Prospects and challenges of cancer systems medicine: from genes to disease networks.

It is becoming evident that holistic perspectives toward cancer are crucial in deciphering the overwhelming complexity of tumors. Single-layer analysis of genome-wide data has greatly contributed to our understanding of cellular systems and their perturbations. However, fundamental gaps in our knowledge persist and hamper the design of effective interventions. It is becoming more apparent than ever, that cancer should not only be viewed as a disease of the genome but as a disease of the cellular system. Integrative multilayer approaches are emerging as vigorous assets in our endeavors to achieve systemic views on cancer biology. Herein, we provide a comprehensive review of the approaches, methods and technologies that can serve to achieve systemic perspectives of cancer. We start with genome-wide single-layer approaches of omics analyses of cellular systems and move on to multilayer integrative approaches in which in-depth descriptions of proteogenomics and network-based data analysis are provided. Proteogenomics is a remarkable example of how the integration of multiple levels of information can reduce our blind spots and increase the accuracy and reliability of our interpretations and network-based data analysis is a major approach for data interpretation and a robust scaffold for data integration and modeling. Overall, this review aims to increase cross-field awareness of the approaches and challenges regarding the omics-based study of cancer and to facilitate the necessary shift toward holistic approaches.

Assessing the Readability of Clinical Trial Consent Forms for Surgical Specialties.

INTRODUCTION: To evaluate the readability of surgical clinical trial consent forms and compare readability across surgical specialties. METHODS: We conducted a cross-sectional analysis of surgical clinical trial consent forms available on ClinicalTrials.gov to quantitatively evaluate readability, word count, and length variations among different specialties. The analysis was performed between November 2022 and January 2023. A total of 386 surgical clinical trial consent forms across 14 surgical specialties were included. RESULTS: The main outcomes were language complexity (measured using Flesch-Kincaid Grade Level), number of words (measured as word count), time to read (measured at reading speeds of 240 per min), and readability (measured by Flesch Reading Ease Score, Gunning Frog Index, Simple Measures of Gobbledygook Index, FORCAST, and Automated Readability Index). The surgical consent forms were a mean (standard deviation) of 2626 (1668) words long, with a mean of 12:53 min to read at 240 words per min. None of the surgical specialties had an average readability level of sixth grade or lower across all six indices, and only 16 out of 386 (4%) clinical trials met the recommended reading level. Furthermore, there was no significant difference in reading grade level between surgical specialties based on the Flesch-Kincaid Grade Level and Flesch Reading Ease indices. CONCLUSIONS: Our findings suggest that current surgical clinical trial consent documents are too long and complex, exceeding the recommended sixth-grade reading level. Ensuring readable clinical trial consent forms is not only ethically responsible but also crucial for protecting patients' rights and well-being by facilitating informed decision-making.

Defining patient satisfaction after reverse total shoulder arthroplasty: a systematic review.

BACKGROUND: The prevalence of reverse total shoulder arthroplasty (rTSA) has grown rapidly. As indications for the procedure expand, the proportion of patients who have satisfactory outcomes after rTSA has not been well defined. This systematic literature review explores overall patient satisfaction after rTSA and defines patient satisfaction based on indication for surgery. METHODS: A literature search was performed for studies describing patient satisfaction after rTSA in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Papers were included if they investigated patient satisfaction after rTSA at a minimum of 2-year follow-up. Data were collected on patient demographics, including age, gender, and body mass index. Follow-up duration, indication for surgery, and patient reported outcome measures relating to patient satisfaction were also recorded. RESULTS: There were a total of 5234 patients and 5288 shoulders from the 45 included studies. The overall study population was 61.2% female and the average age was 71.1 years (range 23-99). Satisfaction results were recorded at final follow-up, with average follow-up of 49.1 months (range 24-228). Overall patient satisfaction ranged from 77.7% to 87.8%, depending on patient satisfaction patient reported outcome measures. When stratified by diagnosis, patients with a diagnosis of glenohumeral osteoarthritis (GHOA) rated better satisfaction on all metrics when compared to patients with a diagnosis of cuff tear arthropathy or massive rotator cuff tear. CONCLUSION: This systematic review demonstrated that patients who undergo rTSA for either GHOA, cuff tear arthropathy, or massive rotator cuff tear are generally satisfied with their procedure, with the rate of satisfaction highest in GHOA. Focusing on patient satisfaction may provide the best overall assessment of health care quality in a very understandable and tangible form. Overall satisfaction rate is valuable information for patient education and can be utilized as part of effective surgical counseling.

Is Discharge Within a Day Following Total Hip Arthroplasty Safe in the Septuagenarian and Octogenarian Population? A Propensity-Matched Cohort Study.

