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Background: Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men. Purpose: To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL. Study Design: Systematic review; Level of evidence, 4. Methods: Searches were conducted using MEDLINE (1946–August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included athletic injuries, knee injuries, ligaments, joint instability, menstrual cycle, ovulation, hormones, and contraceptives. Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Results: Twenty-one studies totaling 68,758 participants were included: 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase. Conclusion: The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.

Background Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized. Methods In this study, cell lysates and exosomes from two derivatives (HMPOS-2.5R and HMPOS-10R) of the HMPOS osteosarcoma cell line generated by repeated carboplatin treatment and recovery, were characterized proteomically by mass spectrometry. Protein cargos of circulating serum exosomes from dogs with naturally occurring osteosarcoma, were also assessed by mass spectrometry, to identify biomarkers that discriminate between good and poor responders to carboplatin therapy. Results Both cell lysates and exosomes exhibited distinct protein signatures related to drug resistance. Furthermore, exosomes from the resistant HMPOS-2.5R cell line were found to transfer drug resistance to drug-sensitive HMPOS cells. The comparison of serum exosomes from dogs with a favorable disease-free interval [DFI] of > 300 days, and dogs with < 100 days DFI revealed a proteomic signature that could discriminate between the two cohorts with high accuracy. Furthermore, when the patient’s exosomes were compared to exosomes isolated from carboplatin resistant cell lines, several putative biomarkers were found to be shared. Conclusions The findings of this study highlight the significance of exosomes in the potential transfer of drug resistance, and the discovery of novel biomarkers for the development of liquid biopsies to better guide personalized chemotherapy treatment.

Yousafzai's galvanizing story of being shot by the Taliban for encouraging girls to attend school was being read by third graders; posters depicting Gonzalez along with the slogan We Call BS decorated not only the offices of progressive professors but also corporate storefronts; and an international surge in youth activism on social media was being attributed to Thunberg and widely recognized as \"the Greta Effect.\" [...]our hopes were set on what looked like an increase-could it be a movement wave?- in organized student resistance on university and college campuses across the US. [...]they are much harder to capture in the mainstream media than the charismatic, and usually telegenic, individuals who might come to represent resistance. [...]worthwhile teaching must be political. [...]to make any meaningful change inside the educational institutions where we work, we have to join movements and work for radical change outside of them.

The differentiation of the bacterium Bacillus subtilis into a dormant spore is among the most well-characterized developmental pathways in biology. Classical genetic screens performed over the past half century identified scores of factors involved in every step of this morphological process. More recently, transcriptional profiling uncovered additional sporulation-induced genes required for successful spore development. Here, we used transposon-sequencing (Tn-seq) to assess whether there were any sporulation genes left to be discovered. Our screen identified 133 out of the 148 genes with known sporulation defects. Surprisingly, we discovered 24 additional genes that had not been previously implicated in spore formation. To investigate their functions, we used fluorescence microscopy to survey early, middle, and late stages of differentiation of null mutants from the B. subtilis ordered knockout collection. This analysis identified mutants that are delayed in the initiation of sporulation, defective in membrane remodeling, and impaired in spore maturation. Several mutants had novel sporulation phenotypes. We performed in-depth characterization of two new factors that participate in cell-cell signaling pathways during sporulation. One (SpoIIT) functions in the activation of σE in the mother cell; the other (SpoIIIL) is required for σG activity in the forespore. Our analysis also revealed that as many as 36 sporulation-induced genes with no previously reported mutant phenotypes are required for timely spore maturation. Finally, we discovered a large set of transposon insertions that trigger premature initiation of sporulation. Our results highlight the power of Tn-seq for the discovery of new genes and novel pathways in sporulation and, combined with the recently completed null mutant collection, open the door for similar screens in other, less well-characterized processes.

