Diminished Immune Cell Adhesion in Hypoimmune ICAM-1 Knockout Pluripotent Stem Cells.

Hypoimmune gene edited human pluripotent stem cells (hPSCs) are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive (e.g., T cell) immune responses, but have largely not addressed the innate immune cells (e.g., monocytes, neutrophils) that mediate inflammation and rejection processes occurring early after graft transplantation. We identified the adhesion molecule ICAM-1 as a novel hypoimmune target that plays multiple critical roles in both adaptive and innate immune responses post-transplantation. In a series of studies, we found that ICAM-1 blocking or knock-out (KO) in hPSC-derived cardiovascular therapies imparted significantly diminished binding of multiple immune cell types. ICAM-1 KO resulted in diminished T cell proliferation responses in vitro and in longer in vivo retention/protection of KO grafts following immune cell encounter in NeoThy humanized mice. The ICAM-1 KO edit was also introduced into existing first-generation hypoimmune hPSCs and prevented immune cell binding, thereby enhancing the overall hypoimmune capacity of the cells. This novel hypoimmune editing strategy has the potential to improve the long-term efficacy and safety profiles of regenerative therapies for cardiovascular pathologies and a number of other diseases.

Use of ultrasound enhancing agents in transesophageal echocardiography to improve interpretive confidence of left atrial appendage thrombus.

BACKGROUND: The value of ultrasound enhancing agents (UEA) in patients undergoing transesophageal echocardiography (TEE) for the exclusion of left atrial appendage (LAA) thrombi prior to direct current cardioversion (DCCV) is evolving. METHODS: We retrospectively identified 88 consecutive TEEs, where a commercial UEA was used during LAA interrogation. De-identified non-enhanced (pre-UEA) and enhanced cine loop images (post-UEA) from the same subjects were randomly reviewed by four expert readers in a blinded fashion. RESULTS: In 33% of the cases, UEA use was associated with a statistically insignificant improvement in physician confidence (scale, 0-3) in determining the presence or absence of a LAA thrombus (P = 0.071). In instances where non-enhanced images yielded an uncertain interpretation or when the left atrium contained spontaneous echo contrast (SEC), UEA use was associated with an improvement in interpretive confidence in 49% (P < 0.001) and 41% of the cases (P = 0.001), respectively. Overall, the absolute rate of hypothetical decision to proceed with DCCV rose by 9% with the application of UEA (P = 0.004). In instances where non-enhanced images were interpreted with limited confidence or when SEC was present, there were absolute increases of 16% (P < 0.001) and 21% (P < 0.001) in hypothetical procession to DCCV, respectively. In cases of a combination of limited interpretive confidence and SEC, UEA use was associated with a 29% absolute increase in the rate of procession to DCCV (P < 0.001). CONCLUSIONS: In patients undergoing TEE interrogation of the LAA, the use of UEA is associated with an increase in the level of interpretive confidence and higher rates of theoretical procession to DCCV.

Editorial Commentary: Is the Cure Worse Than the Disease? Harvesting Autologous Osteochondral Transfer Plugs for Treatment of Lesions of the Elbow.

For autologous osteochondral transfer procedures for osteochondritis dessicans of the elbow, surgeons usually use the knee or ribs as donor sites. This procedure is not without donor site complications. Finding local donor sites is important to reducing the overall morbidity of this procedure.

Editorial Commentary: Don't Forgot the Hip in Swimmers and Multisport Athletes.

Swimming results in significant and repetitive stress on the hip as well as other joints, and hip pain in swimmers should not be ignored. Stretching and strengthening are the mainstays of injury prevention, and recent literature supports that when indicated, femoroacetabular impingement surgical treatment in swimmers results in excellent outcomes including return to sport and frequently at a level of performance superior to pre-injury status.

Related Research and Arthroscopy: Increasing the Breadth of Arthroscopy and Arthroscopy Techniques.

An editorial goal is to increase the breadth of Arthroscopy and Arthroscopy Techniques. Our readers are more than arthroscopic surgeons and scientists. Rather, the health care providers and scientists who read our journals are, first and foremost, physicians, allied health practitioners, and academic intellectuals whose interests include improving individual and public health and welfare across a wide spectrum of scholarly topics. By reaching a broader audience, we hope to expand our contribution to arthroscopic and related surgery and continue to develop the potential of our subspecialty.