BACKGROUND: Limited data exists on whether patients older than 70 can safely be discharged within a day (rapid discharge (RD)) following primary total hip arthroplasty (THA). The purpose of this study was to compare perioperative complications and readmission rates associated with RD in patients ≥70 years compared to longer lengths of stay following THA. METHODS: A retrospective, propensity-matched cohort study was conducted using the National Surgical Quality Improvement Program database from 2006 to 2020. Patients ≥70 years undergoing RD following THA were propensity matched to patients ≥70 years who had longer hospital stays (nonrapid discharge). Sub-analyses were performed for septuagenarians and octogenarians. Following 1:1 matching, multivariate analyses were performed to compare perioperative complications and readmissions. Following propensity matching, both groups contained 2,192 patients. RESULTS: The RD patients were found to have shorter operative times (P < .001), less bleeding complications (P < .001), and were more likely to have home discharges (P < .001). The 2 cohorts did not differ in the remaining complications or 30-day postoperative period readmissions among all patients and when evaluating septuagenarians and octogenarians. CONCLUSION: Patients ≥70 years undergoing RD following THA had comparable complication and readmission rates to patients older than 70 undergoing nonrapid discharge. Furthermore, RD patients were more likely to have home discharges and have shorter operations with less bleeding complications. Septuagenarians receiving RD were more likely to have an unplanned readmission. These data suggest that RD following THA can be performed safely in select patients older than 70.

Impact of external beam radiation on total shoulder arthroplasty outcomes: a propensity-matched cohort study.

BACKGROUND: External beam radiation therapy has a number of deleterious effects on the body, and a number of post-operative complications have been reported for several surgeries including total knee arthroplasty. However, few studies have investigated the impact of external beam radiation therapy for total shoulder arthroplasty (TSA). Our study aimed to assess the systemic and joint complications associated with TSA in patients with prior radiation exposures, as well as evaluate the surgical outcomes of radiation patients compared to non-radiation TSA patients. MATERIALS AND METHODS: A retrospective cohort analysis was conducted using the TriNetX Analytics Network. A 1:1 propensity score matching function was utilized to create two cohorts with matched baseline characteristics within the TriNetX network. Comparisons of the primary and secondary outcomes between the two cohorts were made using odds ratios. A p value of < 0.05 was determined to be significant. RESULTS: A total of 75,510 patients that received TSA were identified with 1505 having a history of radiation therapy (RT) and 73,605 with no radiation therapy (non-RT). After propensity matching, both groups contained 1484 patients. RT patients were at higher risk for developing prosthetic joint infection, acute renal failure, altered mental state, cerebrovascular event, DVT, PE, pneumonia, respiratory failure, and UTI compared to non-RT patients at different time points (p < 0.5). CONCLUSION: Patients with prior history of external beam radiation undergoing TSA had a higher risk of systemic complications and prosthetic joint infection compared to patients without a prior history. These complications suggest a more complicated post-operative management course for these patients.

Comparing outcomes in revision total hip arthroplasty in inpatient versus outpatient setting: a matched cohort analysis.

BACKGROUND: As the population ages, revision total hip arthroplasty (rTHA) is becoming more common. However, there is a paucity of literature regarding perioperative outcomes following inpatient versus outpatient rTHA. Our study aims to compare perioperative complications and readmission rates associated with rTHA in a large national cohort. METHODS: A retrospective, propensity-matched cohort study was conducted using the National Surgical Quality Improvement Program database from 2006 to 2020. Patients undergoing rTHA in the inpatient setting were propensity matched to patients receiving rTHA in the outpatient setting. Following 1:1 matching, multivariate analyses were performed to compare perioperative complications and readmission. RESULTS: A total of 207,102 patients were identified, including 181,164 outpatient primary THA, 25,466 inpatient rTHA, and 492 outpatient rTHA patients. Following propensity matching, outpatient primary THA versus outpatient rTHA had 210 patients and inpatient rTHA versus outpatient rTHA had 214 patients. Patients in the outpatient rTHA had a significantly higher operative time (132.4 ± 73.2 versus 90.9 ± 32.7, p < 0.001) and length of stay (1.6 ± 1.6 vs. 0.9 ± 1.0, p < 0.001) compared to outpatient primary THA. When comparing inpatient versus outpatient rTHA, the outpatient cohort had lower operative time (131.1 ± 70.9 vs. 145.4 ± 71.5, p = 0.038), total length of stay (1.7 ± 1.8 vs. 3.6 ± 4.1, p < 0.001), and bleeding complications (6% vs. 18%, p < 0.001). CONCLUSION: There were no difference in the odds of complications between outpatient primary and revision THA. Additionally, rTHA performed in an outpatient setting did not show any increase in immediate compared to inpatient settings. These findings suggest that rTHA can be safely performed on certain patients.

Amygdala subfield and prefrontal cortex abnormalities in patients with functional seizures.