Objectives: As the number of females entering the field of orthopaedic surgery increases, more attention will be paid to the safety aspects of radiation, including those surrounding pregnancy and female-specific cancers. The purpose of this study was to survey a diverse cross-section of U.S. female orthopedic surgeons evaluating their education and attitudes on radiation safety as well as adherence to safety recommendations. Methods: An online survey was distributed via the Ruth Jackson Orthopaedic Society (RJOS), The Women in Orthopaedics Facebook group, and the Forum. The first component of the survey included demographic information. The second component assessed radiation safety knowledge. The third component was designed to capture personal experiences among respondents. Respondents indicated how frequently they were exposed to radiation, their satisfaction with radiation safety training, their radiation safety practices, and their level of concern regarding exposure risk. Data were collected using REDCap. Results: Sixty-six female orthopaedic surgeons from 21 states completed the survey. Most respondents were between 30-49 years old (77.3%), and most (62.1%) had been practicing for 0-9 years. Regular dosimeter usage was reported by 24.2% of respondents, and 36.4% of respondents reported always having radiation protective equipment provided that correctly fit them. Less than half (48.5%) of respondents had lectures in their training devoted to radiation safety, and 48.5% felt they had adequate knowledge of radiation safety. Regarding their radiation safety training, 60.6% of respondents rated their training as unsatisfactory or extremely unsatisfactory, and 90.9% of respondents stated that they think training efforts for radiation safety can improve. Conclusions: Advancements are needed in radiation safety training, particularly regarding practices related to health and pregnancy risk. Assessment of radiation safety knowledge and personal adherence to guidelines can promote improvements in safety measures and increase confidence of female orthopaedic surgeons in their safety and knowledge of radiation exposure.

Objectives: Patellofemoral instability (PFI) is a challenging disorder that disrupts the function and quality-of-life of affected patients. Although advances have been made in interventions that restore stability and protect the patellofemoral joint from early deterioration, it is not clear whether the diagnosis and treatment of PFI has been equitable between racial and socioeconomic groups. This study’s purpose was to determine the effects of race and socioeconomic disadvantage on the severity of patellar instability at initial presentation. Methods: A prospectively enrolled, multicenter cohort study (JUPITER: Justifying Patellar Instability Treatment by Results) database, with this question determined a priori, was queried for patients enrolled between December 2016 and September 2022 who had 5-digit zip code data available. Patients were excluded if zip code, race, history, treatment, or baseline patient-reported outcome (PROM) data was unavailable. Patients enrolled bilaterally were reduced to their first enrolled knee, and their contralateral knee excluded, to avoid duplicate counting of race or socioeconomic data. National percentile area deprivation index (ADI) rankings were calculated for each 5-digit zip code and stratified by ADI (low (Q1), medium (Q2-Q3), high (Q4)), where higher ADI indicates greater socioeconomic disadvantage. To improve power of analysis, race was categorized into White, Black, or Other race, which included subjects who were Asian, Hispanic, Native American, Native Hawaiian, Indian, Cape Verdean, and multiracial, as well as patients who selected “Other race” but did not specify (Table 1). ANOVA analysis was performed to analyze differences in means between the three ADI groups. Analysis was conducted using generalized linear mixed models incorporating age, gender, BMI, race/ethnicity, and ADI category as fixed effects. A random residual effect for organization was included to adjust for clustering by hospital. Interaction terms were considered between race/ethnicity and ADI in each model and included where significant. Outcomes analyzed in this model included first-time vs. recurrent dislocator status at time of intervention, number of dislocations at time of treatment, type of treatment (isolated medial patellofemoral ligament reconstruction (MPFL-R) vs. MPFL-R + Tibial Tubercle Osteotomy (TTO), patellofemoral chondroplasty, osteochondral fracture treatment), presence and location of Outerbridge Grade III/IV chondral lesions, and baseline patient-reported outcome measures (KOOS Pain, KOOS QOL, Banff Patellar Instability Index 2.0, IKDC). Results: 1215 unique patients (16.6 ± 4.12 years old, 61.7% female) had available zip code, race, ADI, history, treatment, and baseline PROM data. Mean national ADI percentile rank was 38.1 ± 7.6 (Q2-Q3). Patients in the high ADI group were more frequently Black (13% vs. 3.2% in the Low ADI group, p < 0.0001), and patients in the high ADI group had a significantly higher mean BMI than the Low ADI group (24.95 ± 8.5 vs. 23.04 ± 6.34, p = 0.0001). High ADI patients were less likely to undergo chondroplasty (33.8% vs. 45.1%, p = 0.0041) and less likely to undergo osteochondral fracture treatment (9.8% vs. 17.3%, p = 0.0099) than their low ADI counterparts (Table 2). High ADI patients also had a lower baseline KOOS Pain score than Low ADI patients (66.8 ± 22.4 vs. 71.1 ± 22.5, p = 0.0483) (p=0.0167). There were no significant differences in baseline KOOS QOL, IKDC, or BPII 2.0 based on ADI (p > 0.05) (Table 3). For the generalized linear mixed models (Table 4), Other race patients were more likely to be First-Time Dislocators, whereas Female patients and patients with a higher BMI where more likely to be a recurrent dislocator. Black race, high ADI, and being both of Black race and High ADI were predictive of an increased number of dislocations at the time of presentation. Being female and older age were each associated with a decreased KOOS Pain score at presentation. Race and ADI did not have a statistically significant association with any of the four baseline PROM scores. Conclusions: Patellar instability patients with greater socioeconomic disadvantage (higher ADI) were more often Black and had a higher mean BMI than those of lower ADI. Higher ADI was associated with worse pain scores at baseline and a lower likelihood of undergoing chondroplasty and osteochondral fracture treatment. Higher ADI was also associated with more dislocations before presentation. Understanding the role of race and socioeconomic status in the treatment of patients with patellar instability will be helpful to optimize the workup and treatment of this disorder among disadvantaged groups. Future studies are warranted to examine the short- and long-term outcomes of patients treated for patellar instability based on race and socioeconomic status.

