Therapeutic radiation directly alters bone fatigue strength and microdamage accumulation.

Radiotherapy (RTx) is an essential and efficacious oncologic treatment, however, post-RTx bone fragility fractures present a challenging clinical problem. Cancer survivors treated with RTx are at variable risk for these late-onset, complex fragility fractures. Little data exists regarding the effects of RTx on bone fatigue properties despite the likelihood of fatigue loading as a mechanism leading up to atraumatic fracture. In this study, femurs collected from adult male rats were irradiated ex vivo with a therapeutic dose of x-irradiation (20 Gy), and then fatigued using a three-point bend setup. Femurs positioned in an isotonic bath at room temperature were loaded to a range of prescribed initial strain levels (based on beam theory equations, prior to any fatigue damage) at 3 Hz in force control. The goals of this study were to determine the feasibility of assessing RTx-induced alterations in 1) femur fatigue strength, 2) structural microdamage (creep and stiffness), and 3) tissue damage (diffuse damage and/or linear microcracking). Mid-diaphyseal morphology and tissue mineral density were not different between the RTx and Sham groups (p ≥ 0.35). With increasing applied apparent strain, the number of cycles to failure was reduced for the RTx femurs when compared to the Sham femurs (treatment x εapp, p = 0.041). RTx femurs had a greater phase II (steady state) creep rate (p = 0.0462) compared to Sham femurs. For femurs that reached 500k cycles, the RTx group had greater diffuse damage area (p = 0.015) than the Sham. This study provides evidence that radiation at therapeutic doses can directly diminish bone fatigue properties. This loss of fatigue properties is associated with increased structural fatigue damage and diffuse microdamage, without alterations in morphology or tissue mineral density, indicating a reduction in bone quality.

Tuberculosis Peritonitis Resulting in Small Bowel Obstruction.

Tuberculosis (TB) peritonitis resulting in a small bowel obstruction is uncommon and can be a challenging infectious disease to diagnose. It often has an insidious onset with non-specific symptoms. Today we report a rare case of a 30-year-old woman who recently traveled to Vietnam and presented with worsening upper and lower gastrointestinal symptoms. CT scan revealed an ill-defined mass in the terminal ileum with prominent mucosal enhancement and wall thickening, which ultimately led to subsequent colonoscopy and Quantiferon Gold testing, revealing a positive result. Biopsy of the mass demonstrated noncaseating granulomatous colitis with rare acid-fast positive bacillus consistent with mycobacterial infection. As a result, the patient was ultimately initiated on antituberculosis therapy. Shortly thereafter, she was readmitted with clinical features suggestive of a bowel obstruction. The patient was managed with supportive care and did not require surgical intervention. However, approximately two months following the readmission, she presented to the emergency department once again with a mechanical bowel obstruction that ultimately required surgery. This case underscores the importance of TB testing in patients with insidious, worsening gastrointestinal symptoms and highlights the potential complications of TB peritonitis, even in those undergoing antituberculosis treatment.

Pickleball and the Rising Incidence of Achilles Tendon Injuries in the Elderly.

BACKGROUND: With its rising popularity of pickleball, particularly in the aging population, comes concern for potential injuries that previously rarely affected this patient cohort. The purpose of this study was to investigate the trends of pickleball-related Achilles tendon injuries. METHODS: A retrospective case series was performed to determine the trends associated with pickleball-related Achilles tendon injuries over the last 10 years. A database search of all Achilles tendon ruptures (ICD-10 S86.0) presenting to a large, multistate, subspecialty referral orthopaedic clinic between January 2013 and June 2023 were identified and included in the study. Pickleball-related injuries were identified via query and confirmed with manual chart review. The incidence of pickleball-related injuries, as well as patient demographics and rate of surgery was determined and compared with the total population during that time period. RESULTS: A total of 2684 patients who suffered an Achilles tendon injury between January 2013 and June 2023 were identified, with 43 patients meeting the inclusion criteria for pickleball-related Achilles tendon ruptures. The number and overall incidence of pickleball-related Achilles tendon injuries has been increasing since 2016, excluding 2020 where there was a large decrease likely due to the COVID-19 epidemic. Pickleball was associated with older age at time of injury (64.5 vs 48.6, P < .001) as well as a lower BMI (26.6 vs 29.4, P < .001). In addition, patients who sustained a pickleball-related Achilles tendon injury were more likely to undergo surgery (67.4% vs 45.4%, P = .008). CONCLUSION: The rising popularity of pickleball and its associated injuries poses a significant risk to the aging population, with Achilles tendon injuries occurring in older individuals and resulting in a higher likelihood of undergoing surgery. LEVEL OF EVIDENCE: IV; retrospective case-series.