BACKGROUND: Functional seizures (FS) are paroxysmal episodes, resembling epileptic seizures, but without underlying epileptic abnormality. The aetiology and neuroanatomic associations are incompletely understood. Recent brain imaging data indicate cerebral changes, however, without clarifying possible pathophysiology. In the present study, we specifically investigated the neuroanatomic changes in subregions of the amygdala and hippocampus in FS. METHODS: T1 MRI scans of 37 female patients with FS and 37 age-matched female seizure naïve controls (SNC) were analyzed retrospectively in FreeSurfer version 7.1. Seizure naïve controls included patients with depression and anxiety disorders. The analysis included whole-brain cortical thickness, subcortical volumes, and subfields of the amygdala and hippocampus. Group comparisons were carried out using multivariable linear models. RESULTS: The FS and SNC groups did not differ in the whole hippocampus and amygdala volumes. However, patients had a significant reduction of the right lateral amygdala volume (p = 0.00041), an increase of the right central amygdala, (p = 0.037), and thinning of the left superior frontal gyrus (p = 0.024). Additional findings in patients were increased volumes of the right medial amygdala (p = 0.031), left anterior amygdala (p = 0.017), and left dentate gyrus of the hippocampus (p = 0.035). CONCLUSIONS: The observations from the amygdala and hippocampus segmentation affirm that there are neuroanatomic associations of FS. The pattern of these changes aligned with some of the cerebral changes described in chronic stress conditions and depression. The pattern of detected changes further study, and may, after validation, provide biomarkers for diagnosis and treatment.

Is Social Deprivation Associated With Usage, Adverse Events, and Patient-reported Outcome Measures in Total Joint Arthroplasty? A Systematic Review.

BACKGROUND: To capture various social determinants of health, recent analyses have used comprehensive measures of socioeconomic disadvantage such as deprivation and vulnerability indices. Given that studies evaluating the effects of social deprivation on total joint arthroplasty (TJA) have yielded mixed results, a systematic review of this relationship might help answer questions about usage, complications, and results after surgery among patients in different socioeconomic groups and help guide targeted approaches to ensure health equity. QUESTIONS/PURPOSES: We asked: How is social deprivation associated with TJA (1) usage, (2) adverse events including discharge deposition and length of stay, and (3) patient-reported outcome measures (PROMs)? METHODS: A comprehensive review of the PubMed, EBSCO host, Medline, and Google Scholar electronic databases was conducted to identify all studies that evaluated social deprivation and TJA between January 1, 2000, and March 1, 2022. Studies were included if they evaluated comprehensive measures of socioeconomic deprivation rather than individual social determinants of health. Nineteen articles were included in our final analysis with a total of 757,522 patients. In addition to characteristics of included studies (such as patient population, procedure evaluated, and utilized social deprivation metric), we recorded TJA usage, adverse events, and PROM values as reported by each article. Two reviewers independently evaluated the quality of included studies using the Methodological Index for Nonrandomized Studies (MINORS) tool. The mean ± SD MINORS score was 13 ± 1 of 16, with higher scores representing better study quality. All the articles included are noncomparative studies. Given the heterogeneity of the included studies, a meta-analysis was not performed and results were instead presented descriptively. RESULTS: Although there were inconsistencies among the included articles, higher levels of social deprivation were associated with lower TJA usage even after controlling for various confounding variables. Similarly, there was agreement among studies regarding higher proportion of nonhome discharge for patients with more social deprivation. Although there was limited agreement across studies regarding whether patients with more social deprivation had differences in their baseline and postoperative PROMs scores, patients with more social deprivation had lower improvements from baseline for most of the included articles. CONCLUSION: These findings encourage continued efforts focusing on appropriate patient education regarding expectations related to functional improvement and the postoperative recovery process, as well as resources available for further information and social support. We suggest linking patient data to deprivation measures such as the Area Deprivation Index to help encourage shared decision-making strategies that focus on health literacy and common barriers related to access. Given the potential influence social deprivation may have on the outcome and utilization of TJA, hospitals should identify methods to determine patients who are more socially deprived and provide targeted interventions to help patients overcome any social deprivation they are facing. We encourage physicians to maintain close communication with patients whose circumstances include more severe levels of social deprivation to ensure they have access to the appropriate resources. Additionally, as multiple social deprivation metrics are being used in research, future studies should identify a consistent metric to ensure all patients that are socially deprived are reliably identified to receive appropriate treatment. LEVEL OF EVIDENCE: Level III, therapeutic study.

What is the Association Between Clinically Diagnosed Psychiatric Illness and Total Joint Arthroplasty? A Systematic Review Evaluating Outcomes, Healthcare Use, and Patient-reported Outcome Measures.