Objectives: Current standard of care after a First-Time patellar instability event is non-operative management, with exceptions for patients with osteochondral fracture or loose body requiring immediate surgical intervention, patients with significant pathoanatomy, or contralateral patellar instability. For recurrent patellar instability, there is controversy as to when isolated medial patellofemoral ligament reconstruction (MPFL-R) is enough. The purpose of this study is to determine (1) the comparative outcomes of isolated MPFL-R after first-time patellar instability (FTPI) and recurrent patellar instability (RPI) and (2) the impact of osteochondral injury on outcomes after surgical treatment of FTPI. Methods: A prospective, multicenter cohort study (JUPITER: Justifying Patellar Instability Treatment by Results) database was queried for patients who underwent patellar stabilization surgery (PSS) between December 2016 and September 2022. Patients were included if they underwent a medial patellofemoral ligament reconstruction (MPFL-R) for FTPI or RPI. Those with less than 2 years of clinical follow-up, revision PSS, or concomitant bony procedures at the time of MPFL-R were excluded. Independent t-tests were performed to compare means for continuous variables, and chi-squared tests were performed to compare frequency for categorical variables, between groups. Results: A total of 739 patients met inclusion criteria with a mean age of 15.6 ± 3.3 years, and 59.9% female sex. FTPI occurred in 216 (27.2%) patients, and of these 104 (48.1%) sustained an operative chondral or osteochondral lesion. Those with FTPI had a significantly greater trochlear depth (2.9 mm vs. 2.6 mm; P = .048), but a significantly lower rate of pathological trochlear bump > 5 mm (52.3% vs. 67.8%; P = .008) than those with RPI (Table 1). Among the FTPI cohort, those with treatment of a chondral lesion were less likely to have patella alta (Caton-Deschamps Index > 1.3) (14.9% vs. 41.3%, P = .006), and less frequently had a mild or severe J-sign (25.0% vs. 42.7%, p = .016) than those without a chondral intervention (Table 2). Postoperatively, there were no differences with rates of recurrent instability (8.3% vs. 12.3%; P = .130) or return to sport (90.4% vs. 94.5%; P = .182) between FTPI and RPI, respectively (Table 3). There were no differences with rates of recurrent instability (7.6% vs. 9.1%; P = .807) or return to sport (89.1% vs. 91.7%; P = .755) between those with or without a chondral intervention, respectively (Table 4). Conclusions: This study demonstrates no difference in rates of recurrent post-operative instability between FTPI and RPI with rates consistent with the current literature. MPFL reconstruction remains as a durable surgical treatment option for patients presenting with either FTPI or RPI with relatively low rates of recurrent instability. In this patient population, patella alta was found to be protective of osteochondral injury which is also consistent with existing literature. Continued, long-term investigation is needed to understand outcomes for First-Time patellar instability and to better define the indications for surgical interventions in this population.