Multiligament knee injury (MLKI): an expert consensus statement on nomenclature, diagnosis, treatment and rehabilitation.

Multiligament knee injuries (MLKIs) represent a broad spectrum of pathology with potentially devastating consequences. Currently, disagreement in the terminology, diagnosis and treatment of these injuries limits clinical care and research. This study aimed to develop consensus on the nomenclature, diagnosis, treatment and rehabilitation strategies for patients with MLKI, while identifying important research priorities for further study. An international consensus process was conducted using validated Delphi methodology in line with British Journal of Sports Medicine guidelines. A multidisciplinary panel of 39 members from 14 countries, completed 3 rounds of online surveys exploring aspects of nomenclature, diagnosis, treatment, rehabilitation and future research priorities. Levels of agreement (LoA) with each statement were rated anonymously on a 5-point Likert scale, with experts encouraged to suggest modifications or additional statements. LoA for consensus in the final round were defined 'a priori' if >75% of respondents agreed and fewer than 10% disagreed, and dissenting viewpoints were recorded and discussed. After three Delphi rounds, 50 items (92.6%) reached consensus. Key statements that reached consensus within nomenclature included a clear definition for MLKI (LoA 97.4%) and the need for an updated MLKI classification system that classifies injury mechanism, extent of non-ligamentous structures injured and the presence or absence of dislocation. Within diagnosis, consensus was reached that there should be a low threshold for assessment with CT angiography for MLKI within a high-energy context and for certain injury patterns including bicruciate and PLC injuries (LoA 89.7%). The value of stress radiography or intraoperative fluoroscopy also reached consensus (LoA 89.7%). Within treatment, it was generally agreed that existing literature generally favours operative management of MLKI, particularly for young patients (LoA 100%), and that single-stage surgery should be performed whenever possible (LoA 92.3%). This consensus statement will facilitate clinical communication in MLKI, the care of these patients and future research within MLKI.

Combined tibial deflexion osteotomy and anterior cruciate ligament reconstruction improves knee function and stability: A systematic review.

IMPORTANCE: Patients with excessive posterior tibial slope (PTS) may have higher risks of anterior cruciate ligament (ACL) reconstruction (ACL-R) failure, and clinical outcomes after revision of ACL-R procedures are typically poor. OBJECTIVE: This study aimed to perform a systematic review of the literature summarizing the clinical and radiological outcomes of the surgical treatment of ACL insufficiency in the setting of excessive PTS using a tibial deflexion osteotomy combined with ACL-R. EVIDENCE REVIEW: A systematic review of the literature was performed using PubMed, Cochrane Library, and OVID Medline databases from 1990 to present. Inclusion criteria were studies of outcomes of isolated tibial deflexion osteotomies performed with primary or revision ACL-R in the English language. Data extracted included study demographic information, type of tibial deflexion osteotomy and concomitant procedures, radiological outcomes, patient-reported outcome scores, and postoperative complications. FINDINGS: Six studies, with 133 knees were identified. All included studies were retrospective case series, with a weighted mean follow-up of 3.39 years. In 106 of 133 (79.7%) knees, tibial deflexion osteotomy was performed concomitantly with an ACL-R, whereas in 27 of 133 (20.3%) knees, the procedures were staged. 22, 45, and 66 of 133 knees (16.5%, 33.8%, and 49.6%) underwent primary, first revision, and second or greater revision ACL-R, respectively. Three of 133 (2.25%) knees demonstrated recurrent ACL graft failure at the final follow-up. On average, PTS decreased from 15.2° preoperatively to 7.1° postoperatively. The mean International Knee Documentation Committee, Lysholm, and Tegner scores increased from 42.5, 46.4, and 4.2 preoperatively to 71.8, 89.0, and 6.7 postoperatively. CONCLUSIONS: The results of this review suggest that combined ACL-R and tibial deflexion osteotomy may be effective in decreasing PTS and improving knee function and stability. STUDY DESIGN: Systematic Review; Level of evidence 4.