BACKGROUND: Studies evaluating the effects of a psychiatric illness on orthopaedic surgical outcomes have yielded mixed results. Because awareness of patient comorbid mental health disorders has become increasingly important to tailor treatment plans, the aim of our systematic review was to present the findings of all studies reporting on the association between clinically diagnosed psychiatric illnesses and total joint arthroplasty (TJA) outcomes and evaluate the quality of evidence to provide a comprehensive summary. QUESTION/PURPOSE: Is there a consistently reported association between comorbid psychiatric illness and (1) complication risk, (2) readmission rates, (3) healthcare use and discharge disposition, and (4) patient-reported outcome measures (PROMs) after TJA? METHODS: The PubMed, EBSCO host, Medline, and Google Scholar electronic databases were searched on April 9, 2022, to identify all studies that evaluated outcomes after TJA in patients with a comorbid clinically diagnosed mental health disorder between January 1, 2000, and April 1, 2022. Studies were included if the full-text article was available in English, reported on primary TJA outcomes in patients with clinically diagnosed mental health disorders, included patients undergoing TJA without a psychiatric illness for comparison, and had a minimum follow-up time of 30 days for evaluating readmission rates, 90 days for other perioperative outcomes such as length of stay and complications, and 1-year minimum follow-up if assessing PROMs. Studies that used a mental health screening examination instead of clinical diagnoses were excluded to isolate for verified psychiatric illnesses. Additionally, systematic reviews, case reports, duplicate studies between the databases, and gray literature were excluded. Twenty-one studies were included in our final analysis comprising 31,023,713 patients with a mean age range of 57 to 69 years. Mental health diagnoses included depression, anxiety, bipolar disorder, schizophrenia, major personality disorder, and psychosis as well as concomitant mental disorders. Two reviewers independently evaluated the quality of included studies using the Methodological Index for Nonrandomized Studies (MINORS) tool. The mean MINORS score was 19.5 ± 0.91 of 24, with higher scores representing better study quality. All the articles included were retrospective, comparative studies. Given the heterogeneity of the included studies, a meta-analysis was not performed, and results are instead presented descriptively. RESULTS: Patients with schizophrenia were consistently reported to have higher odds of medical and surgical complications than patients without psychiatric illness, particularly anemia and respiratory complications. Among studies with the largest sample sizes, patients with depression alone or depression and anxiety had slightly higher odds of complications. Most studies identified higher odds of readmission among patients with depression, schizophrenia, and severe mental illness after TJA. However, for anxiety, there was no difference in readmission rates compared with patients without psychiatric illness. Slightly higher odds of emergency department visits were reported for patients with depression, anxiety, concomitant depression and anxiety, and severe mental illness across studies. When evaluating healthcare use, articles with the largest sample sizes reporting on depression and length of stay or discharge disposition found modestly longer length of stay and greater odds of nonhome discharge among patients with depression. Although several studies reported anxiety was associated with slightly increased total costs of hospitalization, the most robust studies reported no difference or slightly shorter average length of stay. However, the included studies only reported partial economic analyses of cost, leading to relatively superficial evidence. Patients with schizophrenia had a slightly longer length of stay and modestly lower odds of home discharge and cost. Likewise, patients with concomitant depression and anxiety had a slightly longer average length of stay, according to the two articles reporting on more than 1000 patients. Lastly, PROM scores were worse in patients with depression at a minimum follow-up of 1 year after TJA. For anxiety, there was no difference in improvement compared with patients without mental illness. CONCLUSION: Our systematic review found that individuals with psychiatric illness had an increased risk of postoperative complications, increased length of stay, higher costs, less frequent home discharge, and worse PROM scores after TJA. These findings encourage inclusion of comorbid psychiatric illness when risk-stratifying patients. Attention should focus on perioperative interventions to minimize the risk of thromboembolic events, anemia, bleeding, and respiratory complications as well as adequate pain management with drugs that do not exacerbate the likelihood of these adverse events to minimize emergency department visits and readmissions. Future studies are needed to compare patients with concomitant psychiatric illnesses such as depression and anxiety with patients with either diagnosis in isolation, instead of only comparing patients with concomitant diagnoses with patients without any psychiatric illnesses. Similarly, the results of targeted interventions such as cognitive behavioral therapy are needed to understand how orthopaedic surgeons might improve the quality of care for patients with a comorbid psychiatric illness.

What Are the Trends in Research Publication Misrepresentation Among Orthopaedic Residency and Fellowship Applicants From 1996 to 2019? A Systematic Review.

