Intraoperative modification of total elbow arthroplasty implants.

BACKGROUND: Modification of total elbow arthroplasty (TEA) implants may be necessary in selected patients with substantial anatomic bone deformity or those undergoing revision surgery. The purpose of this study was to investigate the prevalence and consequences of implant modifications during TEA at our institution. We hypothesized that TEA implant modification would be more common in revisions than in primary replacements, and that it would not be associated with worse clinical outcomes or increased rates of radiographic or surgical complications directly related to the implant modification. METHODS: Elbows that had undergone TEA by any of 3 surgeons at our institution with use of intraoperative implant modification between January 1992 and October 2019 were retrospectively reviewed for the type of modification and complications. Complications were classified as definitely related, probably related, possibly related, or nonrelated to the implant's modification according to the consensus review by the 3 senior surgeons. A survey was sent out to surgeons outside of our institution to investigate whether intraoperative modification to TEA implants is a common clinical practice. RESULTS: A total of 106 implant components were modified during 94 of 731 TEA procedures (13%) in 84 of 560 patients. Implant modifications were performed in 60 of 285 revision cases (21%) compared with 34 of 446 (8%) primary cases (P < .0001). These included shortening the stem in 40 (44%), bending the stem in 16 (15%), notching the stem in 16 (15%), tapering the stem in 9 (9%), and a combination of 2 or more of these modifications in 19 implants (17%). Among the 55 index surgeries available for complication analysis, 40 complications occurred in 28 index surgeries (11 primary and 17 revisions; 25 patients), making the overall complication rate 51%. Of these 40 complications, 23 were considered independent of any implant modification. Of the remaining 17 complications, 9 were considered nonrelated to the implant modification, 6 were possibly related, and 2 were probably related to the implant modification. Therefore, the complication rate possibly related or probably related to implant modification was 15% (8 of 55). No complication was classified as definitely related to the implant modification. No implant breakage or malfunction occurred after any modification. A total of 442 survey responses were received representing 29 countries, of which 144 surgeons (39%) performed modification to implants during TEA procedures. DISCUSSION: This study confirmed our hypothesis that modification of TEA implants is not uncommon at our institution, particularly in revision arthroplasty. Surgeons should keep in mind that complications possibly related or probably related to implant modification were at minimum 15% and could have been as high as 30% if the patients lost to follow-up had all had complications. Implant modification may be necessary in some cases but should be exercised with thoughtful consideration and caution.

Joint Track Machine Learning: An Autonomous Method of Measuring Total Knee Arthroplasty Kinematics From Single-Plane X-Ray Images.

BACKGROUND: Dynamic radiographic measurements of 3-dimensional (3-D) total knee arthroplasty (TKA) kinematics have provided important information for implant design and surgical technique for over 30 years. However, current methods of measuring TKA kinematics are too cumbersome, inaccurate, or time-consuming for practical clinical application. Even state-of-the-art techniques require human-supervision to obtain clinically reliable kinematics. Eliminating human supervision could potentially make this technology practical for clinical use. METHODS: We demonstrate a fully autonomous pipeline for quantifying 3D-TKA kinematics from single-plane radiographic imaging. First, a convolutional neural network (CNN) segmented the femoral and tibial implants from the image. Second, those segmented images were compared to precomputed shape libraries for initial pose estimates. Lastly, a numerical optimization routine aligned 3D implant contours and fluoroscopic images to obtain the final implant poses. RESULTS: The autonomous technique reliably produces kinematic measurements comparable to human-supervised measures, with root-mean-squared differences of less than 0.7 mm and 4° for our test data, and 0.8 mm and 1.7° for external validation studies. CONCLUSION: A fully autonomous method to measure 3D-TKA kinematics from single-plane radiographic images produces results equivalent to a human-supervised method, and may soon make it practical to perform these measurements in a clinical setting.

Don't Shoot Me: Potential Consequences of Force-on-Force Training Modulate the Human Stress Response.