More People, More Active, More Often for Heart Health - Taking Action on Physical Activity.

Physical inactivity is a leading contributor to increased cardiovascular morbidity and mortality. Almost 500 million new cases of preventable noncommunicable diseases (NCDs) will occur globally between 2020 and 2030 due to physical inactivity, costing just over US$300 billion, or around US$ 27 billion annually (WHO 2022). Active adults can achieve a reduction of up to 35% in risk of death from cardiovascular disease. Physical activity also helps in moderating cardiovascular disease risk factors such as high blood pressure, unhealthy weight and type 2 diabetes. For people with cardiovascular disease, hypertension, type 2 diabetes and many cancers, physical activity is an established and evidence-based part of treatment and management. For children and young people, physical activity affords important health benefits. Physical activity can also achieve important cross-sector goals. Increased walking and cycling can reduce journeys by vehicles, air pollution, and traffic congestion and contribute to increased safety and liveability in cities.

NCI Resources for Cancer Immunoprevention Research.

Cancer prevention and early detection, the first two of the eight primary goals of the National Cancer Plan released in April 2023, are at the forefront of the nation's strategic efforts to reduce cancer incidence and mortality. The Division of Cancer Prevention (DCP) of the NCI is the federal government's principal component devoted to promoting and supporting innovative cancer prevention research. Recent advances in tumor immunology, cancer immunotherapy, and vaccinology strongly suggest that the host immune system can be effectively harnessed to elicit protective immunity against the development of cancer, that is, cancer immunoprevention. Cancer immunoprevention may be most effective if the intervention is given before or early in the carcinogenic process while the immune system remains relatively uncompromised. DCP has increased the emphasis on immunoprevention research in recent years and continues to expand program resources and interagency collaborations designed to facilitate research in the immunoprevention field. These resources support a wide array of basic, translational, and clinical research activities, including discovery, development, and validation of biomarkers for cancer risk assessment and early detection (Early Detection Research Network), elucidation of biological and pathophysiological mechanistic determinants of precancer growth and its control (Translational and Basic Science Research in Early Lesions), spatiotemporal multiomics characterization of precancerous lesions (Human Tumor Atlas Network/Pre-Cancer Atlas), discovery of immunoprevention pathways and immune targets (Cancer Immunoprevention Network), and preclinical and clinical development of novel agents for immunoprevention and interception (Cancer Prevention-Interception Targeted Agent Discovery Program, PREVENT Cancer Preclinical Drug Development Program, and Cancer Prevention Clinical Trials Network).

Editorial Commentary: Two-Year Follow-Up Is Too Short to Determine the Effectiveness of Anterior Cruciate Ligament Primary Repair.

Although recent studies have shown good results of anterior cruciate ligament primary repair at 2-year follow-up, one must be careful in adopting this technique. Historically, the classic study from West Point showed repair fails at 5 years. Perhaps future results will be improved with scaffolds, augmentation, or biologics. Only time will tell. For now, what's the (West) Point?

Surfing uncertainty with screams: predictive processing, error dynamics and horror films.