Objectives: To compare the cost-effectiveness of nonoperative treatment, immediate operative treatment, and delayed operative treatment for first-time and recurrent episodes of patellar instability. Further, this study investigates the cost-effectiveness of medial patellofemoral ligament reconstruction (MPFL-R) versus medial patellofemoral ligament reconstruction with tibial tubercle osteotomy (MPFL-R with TTO). Methods: Using the Justifying Patellar Instability Treatment by Results (JUPITER) cohort, patients were prospectively enrolled between 2017-2022 if they were ages 10-35, had 1-year follow-up or more for treatment of patellar instability, did not have need for multi-ligamentous reconstruction, and completed all required follow-up assessments. Those who underwent previous ipsilateral knee surgery were excluded. Patients were categorized into first-time patellar or recurrent patellar dislocation, then subsequently categorized based on their treatment plan: nonoperative, initial operative, or delayed operative. Each group was further divided into three lifestyle alteration states: 1) severe/total alteration or lifestyle, 2) mild/moderate alteration of lifestyle, and 3) no alteration of lifestyle. The responses from the Knee Injury and Osteoarthritis Outcome Score (KOOS) Q2 question (“Have you modified your lifestyle to avoid potentially damaging activities to your knee?”) were used categorize patients in these states. Each lifestyle state was assigned a Quality Adjusted Life Year (QALY) score from 0-1, with 1 representing perfect health. This QALY score was an average of the patients’ Banff Patellofemoral Instability Instrument (BPII) (score for the annual assessment of patellofemoral treatment effectiveness) in each lifestyle state. A Markov state transition model was constructed to assess the cost-effectiveness of each treatment modality for first time and recurrent patellar instability. The Markov model ran for 10 cycles, representing cost-effectiveness outcomes 10 years following initiation of treatment. Transition state probabilities between lifestyle states from initiation of treatment to 2 years were modeled using JUPITER derived probabilities. Transition state probabilities from years 2-10 were derived from existing literature. Cost of surgery, physical therapy, parental leave, and bracing were also derived from current literature and adjusted to inflation. A final ratio was used to compare cost-effectiveness between treatment modalities.   Results: There were 307 First Time Dislocators and 380 Recurrent Dislocators that met inclusion criteria. A total of 257 patients underwent MPFL-R and 73 patients MPFLR with TTO. For first-time dislocators, a QALY score of .35 was associated with severe/total lifestyle alterations, .65 was associated with mild/moderate lifestyle alterations, and a score of .85 was associated with no. Comparative QALY scores for the recurrent dislocators group were 0.35, 0.64, and 0.87. QALY scores for the MPFLR surgical treatment group were greater compared to the MPFL-R with TTO group. Over a 2-year time-period, operative treatment had the highest QALY accruals out of all treatment modalities for both first time and recurrent dislocators, whereas delayed operative treatment had the lowest. Further analysis showed MPFLR without any concurrent bony procedures having a higher QALY accrual compared to MPFLR with TTO. Conclusions: Over a two-year period, operative treatment provided the highest utility amongst patients with first-time and recurrent patellar dislocations. Delayed operative treatment led to the lowest utility scores, emphasizing the importance of choosing the correct treatment modality from patients’ initial presentation and avoiding delay of definitive treatment. Lastly, isolated MPFL-R led to higher utility scores than MPFL-R with TTO, proving to be a more cost-effective form of operative treatment, giving providers another metric when ultimately deciding which operative measure to perform. Given that MPFL-R treatment provides the highest utility of all, there is further support for its utilization among both first-time and recurrent patellar dislocations as the standard treatment for patellar instability.