ABSTRACT: Jensen, AE, Bernards, JR, Hamilton, JA, Markwald, RR, Kelly, KR, and Biggs, AT. Do not shoot me: potential consequences of force-on-force training modulate the human stress response. J Strength Cond Res 37(9): 1761-1769, 2023-Close-quarters combat (CQC) engagements trigger the "fight-or-flight" response, activating the sympathetic nervous system and hypothalamic-pituitary-adrenal axis in response to perceived threats. However, it has yet to be shown if a force-on-force (FoF) CQC training environment will lead to adaptations in the physiological stress response or performance. United States Marines and Army infantry personnel participated in a 15-day CQC training program. The CQC program focused heavily on FoF training with the use of nonlethal training ammunition (NLTA). Data collections occurred on training days 1 and 15, during a simulated FoF-hostage rescue (HR) scenario and photorealistic target drill. For the FoF-HR, subjects were instructed to clear the shoot house, rescue the hostage, and only shoot hostile threat(s) with NLTA. The photorealistic target drills were similar, but replaced the role players in the FoF-HR with paper targets. Salivary alpha-amylase (sAA) and salivary cortisol were obtained immediately before entering and exiting the shoot house. Time to completion significantly decreased, between days 1 and 15, for both the FoF-HR and the photorealistic drills by 67.7 and 54.4%, respectively ( p < 0.05). Analyses revealed that the change in sAA, nonsignificantly, doubled from day 1 to 15 during FoF-HR ( p > 0.05), whereas the change in sAA decreased during the photorealistic drills across days ( p < 0.05). Cortisol was significantly higher during the FoF-HR in comparison to the photorealistic drills ( p < 0.05). These data suggest that potential consequences of FoF training heighten the stress response in conjunction with enhanced performance.

Capillary morphogenesis gene 2 (CMG2) mediates growth factor-induced angiogenesis by regulating endothelial cell chemotaxis.

Anthrax protective antigen (PA) is a potent inhibitor of pathological angiogenesis with an unknown mechanism. In anthrax intoxication, PA interacts with capillary morphogenesis gene 2 (CMG2) and tumor endothelial marker 8 (TEM8). Here, we show that CMG2 mediates the antiangiogenic effects of PA and is required for growth-factor-induced chemotaxis. Using specific inhibitors of CMG2 and TEM8 interaction with natural ligand, as well as mice with the CMG2 or TEM8 transmembrane and intracellular domains disrupted, we demonstrate that inhibiting CMG2, but not TEM8 reduces growth-factor-induced angiogenesis in the cornea. Furthermore, the antiangiogenic effect of PA was abolished when the CMG2, but not the TEM8, gene was disrupted. Binding experiments demonstrated a broad ligand specificity for CMG2 among extracellular matrix (ECM) proteins. Ex vivo experiments demonstrated that CMG2 (but not TEM8) is required for PA activity in human dermal microvascular endothelial cell (HMVEC-d) network formation assays. Remarkably, blocking CMG2-ligand binding with PA or CRISPR knockout abolishes endothelial cell chemotaxis but not chemokinesis in microfluidic migration assays. These effects are phenocopied by Rho inhibition. Because CMG2 mediates the chemotactic response of endothelial cells to peptide growth factors in an ECM-dependent fashion, CMG2 is well-placed to integrate growth factor and ECM signals. Thus, CMG2 targeting is a novel way to inhibit angiogenesis.

Teaching Instrumental Analysis during the Pandemic: Application of Handheld CO2 Monitors to Explore COVID-19 Transmission Risks.

The COVID-19 pandemic has posed a challenge for maintaining an engaging learning environment while using remote laboratory formats. In this work, we describe a Student Choice Project (SCP) in an undergraduate instrumental analysis course that was adapted for remote learning without sacrificing research-based learning goals. We discuss the implementation and assessment of this SCP, selected student results, and student feedback. Students were provided handheld carbon dioxide monitors and charged with designing and implementing an investigation centered on COVID-19 airborne transmission. The real-time monitors provided experience with a new analytical tool that demanded considerations and analysis not common to other methods discussed in the course. Students were motivated by the ability to design their own projects and by the real-world implications of their findings. They performed well for all assessments, reported a positive experience, and recommended these monitors be added to the typical repertoire of instrumentation for the course.

Measurements of Volatile Organic Compounds During the COVID-19 Lockdown in Changzhou, China.

The COVID-19 outbreak in 2020 prompted strict lockdowns, reduced human activity, and reduced emissions of air pollutants. We measured volatile organic compounds (VOCs) using a proton-transfer-reaction mass spectrometry instrument in Changzhou, China from 8 January through 27 March, including periods of pre-lockdown, strict measures (level 1), and more relaxed measures (level 2). We analyze the data using positive matrix factorization and resolve four factors: textile industrial emissions (62 ± 10% average reduction during level 1 relative to pre-lockdown), pharmaceutical industrial emissions (40 ± 20%), traffic emissions (71 ± 10%), and secondary chemistry (20 ± 20%). The two industrial sources showed different responses to the lockdown, so emissions from the industrial sector should not be scaled uniformly. The quantified changes in VOCs due to the lockdowns constrain emission inventories and inform chemistry-transport models, particularly for sectors where activity data are sparse, as the effects of lockdowns on air quality are explored.