Despite tremendous efforts in psychology, neuroscience and media and cultural studies, it is still something of a mystery why humans are attracted to fictional content that is horrifying, disgusting or otherwise aversive. While the psychological benefits of horror films, stories, video games, etc. has recently been demonstrated empirically, current theories emphasizing the negative and positive consequences of this engagement often contradict one another. Here, we suggest the predictive processing framework may provide a unifying account of horror content engagement that provides clear and testable hypotheses, and explains why a 'sweet spot' of fear and fun exists in horror entertainment. This article is part of the theme issue 'Art, aesthetics and predictive processing: theoretical and empirical perspectives'.

Relative contributions of the supraspinatus cord and strap tendons to shoulder abduction and translation.

BACKGROUND: The supraspinatus (SS) is formed by a larger anterior bipennate muscle with a cord-like tendon and a posterior unipennate muscle with a strap-like tendon. There is a tendinous connection between the 2 SS subunits. Yet, the relative mechanical contribution of the SS cord and SS strap musculotendinous units to load transmission and subsequent shoulder abduction force is unknown. We hypothesized that a simulated SS cord vs. an SS strap tear would generate less shoulder abduction force and, further, an intact SS cord would offset the expected abduction loss from an SS strap tear, but the inverse would not be true. MATERIALS AND METHODS: Twenty fresh-frozen cadaveric specimens were tested in a shoulder simulator with physiological load vectors applied to the upper and lower subscapularis, SS cord, SS strap, infraspinatus, and teres minor. The roles of the SS cord and SS strap muscles were delineated by varying their loads, while keeping constant loads on other muscles. The randomized testing trials included a native condition and 4 test cases that simulated tears by dropping the load and force transfer via the SS cord-to-SS strap connection by adding the load. Testing was completed at both 0° and 30° of abduction. During each test, shoulder abduction force, rotator cuff strains, and humeral translation were measured. RESULTS: Simulated isolated SS cord and SS strap tears led to a significantly lower shoulder abduction force (P < .001). A simulated cord tear at 0° and 30° reduced the abduction force by 53% and 38%, respectively. A simulated strap tear at 0° and 30° dropped the abduction force by 27% and 23%, respectively. The decline in the abduction force was larger for the SS cord tear vs. SS strap tear (P ≤ .001). An SS cord tear with full-load transfer to the strap was able to recover to native values at both 0° and 30° (P ≥ .288). Likewise, an SS strap tear with full-load transfer to the SS cord showed a similar recovery to native values at both 0° and 30° (P ≥ .155). During full-load transfer, the tendon strain followed the loading pattern. An SS cord tear or SS strap tear did not cause a change in humeral translation (P ≥ .303). DISCUSSION: The mechanical findings support the efficacy of nonoperative treatment of small (<10 mm) SS tears,11 because an intact SS strap tendon can effectively offset the abduction loss of a torn SS cord tear and vice versa.

Longitudinal study of traumatic-stress related cellular and cognitive aging.

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aß) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5.6 years. Cross-lagged panel mediation models evaluated measures of lifetime posttraumatic stress disorder and internalizing and externalizing comorbidity (assessed at Time 1; T1) in association with T1 epigenetic age (per the GrimAge algorithm) and T1 plasma markers of neuropathology along with bidirectional temporal paths between T1 and T2 epigenetic age and the plasma markers. Results revealed that a measure of externalizing comorbidity was associated with accelerated epigenetic age (ß = 0.30, p <.01), which in turn, was associated with subsequent increases in Aß-40 (ß = 0.20, p <.001), Aß-42 (ß = 0.18, p <.001), and interleukin-6 (ß = 0.18, p <.01). T1 advanced epigenetic age and the T1 neuropathology biomarkers NFL and glial fibrillary acidic protein predicted worse performance on T2 neurocognitive tasks assessing working memory, executive/attentional control, and/or verbal memory (ps = 0.03 to 0.009). Results suggest that advanced GrimAge is predictive of subsequent increases in neuropathology and inflammatory biomarkers as well as worse cognitive function, highlighting the clinical significance of this biomarker with respect to cognitive aging and brain health over time. The finding that advanced GrimAge mediated the association between psychiatric comorbidity and future neuropathology is important for understanding potential pathways to neurodegeneration and early identification of those at greatest risk.