BACKGROUND: Because research experience is increasingly important in ranking orthopaedic residency and fellowship applicants, determining the accuracy of candidates reporting their scholarly activity is essential. However, disparate and inconsistent findings have made it difficult to draw meaningful conclusions from individual studies. QUESTIONS/PURPOSES: In this systematic review, we asked: (1) What percentage of research publications are misrepresented among orthopaedic residency and fellowship applicants? (2) What percentage of applications contain one or more example of academic misrepresentation? (3) Is research misrepresentation associated with any individual applicant characteristics? (4) What is the publication status of articles listed by applicants as having been submitted to journals? METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed, EBSCOhost, Medline, and Google Scholar electronic databases were searched on March 10, 2022, to identify all studies that evaluated research misrepresentation in orthopaedic residency and fellowship applications between January 1, 1995, and March 1, 2022. Articles were included if full-text articles in English were available and the study reported on research misrepresentation among orthopaedic residency or fellowship applicants. Studies investigating nonorthopaedic publications, systematic reviews, case studies, duplicate studies among databases, and gray literature were excluded. Two reviewers independently evaluated the quality of included studies using the Methodological Index for Nonrandomized Studies (MINORS) tool. This is a validated assessment tool that grades noncomparative studies from 0 to 16 and studies with control groups from 0 to 24, based on eight criteria related to study design, outcomes assessed, and follow-up. All included articles were noncomparative studies, so the maximum score here was 16, with higher scores indicating better study quality. The mean MINORS score was 13 ± 1 in the studies we included. The final analysis included 10 studies with 5119 applicants. Eight studies evaluated orthopaedic residency applicants and two evaluated fellowship applicants. The applicant classes ranged from 1996 to 2019. Research misrepresentation was defined among studies as nonauthorship of an existing article, claimed authorship of a nonexistent article, or incorrect listing of authorship order for an existing article. Each study's findings and definition of research misrepresentation were considered to allow for a discussion of overall trends. The percentage of misrepresentation was further broken down by the misrepresentation type. Applicant characteristics and destination of submitted articles were also evaluated. Given the potential overlap between applicants among the studies, no pooled analysis was conducted, and results are presented as a narrative summary. RESULTS: The percentage of overall publication misrepresentation was estimated to range between 1% (13 of 1100) and 21% (27 of 131), with more-recent studies reporting a lower proportion of overall articles misrepresented. Most studies we found claimed that authorship of a nonexistent article was the most common type of misrepresentation. Nonauthorship of an existing article and incorrect authorship order were less common. The percentage of applications with at least one misrepresentation was approximately 20% between 1998 and 2017. Most studies found no applicant characteristics, such as match outcomes, demographic markers, or academic records, that were consistently associated with a higher odds of the candidate misrepresenting his or her research credentials. Finally, approximately half of the articles listed as submitted to journals went on to publication, with one-third going to a different journal with a lower Impact Factor. CONCLUSIONS: Our systematic review found that the percentage of overall publication misrepresentations among orthopaedic residency and fellowship applicants has generally been low over the past 20 years. However, approximately one-fifth of applications had at least one research misrepresentation, with 2% having multiple misrepresentations on reported publications. There were no consistent applicant characteristics associated with higher odds of research misrepresentation. Additionally, most of the articles listed as submitted to journals for publication were ultimately published. CLINICAL RELEVANCE: Although the decrease in overall publication misrepresentation is encouraging, our finding that one-fifth of applicants have research misrepresentation is a cause for concern. In light of a continually evolving application process, orthopaedic residency and fellowship programs must ensure there is integrity related to information that is self-reported by applicants. These findings also serve to encourage faculty members involved in the application screening and decision process to limit biases related to applicant demographics perceived to be associated with a high odds of misrepresentation. Furthermore, governing agencies and program leadership should evaluate methods of verifying unpublished work and provide opportunities for applicants to give publication updates throughout the application cycle.

What Are the Trends in Women's Representation Among Lead Investigators of Orthopaedic Clinical Trials?