AAPM MEDICAL PHYSICS PRACTICE GUIDELINE 2.b.: Commissioning and quality assurance of X-ray-based image-guided radiotherapy systems.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized.

Anatomic total shoulder arthroplasty for primary glenohumeral osteoarthritis is associated with excellent outcomes and low revision rates in the elderly.

BACKGROUND: The relative indications of anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA) continue to evolve. Some surgeons favor RSA over TSA for elderly patients with primary glenohumeral osteoarthritis (GHOA) and an intact rotator cuff due to fear of a postoperative (secondary) rotator cuff tear in this age group. However, RSA is associated with unique complications and a worse functional arc of motion compared with TSA. Therefore, it is important to understand the clinical outcomes and rates of revision surgery and secondary rotator cuff tears in elderly patients undergoing TSA. METHODS: Between January 1, 2010, and December 31, 2017, 377 consecutive TSAs were performed for primary GHOA in 340 patients 70 years of age or older. The mean age at surgery was 76.2 years (standard deviation [SD], 4.9). Clinical evaluation included pain, motion, and American Shoulder and Elbow Surgeons score. Radiographs were reviewed for preoperative morphology and postoperative complications. All complications and reoperations were recorded. The average clinical follow-up time was 3.3 years (SD, 2.0). Statistical analyses were performed, and Kaplan-Meier implant survival estimates were calculated. For all analyses, a P value <.05 was considered statistically significant. RESULTS: The mean pain visual analog scale and American Shoulder and Elbow Surgeons score at the final follow-up were 1.6 (SD, 2.2) and 78.0 (SD, 17.8), respectively. Forward elevation and external rotation increased from 96° (SD, 30°) and 26° (SD, 20°) preoperatively to 160° (SD, 32°) and 64° (SD, 26°) postoperatively (P < .001 for each). The percentage of patients who had internal rotation to L5 or greater increased from 24.8% preoperatively to 71.8% postoperatively (P < .001). Revision surgery was performed in 3 shoulders (0.8%), and the 5-year implant survival estimate was 98.9% (95% confidence interval: 97.3%-100%). There were 3 medical (0.8%), 10 minor surgical (2.7%), and 5 major surgical (1.3%) complications. No shoulder had radiographic evidence of humeral component loosening, whereas 7 (2%) had evidence of some degree of glenoid component loosening. In total, there were 5 secondary rotator cuff tears (1.3%), of which 2 (0.5%) required revision surgery. CONCLUSION: Elderly patients with primary GHOA and an intact rotator cuff have excellent clinical and radiographic outcomes after anatomic TSA, with high implant survival rates and a low incidence of secondary rotator cuff tears in the first 5 postoperative years. Age greater than 70 by itself should not be considered an indication for RSA over TSA.

Players' perspectives on successfully returning to professional baseball after medial ulnar collateral ligament reconstruction.

BACKGROUND: As the incidence of ulnar collateral ligament reconstruction (UCLR) surgery continues to rise, an improved understanding of baseball pitchers' perspectives on the postoperative recovery process and return to pitching is needed. The purpose of this study was to analyze pitchers' perspectives on recovery after UCLR. METHODS: dDuring the 2018 baseball season, an online questionnaire was distributed to the certified athletic trainers of all 30 Major League Baseball (MLB) organizations. These athletic trainers then administered the survey to all players within their organization including MLB and 6 levels of Minor League Baseball. MLB or Minor League Baseball pitchers who had previously undergone UCLR and participated in a rehabilitation program (or were currently participating in one at time of the survey) were included in the study. RESULTS: There were 530 professional pitchers who met inclusion criteria. The majority (81%) of pitchers began rehabilitation within 2 weeks of surgery, with 51% beginning within 1 week. The majority of pitchers began a long-toss throwing program at 5 and 6 months after surgery (27% and 21%), with 52% making their first throw off a mound between 7 and 9 months. The number of pitchers who participated in a weighted ball throwing program decreased significantly after surgery (20%-11%, P < .001). After UCLR, 56% of pitchers reported no changes regarding pitching mechanics or types of pitches thrown, 42% reported changed mechanics, and only 3% either decreased or stopped throwing a certain pitch type. Overall, 54% believed that their current throwing velocity was faster than their velocity before ulnar collateral ligament injury. Twenty percent of pitchers reported experiencing a setback that resulted in temporary stoppage of their rehabilitation program, the most common reason being flexor tightness or tendonitis (53%). Seventy-six percent reported that they were not concerned about sustaining another elbow injury; however, significantly less (61%; P < .001) stated that they would have UCLR again if necessary. CONCLUSIONS: Although UCLR is generally reported to have excellent clinical outcomes, 20% of pitchers experienced a significant setback during their rehabilitation and only 61% of pitchers, having gone through UCLR and the subsequent recovery, would be willing to undergo revision surgery and repeat the rehabilitation process if it were to become necessary. In addition, 42% of pitchers felt that they had to alter their throwing mechanics to return to pitching. Surgeons and athletic trainers should aim to understand the UCLR recovery process from the pitchers' perspective to better counsel future patients recovering from UCLR.