Knee extensor torque-velocity relationships following anterior cruciate ligament reconstruction.

BACKGROUND: The inherent nature of the torque-velocity relationship is the inverse nature between the velocity of muscle contraction and torque production and is an indication of muscle function. The purpose of this study was to characterize the torque-velocity relationship in the quadriceps following anterior cruciate ligament reconstruction compared to healthy limbs. METHODS: 681 participants were included, 493 of which were patients at least four months following anterior cruciate ligament reconstruction (23.2 ± 10.08 yr, 6.6 ± 5.37 months post-surgery) and 188 were healthy participants (21.6 ± 3.77 yr). A subset of 175 post-surgical participants completed a repeated visit (8.1 ± 1.71 months post-surgery). Participants completed isokinetic knee extension at 90°/s and 180°/s. A one-way ANOVA was used to compare torque velocity relationships by limb type (surgical, contralateral, healthy). Paired samples t-tests were conducted to analyze the torque-velocity relationship across limbs and across time. FINDINGS: There was a large effect for limb type on torque-velocity (F(2, 1173) = 146.08, p < 0.001, η2 = 0.20). Surgical limbs demonstrated significantly lower torque-velocity relationships compared to the contralateral limbs (ACLR: 0.26 Nm/kg, contralateral:0.55 Nm/kg, p < 0.001, d = 1.18). Healthy limbs had similar torque-velocity relationships bilaterally (dominant limb: 0.48 Nm/kg, non-dominant limb: 0.49 Nm/kg, p = 0.45). The torque velocity relationship for the involved limb significantly increased in magnitude over time (+0.11 Nm/kg, p < 0.001, d = -0.61) while the contralateral limb torque-velocity relationship remained stable over time (0.0 Nm/kg difference, p = 0.60). INTERPRETATION: Following surgery, the knee extensors appear to have altered torque-velocity relationships compared to contralateral and healthy limbs. This may indicate a specific target for assessment and rehabilitation following surgery.

Skeletal Muscle Function Is Altered in Male Mice on Low-Dose Androgen Receptor Antagonist or Estrogen Receptor Agonist.

In males, skeletal muscle function may be altered by shifts in either circulating testosterone or estrogen. We examined the effect of acute (2-week) exposures to 17α-ethinyl estradiol (EE2), an estrogen receptor (ER) agonist, or flutamide, an androgen receptor (AR) antagonist, on the contractile function of individual skeletal muscle fibers from slow-contracting soleus and fast-contracting extensor digitorum longus muscles from adult male mice. Single fiber specific tension (force divided by cross-sectional area) was decreased with flutamide treatment in all myosin heavy chain (MHC) fiber types examined (I, IIA, and IIB); similar effects were observed with EE2 treatment but only in the fastest-contracting MHC IIB fibers. The decreases in maximally Ca2+-activated specific tension were primarily a result of fewer strongly bound myosin-actin cross-bridges, with flutamide treatment also showing lower myofilament lattice stiffness. Myosin-actin cross-bridge kinetics were slower in MHC IIA fibers in flutamide-treated mice, but faster in EE2-treated mice, indicating that contractile velocity may be affected differently in this fiber type, which is commonly expressed in human skeletal muscle. Importantly, these effects were observed in the absence of outcomes previously used to evaluate ER agonists or AR antagonists in rodents including weight of reproductive organs or mammary gland morphology. Our findings indicate that substantial shifts in skeletal muscle function occur in male mice following acute exposures to low doses of a pharmacological ER agonist and an AR antagonist. These results suggest that countermeasures to maintain physical function may be needed early in situations that induce similar ER agonist and AR antagonist conditions.

