats. Here we show that length polymorphisms in 5-HTTLPR predict social reward and punishment in rhesus macaques, a species in which 5-HTTLPR variation is analogous to that of humans. METHODOLOGY/PRINCIPAL FINDINGS: In contrast to monkeys with two copies of the long allele (L/L), monkeys with one copy of the short allele of this gene (S/L) spent less time gazing at face than non-face images, less time looking in the eye region of faces, and had larger pupil diameters when gazing at photos of a high versus low status male macaques. Moreover, in a novel primed gambling task, presentation of photos of high status male macaques promoted risk-aversion in S/L monkeys but promoted risk-seeking in L/L monkeys. Finally, as measured by a "pay-per-view" task, S/L monkeys required juice payment to view photos of high status males, whereas L/L monkeys sacrificed fluid to see the same photos. CONCLUSIONS/SIGNIFICANCE: These data indicate that genetic variation in serotonin function contributes to social reward and punishment in rhesus macaques, and thus shapes social behavior in humans and rhesus macaques alike.