Landscape structure and climate drive population dynamics of an insect vector within intensely managed agroecosystems.

Characterizing factors affecting insect pest populations across variable landscapes is a major challenge for agriculture. In natural ecosystems, insect populations are strongly mediated by landscape and climatic factors. However, it has proven difficult to evaluate if similar factors predict pest dynamics in agroecosystems because control tactics exert strong confounding effects. We addressed this by assessing whether species distribution models could effectively characterize dynamics of an insect pest in intensely managed agroecosystems. Our study used a regional multi-year data set to assess landscape and climatic drivers of potato psyllid (Bactericera cockerelli) populations, which are often subjected to calendar-based insecticide treatments because they transmit pathogens to crops. Despite this, we show that psyllid populations were strongly affected by landscape and climatic factors. Psyllids were more abundant in landscapes with high connectivity, low crop diversity, and large natural areas. Psyllid population dynamics were also mediated by climatic factors, particularly precipitation and humidity. Our results show that many of the same factors that drive insect population dynamics in natural ecosystems can have similar effects in an intensive agroecosystem. More broadly, our study shows that models incorporating landscape and climatic factors can describe pest populations in agroecosystems and may thus promote more sustainable pest management.

Regulation of metabolism during hibernation in brown bears (Ursus arctos): Involvement of cortisol, PGC-1α and AMPK in adipose tissue and skeletal muscle.

The purpose of this study was to investigate changes in expression of known cellular regulators of metabolism during hyperphagia (Sept) and hibernation (Jan) in skeletal muscle and adipose tissue of brown bears and determine whether signaling molecules and transcription factors known to respond to changes in cellular energy state are involved in the regulation of these metabolic adaptations. During hibernation, serum levels of cortisol, glycerol, and triglycerides were elevated, and protein expression and activation of AMPK in skeletal muscle and adipose tissue were reduced. mRNA expression of the co-activator PGC-1α was reduced in all tissues in hibernation whereas mRNA expression of the transcription factor PPAR-α was reduced in the vastus lateralis muscle and adipose tissue only. During hibernation, gene expression of ATGL and CD36 was not altered; however, HSL gene expression was reduced in adipose tissue. During hibernation gene expression of the lipogenic enzyme DGAT in all tissues and the expression of the FA oxidative enzyme LCAD in the vastus lateralis muscle were reduced. Gene and protein expression of the glucose transporter GLUT4 was decreased in adipose tissue in hibernation. Our data suggest that high cortisol levels are a key adaptation during hibernation and link cortisol to a reduced activation of the AMPK/PGC-1α/PPAR-α axis in the regulation of metabolism in skeletal muscle and adipose tissue. Moreover, our results indicate that during this phase of hibernation at a time when metabolic rate is significantly reduced metabolic adaptations in peripheral tissues seek to limit the detrimental effects of unduly large energy dissipation.

Establishing the learning curve for elbow arthroscopy: surgeon and trainee perspectives on number of cases needed and optimal methods for acquiring skill.