BACKGROUND: Serving as a principal investigator for a clinical trial can bring national visibility and recognition to physicians, and it can have a substantial impact on their promotion and tenure. In the field of orthopaedics, there is a well-known gender gap in terms of representation and leadership. Examining the representation of women in clinical trial leadership may help to inform and enable the design of targeted interventions and policies to foster a more inclusive and diverse environment in clinical trial leadership. QUESTIONS/PURPOSES: (1) What is the proportion of women principal investigators in orthopaedic clinical trials, and has this changed over time? (2) Are there trial characteristics (trial phase, status, funding source, and intervention) associated with women principal investigators? (3) What is the geographic distribution globally and regionally within the United States of clinical trials led by women principal investigators? METHODS: A cross-sectional survey of clinical trials using the ClinialTrials.gov registry and results database provided by the NIH was performed on August 22, 2022. Trial characteristics included principal investigator names and gender, trial phase, type, funding source, intervention, and location (defined by continent and US Census region). Our primary outcome was the overall proportion of women orthopaedic principal investigators over time. We assessed this by comparing the proportion of women principal investigators from 2007 to 2022. Our secondary outcomes were trial characteristics (trial phase, status, funding source, and intervention) and geographic distribution (globally and within the United States) associated with women principal investigators. Baseline characteristics of the clinical trials were calculated using frequencies and percentages for categorical variables. Fisher exact tests were conducted to evaluate differences in gender proportions based on the included clinical trial characteristics. Univariate linear regression was applied to analyze trends in the annual proportion of women principal investigators over time. RESULTS: The overall proportion of women principal investigators was 18% (592 of 3246), and this proportion increased over the study period. Specifically, the proportion of women leading clinical trials was 13% (16 of 121) in 2007 and 22% (53 of 242) in 2022 (r2 = 0.68; p < 0.001). This trend was also observed when evaluating only US women principal investigators (r2 = 0.47; p = 0.003) and non-US women principal investigators over the study period (r2 = 0.298; p = 0.03). There was no difference in the distribution of trial phases between men and women principal investigators. Most men and women were involved in "not applicable" or Phase IV trials. Similarly, there was no difference in trial status or funding source. However, women principal investigators had a higher proportion of studies involving behavioral interventions (11% [67 of 592]) compared with men principal investigators (3% [74 of 2654]; p = 0.03). The proportion of women principal investigators over the study period by world region revealed a higher proportion of women principal investigators in Asia (23% [88 of 391]), followed by South America (24% [12 of 49]), North America (18% [306 of 1746]), and Europe (16% [136 of 833]). Among all US trials over the study period, the proportion of women principal investigators across the US Census region was Northeast (19% [62 of 329]), South (18% [90 of 488]), West (20% [97 of 492]), and Midwest (13% [22 of 168]). CONCLUSION: Although there has been a notable increase in the proportion of women principal investigators over time, the overall representation remains relatively low. The disparities observed in trial characteristics and geographic distribution of women principal investigators further emphasize the need for targeted interventions and policies to foster a more inclusive and diverse environment in clinical trial leadership. CLINICAL RELEVANCE: These results underscore the importance of adopting practices and strategies that foster gender equity in the leadership of orthopaedic clinical trials. By establishing mentorship and sponsorship programs, early-career women surgeons can be connected with experienced leaders, cultivating a supportive network and offering valuable career guidance. Additionally, addressing geographic disparities in the representation of women principal investigators can involve the implementation of mentorship and sponsorship programs in regions with lower representation.

Asymptomatic Bone Marrow Edema in Weight-bearing Bones in Athletes and Military Trainees: A Systematic Literature Review.

Asymptomatic bone marrow edema (aBME) is a non-specific radiographic finding often found in athletes. Although aBME may represent the body's physiological response to training load, the etiology, MRI characteristics, and natural history of aBME remain unknown. To better characterize aBME in the lower extremities of military trainees and athletes. A systematic literature review in accordance with PRISMA guidelines was performed to identify primary research articles reporting on aBME in the lower extremities of athletes and military trainees. We identified 347 unique articles and after applying inclusion and exclusion criteria, 10 articles were included for qualitative synthesis. There were a total of 444 patients with an average age of 28.4±9.6 included. The most commonly used MRI sequences were proton-density with fat-saturation and T1-weighted imaging. The pattern of BME was inconsistently described, with various classification schemas used. The changes in aBME during longitudinal follow-up were dynamic and demonstrated both radiographic progression and regression. aBME is a highly prevalent and radiographically dynamic entity observed in high-level athletes and military trainees. Although follow-up was limited in the included studies, aBME may represent a natural, non-pathologic, reaction in response to specific biomechanical stressors.

Complications in Osteonecrosis Patients Following Total Knee Arthroplasty: A Propensity-Matched Cohort Study.

BACKGROUND: Several studies have demonstrated high complication rates in osteonecrosis (ON) patients undergoing total hip arthroplasty. However, there is a paucity of literature regarding outcomes of total knee arthroplasty (TKA) in ON patients. Our study aimed to assess preoperative risk factors associated with the development of ON and determine the incidence of postoperative complications up to one year following TKA. METHODS: A retrospective cohort study was conducted using a large national database. Patients who had a primary TKA and ON were isolated using Current Procedural Terminology code 27447 and ICD-10-CM code M87, respectively. A total of 185,045 patients were identified, including 181,151 patients who had a TKA and 3,894 patients who had a TKA and ON. After propensity matching, both groups each contained 3,758 patients. Intercohort comparisons of primary and secondary outcomes after propensity score matching were made using the odds ratio. A P value of < .01 was determined to be significant. RESULTS: The ON patients were found to have an increased risk for prosthetic joint infection, urinary tract infection, deep vein thrombosis, pulmonary embolism, wound dehiscence pneumonia, and the development of heterotopic ossification at different time points. Osteonecrosis patients had an increased risk of revision at the 1-year time point (odds ratio = 2.068, P < .0001). CONCLUSION: The ON patients had a higher risk of systemic and joint complications than non-ON patients. These complications suggest a more complicated management course for patients who have ON prior to and after TKA.

Readability of Online Patient Education Materials for Total Joint Arthroplasty: A Systematic Review.