Primary Prevention and Interception Studies in RAS-Mutated Tumor Models Employing Small Molecules or Vaccines.

Therapeutic targeting of RAS-mutated cancers is difficult, whereas prevention or interception (treatment before or in the presence of preinvasive lesions) preclinically has proven easier. In the A/J mouse lung model, where different carcinogens induce tumors with different KRAS mutations, glucocorticoids and retinoid X receptor (RXR) agonists are effective agents in prevention and interception studies, irrespective of specific KRAS mutations. In rat azoxymethane-induced colon tumors (45% KRAS mutations), cyclooxygenase 1/2 inhibitors and difluoromethylornithine are effective in preventing or intercepting KRAS-mutated or wild-type tumors. In two KRAS-mutant pancreatic models multiple COX 1/2 inhibitors are effective. Furthermore, combining a COX and an EGFR inhibitor prevented the development of virtually all pancreatic tumors in transgenic mice. In the N-nitroso-N-methylurea-induced estrogen receptor-positive rat breast model (50% HRAS mutations) various selective estrogen receptor modulators, aromatase inhibitors, EGFR inhibitors, and RXR agonists are profoundly effective in prevention and interception of tumors with wild-type or mutant HRAS, while the farnesyltransferase inhibitor tipifarnib preferentially inhibits HRAS-mutant breast tumors. Thus, many agents not known to specifically inhibit the RAS pathway, are effective in an organ specific manner in preventing or intercepting RAS-mutated tumors. Finally, we discuss an alternative prevention and interception approach, employing vaccines to target KRAS.

Survey of adherence to sepsis care bundles in six European countries shows low adherence and possible patient risk.

Sepsis is a life-threatening condition which globally claims more lives than cancer. A set of evidence-based clinical practices (sepsis bundles) have been developed to guide early diagnosis and rapid intervention, which are vital to patient survival; however, their use is not widely adopted. A cross-sectional survey was administered in June-July 2022 to understand healthcare practitioner (HCP) knowledge of and adherence to sepsis bundles and identify key barriers to adherence in the UK, France, Spain, Sweden, Denmark and Norway; a total of n=368 HCPs ultimately participated. The results showed that among HCPs, overall awareness of sepsis and the importance of early diagnosis and treatment is high. However, there are indications that adherence to sepsis bundles is well below the standard of care: when asked which steps providers carry out to treat sepsis, only 44% report carrying out all steps in the bundle; and 66% of providers agreed that delays in sepsis diagnosis occur sometimes where they work. This survey also highlighted the possible barriers which are impeding the implementation of optimal sepsis care: particularly high patient caseload and staff shortages. This research highlights important gaps and obstacles in reaching optimal care of sepsis in the surveyed countries. There is a need for healthcare leaders and policy-makers alike to advocate for increased funding for more staff and training to address existing knowledge gaps and improve patient outcomes.