Editorial Commentary: Is the Information Gathered From Patient-Reported Outcome Worth the Time and Effort? Electronic Patient-Reported Outcome Data Collection Systems Result in Poor Response Rate.

There is an increasing demand for quality metrics and patient-reported outcomes from government agencies and insurance carriers. However, electronic patient-reported outcomes fail to achieve a significant response rate because they are too long and complicated. It is suggested that outcome scores for quality metrics need to be simplified to increase the response rate.

Editorial Commentary: When a Tie Is Still a Win: Systematic Reviews Showing No Difference Between Treatments May Not Be Generalizable to Individual Patients.

When a systematic review finds no difference between treatment options for a particular disorder, this could mean more than you think. Individual patients requiring shoulder Bankart repair are unique with respect to their demands and expectations and pathology. Surgeons should combine published principles with understanding of their own skills and their specific patient to optimize a treatment outcome.

Occlusion dose monitoring in amblyopia therapy: status, insights, and future directions.

Occlusion therapy remains the mainstay treatment of amblyopia, but its outcome is not assured or universally excellent. Many factors are known to influence treatment outcome, among which compliance is foremost. The occlusion dose monitor (ODM) removes one variable from the treatment equation, because it records the occlusion actually received by-rather than prescribed for-the child. Improvement observed can thus be quantitatively related to the patching received. This review summarizes the insights the ODM has provided to date particularly in elucidating the dose-response relationship. We are entering the era of personalized ophthalmology in which treatments will be tailored to the needs of the individual child and facilitated by the use of wearable monitors.

Research Pearls: The Significance of Statistics and Perils of Pooling. Part 2: Predictive Modeling.

The focus of predictive modeling or predictive analytics is to use statistical techniques to predict outcomes and/or the results of an intervention or observation for patients that are conditional on a specific set of measurements taken on the patients prior to the outcomes occurring. Statistical methods to estimate these models include using such techniques as Bayesian methods; data mining methods, such as machine learning; and classical statistical models of regression such as logistic (for binary outcomes), linear (for continuous outcomes), and survival (Cox proportional hazards) for time-to-event outcomes. A Bayesian approach incorporates a prior estimate that the outcome of interest is true, which is made prior to data collection, and then this prior probability is updated to reflect the information provided by the data. In principle, data mining uses specific algorithms to identify patterns in data sets and allows a researcher to make predictions about outcomes. Regression models describe the relations between 2 or more variables where the primary difference among methods concerns the form of the outcome variable, whether it is measured as a binary variable (i.e., success/failure), continuous measure (i.e., pain score at 6 months postop), or time to event (i.e., time to surgical revision). The outcome variable is the variable of interest, and the predictor variable(s) are used to predict outcomes. The predictor variable is also referred to as the independent variable and is assumed to be something the researcher can modify in order to see its impact on the outcome (i.e., using one of several possible surgical approaches). Survival analysis investigates the time until an event occurs. This can be an event such as failure of a medical device or death. It allows the inclusion of censored data, meaning that not all patients need to have the event (i.e., die) prior to the study's completion.

Editorial Commentary: Belt and Suspenders-Linked Single-Row Rotator Cuff Repair.

Rotator cuff repairs fail at the suture-soft tissue interface. The linked single-row repair technique may provide increased soft tissue pullout strength, but further study is needed.

Editorial Commentary: No 2 Hips Are the Same-Femoroacetabular Impingement May Be More Proximal in Patients With Developmental Dysplasia.

Every hip is unique. The area of cam impingement is more proximal in patients with borderline developmental dysplasia of the hip. It is important to recognize this to ensure successful treatment.

Treatment of Amblyopia Using Personalized Dosing Strategies: Statistical Modelling and Clinical Implementation.