Objectives: The utility of Examination under anesthesia (EUA) for patellar instability is such that a negative EUA or inability to dislocate patella under anesthesia cannot rule out patellar instability but a positive EUA or ability to dislocate the patella under anesthesia can confirm the diagnosis of patellar instability. Examination under anesthesia (EUA) has been helpful for evaluation of stability of various joints, including elbow, hip, knee and shoulder. However, the utility of EUA as a diagnostic test for patellar instability has not been evaluated. The first purpose of our study was to evaluate the utility of patellar dislocation during EUA as a diagnostic test for assessment of patellar instability. The second purpose of our study was to evaluate demographic and clinical factors associated with the ability to dislocate patella under anesthesia. Methods: A prospective, multicenter cohort study (JUPITER: Justifying Patellar Instability Treatment by Results) database was queried for patients who underwent a surgical intervention for unilateral patellofemoral instability from a period January 2017 through July 2022. All patients had at least one documented patellar dislocation prior to surgery. Demographic and clinical variables were collected including age, sex, BMI, number of dislocations prior to surgery, J-sign and Beighton score. Prior to surgery, all patients underwent EUA in supine position for the involved and the uninvolved knee. During EUA, a submaximal manual force was applied to dislocate the patella laterally with the knee at 0° and 30° flexion. If the patella could be completely dislocated, then the EUA was considered positive. Results were analyzed descriptively, compared between positive and negative EUA cohorts and using multiple logistic regression analysis. Results: 478 patients who underwent unilateral patellar stabilization formed the study cohort. The mean age of the cohort was 15.8 years. 287 were females. 137 patients underwent surgery after the first dislocation, while 340 had surgery for recurrent patellar instability. Mean BMI of the cohort was 24.4. At 0° knee extension, the sensitivity and specificity of EUA as a diagnostic test for patellar instability were 53.4% and 93.3% respectively. The positive and negative predictive values were 90.7% and 61.9% respectively. At 30° knee flexion, the sensitivity and specificity of EUA for diagnosing patellar instability were 37.8% and 96.3%, respectively. The positive and negative predictive values were 92.5% and 55.9% respectively. Compared to negative EUA, the cohort with positive EUA at 0° and 30° was older (p = 0.0312), had more females (p=0.0021), had >5 patellar dislocations (p = 0.0199), had severe J-sign (p = 0.0018) and a higher Beighton score (p = 0.007). There was no difference in BMI between the cohorts. Multiple regression analysis showed that older age and severe J-sign were factors that would increase the odds of positive EUA at 30° knee flexion. There were no factors associated with positive EUA for contralateral knee. Conclusions: About half (53.4%) of all knees with confirmed patellar instability had a dislocatable patella during EUA with knee in extension; this decreased to 37.8% with the knee at 30° flexion. Due to low sensitivity, patellar dislocation during EUA cannot be considered a diagnostic test for patellar instability or a prerequisite for surgical treatment. However, the specificity of 93.3% and 96.3% at 0° and 30°, respectively, suggests that a positive EUA can help to confirm patellar instability.

Objectives: To properly evaluate and quantify how children and adolescents with patello-femoral instability (PFI) perceive their functional status, pain level and QOL, there is great importance in identifying the optimal PROs for this patient population. A few different PRO scales have been commonly used to evaluate individuals with PFI, each designed for a different purpose. The aim of this study was to evaluate the correlation between commonly used Patient Reported Outcome (PRO) scores in assessing children and adolescents with PFI, and to evaluate their sensitivity to change following treatment. Methods: The JUPITER study prospectively collected database was utilized to collect preoperative and 1-year postoperative PRO scores of individuals younger than 19 years of age, who were diagnosed with and treated surgically for Patellofemoral instability (PFI). Patients with a documented episode of patellar dislocation were enrolled in the study by 27 patellofemoral surgeons across 11 institutions in the US, irrespective of treatment approach. All patients completed a set of 4 PROs at the time of enrollment (baseline) and at one-year follow-up using either a paper-based or internet-based data collection sheet. BPII 2.0, IKDC, Kujala and KOOS were assessed. We analyzed the correlation between the four scores, evaluated the sensitivity to change, compared pre- and post-operative scores, and calculated minimal clinical important difference (MCID), and ceiling and floor effects. Results: A total of 1,065 cases were reviewed, and 263 were included (Table 1). The median age of the cohort was 15 (IQR 13 to 16) years, with 177 (67.3%) females. The median BPII 2.0 score was lower than the other three scores at baseline and at 1 year follow up (P<0.001, Table 2). BPII 2.0 presented the most substantial change at 1 year following surgery, increasing by a median 35.96 (IQR 14.9 to 52.35) points. The correlations between the four tested PRO scales are depicted in table 3. BPII 2.0, showed moderate correlation with the other three scores. Among themselves, Kujala, pediatric-IKDC and KOOS had strong correlations (Spearman correlation coefficient > 0.7, P<0.001, Table 3). In the lower 50th percentile baseline score group the change in all PRO scores following surgery was more substantial than in the higher 50th percentile score group (P<0.001). BPII 2.0 was found to be free of a ceiling effect as only 8 (3%) patients scored the maximal 100 points at 1 year follow up. On the contrary, a total of 121 (46%) and 75 (28.5%) patients scored 100 on the 1 year follow up KOOS and Kujala scales, respectively. On the IKDC scale a borderline total count of 40 (15.2%) patients scored 100 points, but 15 (5.7%) additional patients scored 98.91 on this scale, making a total of 20.9% of the patient population at almost the top percentage of the scale. Conclusions: BPII 2.0 score was found to be the most sensitive to change following surgery, and the only scale that did not have a ceiling effect. The moderate correlation between BPII 2.0 and the other three scales emphasizes the limited interchangeability between the scores, that measure different outcome dimensions.