Age and CRP Associated With Improved Tissue Pathogen Identification in Children With Blood Culture Negative Osteomyelitis: Results From the CORTICES Multicenter Database.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a relatively common condition in children, and identifying the offending pathogen with blood or tissue cultures aids in diagnosis and medical management while reducing treatment failure. Recent 2021 AHO clinical practice guidelines from the Pediatric Infectious Disease Society recommend obtaining routine tissue cultures, particularly in cases with negative blood cultures. The purpose of this study was to identify variables associated with positive tissue cultures when blood cultures are negative. METHODS: Children with AHO from 18 pediatric medical centers throughout the United States through the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study were evaluated for predictors of positive tissue cultures when blood cultures were negative. Cutoffs of predictors were determined with associated sensitivity and specificity. RESULTS: One thousand three children with AHO were included, and in 688/1003 (68.6%) patients, both blood cultures and tissue cultures were obtained. In patients with negative blood cultures (n=385), tissue was positive in 267/385 (69.4%). In multivariate analysis, age ( P <0.001) and C-reactive protein (CRP) ( P =0.004) were independent predictors. With age >3.1 years and CRP >4.1 mg/dL as factors, the sensitivity of obtaining a positive tissue culture when blood cultures were negative was 87.3% (80.9-92.2%) compared with 7.1% (4.4-10.9%) if neither of these factors was present. There was a lower ratio of methicillin-resistant Staphylococcus aureus in blood culture-negative patients who had a positive tissue culture 48/188 (25.5%), compared with patients who had both positive blood and tissue cultures 108/220 (49.1%). CONCLUSION: AHO patients with CRP ≤ 4.1 mg/dL and age under 3.1 years are unlikely to have clinical value from tissue biopsy that exceeds the morbidity associated with this intervention. In patients with CRP > 4.1 mg/dL and age over 3.1 years, obtaining a tissue specimen may add value; however, it is important to note that effective empiric antibiotic coverage may limit the utility of positive tissue cultures in AHO. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

Establishing a Consensus Definition of a Knee Fracture-Dislocation (Schenck Knee Dislocation V) Using a Global Modified Delphi Method.

BACKGROUND: Knee fracture-dislocations are complex injuries; however, there is no universally accepted definition of what constitutes a fracture-dislocation within the Schenck Knee Dislocation (KD) V subcategory. The purpose of this study was to establish a more precise definition for fracture patterns included within the Schenck KD V subcategory. METHODS: A series of clinical scenarios encompassing various fracture patterns in association with a bicruciate knee ligament injury was created by a working group of 8 surgeons. Utilizing a modified Delphi technique, 46 surgeons from 18 countries and 6 continents with clinical and academic expertise in multiligamentous knee injuries undertook 3 rounds of online surveys to establish consensus. Consensus was defined as ≥70% agreement with responses of either "strongly agree" or "agree" for a positive consensus or "strongly disagree" or "disagree" for a negative consensus. RESULTS: There was a 100% response rate for Rounds 1 and 2 and a 96% response rate for Round 3. A total of 11 fracture patterns reached consensus for inclusion: (1) nondisplaced articular fracture of the femur; (2) displaced articular fracture of the femur; (3) tibial plateau fracture involving the weight-bearing surface (with or without tibial spine involvement); (4) tibial plateau peripheral rim compression fracture; (5) posterolateral tibial plateau compression fracture, Bernholt type IIB; (6) posterolateral tibial plateau compression fracture, Bernholt type IIIA; (7) posterolateral tibial plateau compression fracture, Bernholt type IIIB; (8) Gerdy's tubercle avulsion fracture with weight-bearing surface involvement; (9) displaced tibial tubercle fracture; (10) displaced patellar body fracture; and (11) displaced patellar inferior pole fracture. Fourteen fracture patterns reached consensus for exclusion from the definition. Two fracture patterns failed to reach consensus for either inclusion or exclusion from the definition. CONCLUSIONS: Using a modified Delphi technique, this study established consensus for specific fracture patterns to include within or exclude from the Schenck KD V subcategory. LEVEL OF EVIDENCE: Prognostic Level V . See Instructions for Authors for a complete description of levels of evidence.

A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.

Differentially methylated regions (DMRs) are genomic regions with methylation patterns across multiple CpG sites that are associated with a phenotype. In this study, we proposed a Principal Component (PC) based DMR analysis method for use with data generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC) array. We obtained methylation residuals by regressing the M-values of CpGs within a region on covariates, extracted PCs of the residuals, and then combined association information across PCs to obtain regional significance. Simulation-based genome-wide false positive (GFP) rates and true positive rates were estimated under a variety of conditions before determining the final version of our method, which we have named DMRPC. Then, DMRPC and another DMR method, coMethDMR, were used to perform epigenome-wide analyses of several phenotypes known to have multiple associated methylation loci (age, sex, and smoking) in a discovery and a replication cohort. Among regions that were analysed by both methods, DMRPC identified 50% more genome-wide significant age-associated DMRs than coMethDMR. The replication rate for the loci that were identified by only DMRPC was higher than the rate for those that were identified by only coMethDMR (90% for DMRPC vs. 76% for coMethDMR). Furthermore, DMRPC identified replicable associations in regions of moderate between-CpG correlation which are typically not analysed by coMethDMR. For the analyses of sex and smoking, the advantage of DMRPC was less clear. In conclusion, DMRPC is a new powerful DMR discovery tool that retains power in genomic regions with moderate correlation across CpGs.