BACKGROUND: As the demand for total joint arthroplasty continues to grow, patients increasingly turn to internet sources for accessible orthopaedic health information. We sought to evaluate the readability of online hip and knee arthroplasty patient education materials (PEMs). METHODS: Our systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P guidelines (PROSPERO registration of the study protocol: CRD42022358872, September 19th, 2022). PubMed, EBSCOhost, Medline, and Google Scholar electronic databases were utilized to identify all studies evaluating online PEMs related to total joint arthroplasty between January 1, 2000, and August 1, 2022. The quality of studies was assessed with the Joanna Briggs Institute scale. RESULTS: Our initial search yielded 360 publications which were then screened for appropriate studies aligned with our review's purpose. A total of eleven cross-sectional studies were included. The total sample size across the studies consisted of 662 PEMs. Five studies evaluated professional or academic orthopaedic websites, six evaluated PEMs through web engines, and three evaluated apps or commercial websites. Most included studies found PEMs to be well above the recommended 6th-grade reading level. CONCLUSION: Arthroplasty PEMs produced by orthopaaedic websites, web searches, and apps have readability scores well above the recommended levels. Given the importance of health literacy on patient outcomes and satisfaction, work needs to be done to improve the readability of these materials.

Effects of ginger (Zingiber officinale) supplementation on testicular histology, semen characteristic, blood plasma parameters and reproductive performance in aged broiler breeder roosters.

Higher long-chain polyunsaturated fatty acids contents in roosters' sperm plasma membrane along with age-related decrease in antioxidant defense make the spermatozoa very susceptible to lipid peroxidation. Ginger root contains abundant amounts of gingerol, shogaols, gingerdiol and other active compounds, which known as antioxidant compounds to enhance semen quality. The goal of the study was to evaluate the effect of dietary supplementation of ginger root on semen quality, blood chemistry, immune response, testicular histology and reproductive performance of Ross-308 breeder roosters from 47 to 60 weeks of age. The feeding of ginger root resulted in an increase in parameters related to sperm forward motility and seminal total antioxidant capacity (TAC), and following there was a tendency to increase and decrease in seminal superoxide dismutase activity and malondialdehyde concentration, respectively; however, sperm concentration was not affected. There was an increase and tendency to increase in blood total protein and TAC in the supplemented group respectively. The roosters fed ginger supplemented diet had a higher spermiation index; and following there was tendency to increase seminal tubes spermatozoids number (p = 0.056) and repopulation index (p = 0.058). Despite the improved seminal antioxidant status and a tendency to lower embryonic mortality in the ginger-received group, the fertility and hatchability rate of roosters were statistically insignificant. Supplementations of ginger root in ageing rooster's diet had a beneficial effect on sperm motility, seminal antioxidant status and testicular spermiation index.

Traces of JC polyomavirus in papillary thyroid cancer: a comprehensive study in Iran.

BACKGROUND: JC polyomavirus (JCPyV) is known to induce solid tumors such as astrocytomas, glioblastomas, and neuroblastomas in experimental animals, and recent studies have shown that the virus may be correlated with carcinogenesis. This study aimed to evaluate the impact of JCPyV on the progression of papillary thyroid cancer (PTC). METHODS: A total of 1057 samples, including 645 paraffin-embedded PTC biopsy samples (PEBS) and 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples were evaluated for the presence of JCPyV DNA and RNA. RESULTS: We observed that 10.8% (114/1057) samples, including 17.5% (72/412) FBS and 6.5% (42/645) PEBS were positive for the JCPyV DNA. Among the JCPyV-positive samples, the mean JCPyV copy number was lower in patients with PEBS (0.3 × 10-4 ± 0.1 × 10-4 copies/cell) compared to FBS (1.8 × 10-1 ± 0.4 × 10-1 copies/cell) and non-PTC normal samples (0.2 × 10-5 ± 0.01 × 10-5 copies/cell), with a statistically significant difference (P < 0.001). The LT-Ag RNA expression was lower in PEBS than in FBS, while no VP1 gene transcript expression was found. CONCLUSIONS: Although our results confirmed the presence of JCPyV in some Iranian patients with PTC, more research is needed to verify these results.

Clinical MRI morphological analysis of functional seizures compared to seizure-naïve and psychiatric controls.

PURPOSE: Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS and clinically relevant comparison populations. METHODS: Quality-screened clinical-grade MRIs were acquired from 666 patients from 2006 to 2020. Morphometric features were quantified with FreeSurfer v6. Mixed-effects linear regression compared the volume, thickness, and surface area within 201 regions-of-interest for 90 patients with FS, compared to seizure-naïve patients with depression (n = 243), anxiety (n = 68), and obsessive-compulsive disorder (OCD, n = 41), respectively, and to other seizure-naïve controls with similar quality MRIs, accounting for the influence of multiple confounds including depression and anxiety based on chart review. These comparison populations were obtained through review of clinical records plus research studies obtained on similar scanners. RESULTS: After Bonferroni-Holm correction, patients with FS compared with seizure-naïve controls exhibited thinner bilateral superior temporal cortex (left 0.053 mm, p = 0.014; right 0.071 mm, p = 0.00006), thicker left lateral occipital cortex (0.052 mm, p = 0.0035), and greater left cerebellar white-matter volume (1085 mm3, p = 0.0065). These findings were not accounted for by lower MRI quality in patients with FS. CONCLUSIONS: These results reinforce prior indications of structural neuroimaging correlates of FS and, in particular, distinguish brain morphology in FS from that in depression, anxiety, and OCD. Future work may entail comparisons with other psychiatric disorders including bipolar and schizophrenia, as well as exploration of brain structural heterogeneity within FS.