BACKGROUND: Elbow arthroscopy has increased in frequency as its indications have widened. Despite this growth, a learning curve has not yet been defined. HYPOTHESIS: We hypothesized that there would be significant differences in perspective between trainees and established surgeons for the number of cases needed to reach each skill level and what they felt are the most valuable training tools. METHODS: Orthopedic attending physicians and trainees were asked to complete a questionnaire assessing participant demographics, case volumes required to reach defined skill levels (novice, safe, competent, proficient, and expert), and the efficacy of various learning methodologies for elbow arthroscopy. The value of educational methods was assessed using a 5-point Likert scale (1 = not at all valuable; 5 = extremely valuable). RESULTS: The study population consisted of 323 total participants, of whom 224 (69.3%) were attending surgeons and 99 (30.7%) were trainees (resident or fellow physicians). According to the attending physicians, the mean numbers of cases needed to reach each skill level were 19 to be safe, 42 to be competent, 93 to be proficient, and 230 to be expert. These case numbers were not significantly different from the perspectives of trainees. Across the respondents, there were no significant differences in the number of cases needed to reach each level of skill based on the respondents' level of training, years of experience, type of fellowship, or self-reported skill level.Although both groups highly valued live surgery (4.7 of 5) and cadaveric practice (4.6 of 5) for acquiring skill, attendings placed higher value on reading (4.0 vs. 3.3, P < .001), videos/live demos (4.2 vs. 3.6, P < .001), and formal courses (4.5 vs. 4.1, P < .001) than trainees. Both groups place relatively low value on surgical simulators (2.8-3.6). CONCLUSIONS: There was considerable agreement among attending surgeons and trainees in terms of the number of cases needed to attain various skill levels of elbow arthroscopy, which was consistent regardless of fellowship background, self-reported skill level, career length, and elbow arthroscopy case volume. However, there was some disagreement between attending surgeons and trainees over the most valuable methods for acquiring surgical skill with trainees placing less value on textbooks, surgical videos, and formal courses compared with attending surgeons. An understanding of the elbow arthroscopy learning curve will help trainees and their training programs establish case volume targets before safe, independent practice. Future studies should aim to clinically validate this learning curve.

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.

BACKGROUND: Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use. QUESTIONS/PURPOSES: The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection. METHODS: Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining. RESULTS: Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005). CONCLUSIONS: Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing. CLINICAL RELEVANCE: This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.

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.

Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor ß-positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff.

BACKGROUND AND HYPOTHESIS: After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor ß (PDGFRß) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRß+ progenitor cells that contribute to fibroadipogenesis of the rotator cuff. METHODS: We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRß+ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP+ PDGFRß+ PDGFRα+ cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. RESULTS: GFP+ PDGFRß+ PDGFRα+ cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRß+ PDGFRα+ cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRß+ PDGFRα+ cells were highly adipogenic and significantly more fibrogenic than PDGFRß+ PDGFRα- cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRß+ PDGFRα+ cells. CONCLUSION: PDGFRß+ PDGFRα+ cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRß+ PDGFRα+ cells in vitro. Clinically, perioperative PDGFRß+ PDGFRα+ cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears.

The effect of training on lumbar spine posture and intervertebral disc degeneration in active-duty Marines.

Military training aims to improve load carriage performance and reduce risk of injuries. Data describing the lumbar spine (LS) postural response to load carriage throughout training are limited. We hypothesised that training would reduce the LS postural response to load. The LS posture of 27 Marines was measured from upright MR images: with and without load (22.6 kg) at the beginning, middle, and end of School of Infantry (SOI) training. Disc degeneration was graded at L5-S1. No changes in posture and disc degeneration were found throughout training. During load carriage the LS became less lordotic and the sacrum more horizontal. Marines with disc degeneration had larger sacral postural perturbations in response to load. Our findings suggest that the postural response to load is defined more by the task needs than by the physical condition of the Marine. Practitioner Summary: The effect of military training on lumbar spine posture is unknown. The lumbar posture of 27 Marines was measured from upright MR images, with and without load throughout infantry training. No changes in posture or IVD degeneration were found across training. Marines with degeneration at the L5-S1 level had larger sacral postural perturbations in response to load.

Influence of patient's physiologic factors and immobilization choice with stereotactic body radiotherapy for upper lung tumors.

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full-length BodyFIX and thermoplastic S-frame. At simulation, free-breathing, four-dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in-room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone-beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT-based shifts for treatment was 2, 2, and 4 mm in left-right, anterior-posterior, and cranial-caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three-dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S-frame to 17 tumors. Of these tumors, 41 were non-small cell lung cancer and 15 were metastatic from other sites. Lesions measured < 1 (15%), 1.1 to 2 (50%), 2.1 to 3 (25%), and > 3 (11%) cm. Errors from first shifts of first fractions were significantly less with S-frame than BodyFIX (p < 0.001). No difference in local control (LC) was found between S-frame and BodyFIX (p = 0.35); two-year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S-frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.