Extensor Mechanism Disruption Impacts Treatment of Dislocated and Multiligament Injured Knees: Treatment and Schenck Classification Recommendations Based on a Global Delphi Method.

BACKGROUND: Multiligament knee injury (MLKI) with associated extensor mechanism (EM) involvement is a rare injury, with limited evidence to guide optimal treatment. The purpose of this study was to identify areas of consensus among a group of international experts regarding the treatment of patients with MLKI and concomitant EM injury. METHODS: Utilizing a classic Delphi technique, an international group of 46 surgeons from 6 continents with expertise in MLKI undertook 3 rounds of online surveys. Participants were presented with clinical scenarios involving EM disruption in association with MLKI, classified using the Schenck Knee-Dislocation (KD) Classification. Positive consensus was defined as ≥70% agreement with responses of either "strongly agree" or "agree," and negative consensus was defined as ≥70% agreement with "strongly disagree" or "disagree." RESULTS: There was a 100% response rate for rounds 1 and 2 and a 96% response rate for round 3. There was strong positive consensus (87%) that an EM injury in combination with MLKI significantly alters the treatment algorithm. For an EM injury in conjunction with a KD2, KD3M, or KD3L injury, there was positive consensus to repair the EM injury only and negative consensus regarding performing concurrent ligamentous reconstruction at the time of initial surgery. CONCLUSIONS: In the setting of bicruciate MLKI, there was overall agreement on the significant impact of EM injury on the treatment algorithm. We therefore recommend that the Schenck KD Classification be updated with the addition of the modifier suffix "-EM" to highlight this impact. Treatment of the EM injury was judged to have the highest priority, and there was consensus to treat the EM injury only. However, given the lack of clinical outcome data, treatment decisions need to be made on a case-by-case basis with consideration of the numerous clinical factors that are encountered. CLINICAL RELEVANCE: Little clinical evidence exists to guide the surgeon on the management of EM injury in the setting of a multiligament injured or dislocated knee. This survey highlights the impact that EM injury has on the treatment algorithm and provides some guidance for management until a further large case series or prospective studies are undertaken.

The Posterior Trans-Septal Portal in Knee Arthroscopy Review of the Technique Evolution, Indications, and Technical Pearls.

Complete arthroscopic visualization of the posterior com-partment of the knee is limited when using the traditional anterior portals. The trans-septal portal technique, created in 1997, has allowed surgeons to view the complete posterior compartment of the knee in a less-invasive way compared to open surgery. Since the description of the posterior trans-septal portal, several authors have modified the technique. However, the paucity of literature describing the trans-septal portal technique hints that widespread arthroscopic adop-tion has not yet been achieved. While still in its infancy, the literature has cumulatively reported over 700 successful knee surgeries using the posterior trans-septal portal technique with no reports of neurovascular injury. However, creation of the trans-septal portal carries risks due to its close prox-imity to the popliteal and middle geniculate artery, giving surgeons little room for technical error when developing this portal. Knowledge of the posterior anatomy, the evolution of the trans-septal portal, and current recommendations and safety options for using the technique will benefit orthopedic surgeons looking to incorporate this technique into their surgical arsenal. Furthermore, utilization of the trans-septal portal technique offers a significant benefit to the surgical treatment of conditions that involve the need for posterior knee access or visualization.