Preconditioning of bull semen with sub-lethal oxidative stress before cryopreservation: Possible mechanism of mitochondrial uncoupling protein 2.

Preconditioning of sperm using sub-lethal oxidative stress before cryopreservation is an innovative approach that can improve sperm cryo-survival. Mitochondrial uncoupling proteins (UCPs) are critical in reducing ROS level during stress conditions. The aim of the current study was to investigate whether mild sub-lethal stress induced by low concentrations of nitric oxide and hydrogen peroxide has a protective effect on quality parameters of post-thaw bull semen through modulations of mitochondrial uncoupling protein 2 (UCP2) expression. Semen samples were collected from 6 mature Holstein bulls, then mixed and divided into 8 aliquots: fresh, frozen control and frozen groups treated with NO: 0.1 (NO-0.1), 1(NO-1), 10 µM (NO-10), and H2O2: 0.1(H2O2-0.1), 1(H2O2-1) and 10µM (H2O2-10). A significantly higher percentage of total motility, progressive motility and viability was observed in NO-1 and H2O2-10 compared to the other frozen groups (P < 0.05). Sperm exposed to 1 µM NO and 10µM H2O2 showed significantly increased percentages of mitochondria activity and membrane integrity (P < 0.05). Moreover, the lowest percentage of apoptotic percentage was observed in the NO-1 and H2O2-10 in comparison to the other frozen groups. In addition, the expression level of UCP2 was higher in the NO-1 and H2O2-10 compared to the other groups (P < 0.05). It can be concluded that stress preconditioning of bull sperm before cryopreservation can increase UCP2 expression of sperm, that can play a protective role against cryoinjury after thawing.

Reliability of additional reported seizure manifestations to identify dissociative seizures.

PURPOSE: Descriptions of seizure manifestations (SM), or semiology, can help localize the symptomatogenic zone and subsequently included brain regions involved in epileptic seizures, as well as identify patients with dissociative seizures (DS). Patients and witnesses are not trained observers, so these descriptions may vary from expert review of seizure video recordings of seizures. To better understand how reported factors can help identify patients with DS or epileptic seizures (ES), we evaluated the associations between more than 30 SMs and diagnosis using standardized interviews. METHODS: Based on patient- and observer-reported data from 490 patients with diagnoses documented by video-electoencephalography, we compared the rate of each SM in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic seizure-like events (PSLE), mixed DS and ES, and inconclusive testing. RESULTS: In addition to SMs that we described in a prior manuscript, the following were associated with DS: light triggers, emotional stress trigger, pre-ictal and post-ictal headache, post-ictal muscle soreness, and ictal sensory symptoms. The following were associated with ES: triggered by missing medication, aura of déjà vu, and leftward eye deviation. There were numerous manifestations separately associated with mixed ES and DS. CONCLUSIONS: Reported SM can help identify patients with DS, but no manifestation is pathognomonic for either ES or DS. Patients with mixed ES and DS reported factors divergent from both ES-alone and DS-alone.

Objective score from initial interview identifies patients with probable dissociative seizures.

OBJECTIVE: To develop a Dissociative Seizures Likelihood Score (DSLS), which is a comprehensive, evidence-based tool using information available during the first outpatient visit to identify patients with "probable" dissociative seizures (DS) to allow early triage to more extensive diagnostic assessment. METHODS: Based on data from 1616 patients with video-electroencephalography (vEEG) confirmed diagnoses, we compared the clinical history from a single neurology interview of patients in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic nonepileptic seizure-like events (PSLE), mixed DS plus ES, and inconclusive monitoring. We used data-driven methods to determine the diagnostic utility of 76 features from retrospective chart review and applied this model to prospective interviews. RESULTS: The DSLS using recursive feature elimination (RFE) correctly identified 77% (95% confidence interval (CI), 74-80%) of prospective patients with either ES or DS, with a sensitivity of 74% and specificity of 84%. This accuracy was not significantly inferior than neurologists' impression (84%, 95% CI: 80-88%) and the kappa between neurologists' and the DSLS was 21% (95% CI: 1-41%). Only 3% of patients with DS were missed by both the fellows and our score (95% CI 0-11%). SIGNIFICANCE: The evidence-based DSLS establishes one method to reliably identify some patients with probable DS using clinical history. The DSLS supports and does not replace clinical decision making. While not all patients with DS can be identified by clinical history alone, these methods combined with clinical judgement could be used to identify patients who warrant further diagnostic assessment at a comprehensive epilepsy center.