PURPOSE: To generate a statistical model for personalizing a patient's occlusion therapy regimen. METHODS: Statistical modelling was undertaken on a combined data set of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS) and the Randomized Occlusion Treatment of Amblyopia Study (ROTAS). This exercise permits the calculation of future patients' total effective dose (TED)-that predicted to achieve their best attainable visual acuity. Daily patching regimens (hours/day) can be calculated from the TED. RESULTS: Occlusion data for 149 study participants with amblyopia (anisometropic in 50, strabismic in 43, and mixed in 56) were analyzed. Median time to best observed visual acuity was 63 days (25% and 75% quartiles; 28 and 91 days). Median visual acuity in the amblyopic eye at start of occlusion was 0.40 logMAR (quartiles 0.22 and 0.68 logMAR) and at end of occlusion was 0.12 (quartiles 0.025 and 0.32 logMAR). Median lower and upper estimates of TED were 120 hours (quartiles 34 and 242 hours), and 176 hours (quartiles 84 and 316 hours). The data suggest a piecewise linear relationship (P = 0.008) between patching dose-rate (hours/day) and TED with a single breakpoint estimated at 2.16 (standard error 0.51) hours/day, suggesting doses below 2.16 hours/day are less effective. CONCLUSION: We introduce the concept of TED of occlusion. Predictors for TED are visual acuity deficit, amblyopia type, and age at start of occlusion therapy. Dose-rates prescribed within the model range from 2.5 to 12 hours/day and can be revised dynamically throughout treatment in response to recorded patient compliance: a personalized dosing strategy.

Editorial Commentary: Google It!-Reliability of Medical Information Found on the Internet.

Patients use Google or other search engines to obtain information on various medical problems. This information is not always reliable, and physicians should direct patients to Web sites that are validated and reliable.

Editorial Commentary: Pitching Should Come With a Warning Label.

Pitching is not without risk of overuse injuries. Pitch counts have been instituted to reduce the risk, but Riff et al.'s article clearly demonstrates that as pitchers get older they do not adhere to these counts, which increases the risk of injury.

Editorial Commentary: Many Ways to Skin a Cat.

There are many ways to treat lateral epicondylitis. The authors of this study present 2 different methods, but one method has less operative cost and takes less time. As medicine evolves, we should take this into account when choosing one procedure over another.

Editorial Commentary: Risks Versus Benefits.

As orthopaedic surgeons, we are constantly weighing the risks versus benefits of the procedures we may perform in our patients. The study by Werner et al. can be used to better inform our patients of the risk of undergoing arthroscopy of the elbow, allowing the orthopaedic surgeon to better weigh the risks versus benefits of the procedure.

Editorial Commentary: Think Twice, Cut Once.

How much of the anterior acetabulum rim needs to be resected to reduce the impingement of the pincer lesion? Hellman et al. present 3 measurements that can be performed on routine radiographs so that the surgeon can preoperatively, intraoperatively, and postoperatively measure the amount resected from the anterior acetabulum rim.

Editorial Commentary: Reinventing the Anterior Cruciate Ligament.

Our goal as orthopaedic surgeons is to repair, reconstruct, and/or restore function and anatomy to our patients. A new study in this issue, commented upon here, represents another step toward helping surgeons recreate the anatomy of the native anterior cruciate ligament.

Editorial Commentary: Doc, Can You Inject Stem Cells in My Knee?

Stem cell therapy is one of the most promising treatments to restore and repair damaged articulate cartilage. Koh et al. present in this issue their study on the treatment of articulate cartilage defects with adipose derived stem cell. We believe that it is a matter of time to when stem cells will become cost effective and commercially available for the treatment of articulate cartilage injuries.

A content analysis of oral health messages in Australian mass media.

BACKGROUND: Social analysis regarding oral health and oral health promotion are almost non-existent in the Australian context. The usefulness of such exploration lies in framing and informing research methodologies and health promotion initiatives, and can improve our understanding of oral health behaviours and their social contexts. METHODS: We conducted a systematic content analysis of a random sample of popular Australian magazines, newspapers and television shows from May to September 2012. Our sample included the top three best-selling magazines, six weekly newspapers, one from each available Australian state, and the four highest ranked Australian prime time television shows and their associated commercials. RESULTS: Data comprised 72 hours of prime time television and 14,628 pages of hardcopy media. Seventy-one oral health related media 'incidents' were counted during a five-month period. Only 1.5% of incidents referenced fluoride and only two made dietary references. Women were represented almost six times more than men and the majority of oral health related incidents conveyed no social context (63%). CONCLUSIONS: Oral health messages conveyed in Australian media fail to provide a social context for preventive or health-promoting behaviours. In light of increased levels of oral disease and retention of natural teeth, more community based oral health promotion and support for oral health literacy would be prudent in the Australian context.