Global brain dynamics embed the motor command sequence of Caenorhabditis elegans.

While isolated motor actions can be correlated with activities of neuronal networks, an unresolved problem is how the brain assembles these activities into organized behaviors like action sequences. Using brain-wide calcium imaging in Caenorhabditis elegans, we show that a large proportion of neurons across the brain share information by engaging in coordinated, dynamical network activity. This brain state evolves on a cycle, each segment of which recruits the activities of different neuronal sub-populations and can be explicitly mapped, on a single trial basis, to the animals' major motor commands. This organization defines the assembly of motor commands into a string of run-and-turn action sequence cycles, including decisions between alternative behaviors. These dynamics serve as a robust scaffold for action selection in response to sensory input. This study shows that the coordination of neuronal activity patterns into global brain dynamics underlies the high-level organization of behavior.

Interferometer for Dispersive Measurements.

We suggest the use of broadband frequency modulation to construct a novel type of optical interferometer. This interferometer is insensitive to optical phase and allows measurement of the group velocity and group velocity dispersion without the need for short pulse apparatus.

Tape-Reinforced Graft Suturing and Retensioning of Adjustable-Loop Cortical Buttons Improve Quadriceps Tendon Autograft Biomechanics in Anterior Cruciate Ligament Reconstruction: A Cadaveric Study.

PURPOSE: To investigate the biomechanical effects of tape-reinforced graft suturing and graft retensioning for all-soft tissue quadriceps tendon (ASTQT) anterior cruciate ligament reconstruction (ACLR) in a full-construct human cadaveric model. METHODS: Harvested cadaveric ASTQT grafts were assigned to either (1) double-suspensory adjustable-loop cortical button device (ALD) fixation in which both graft ends were fixed with a suspensory fixation device with (n = 5) or without (n = 5) tape-reinforced suturing or (2) single-suspensory distal tendon fixation in which only the patellar end was fixed with an ALD (n = 5) or fixed-loop cortical button device (FLD) (n = 5). All specimens were prepared using a No. 2 whipstitch technique, and tape-reinforced specimens had an integrated braided tape implant. Graft preparation time was recorded for double-suspensory constructs. Samples were tested on an electromechanical testing machine using a previously published protocol simulating rehabilitative kinematics and loading. RESULTS: Tape-reinforced graft suturing resulted in greater graft load retention after cycling (11.9% difference, P = .021), less total elongation (mean [95% confidence interval (CI)], 5.57 mm [3.50-7.65 mm] vs 32.14 mm [25.38-38.90 mm]; P < .001), greater ultimate failure stiffness (mean [95% CI], 171.9 N/mm [158.8-185.0 N/mm] vs 119.4 N/mm [108.7-130.0 N/mm]; P < .001), and less graft preparation time (36.4% difference, P < .001) when compared with unreinforced specimens. Retensioned ALD constructs had less cyclic elongation compared with FLD constructs (mean total elongation [95% CI], 7.04 mm [5.47-8.61 mm] vs 12.96 mm [8.67-17.26 mm]; P = .004). CONCLUSIONS: Tape-reinforced graft suturing improves time-zero ASTQT ACLR construct biomechanics in a cadaveric model with 83% less total elongation, 44% greater stiffness, and reduced preparation time compared with a whipstitched graft without tape reinforcement. ALD fixation improves construct mechanics when compared with FLD fixation as evidenced by 46% less total elongation. CLINICAL RELEVANCE: Tape-reinforced implants and graft retensioning using ALDs improve time-zero ACLR graft construct biomechanics in a time-zero biomechanical model. Clinical studies will be necessary to determine whether these implants improve clinical outcomes including knee laxity and the incidence of graft rupture.

Most Publications Regarding Platelet-Rich Plasma Use in the Knee Are From Asia, Investigate Injection for Osteoarthritis, and Show Outcome Improvement: A Scoping Review.

PURPOSE: To evaluate and synthesize the available literature related to platelet-rich plasma (PRP) treatment of knee pathologies and to provide recommendations to inform future research in the field. METHODS: PubMed, CINAHL, and Scopus databases were queried on October 6, 2023. All identified citations were collated and uploaded into Covidence for screening and data extraction. Studies were included if they were human studies published in English with adult cohorts that received PRP as a procedural injection or surgical augmentation for knee pathologies with patient-reported outcome measures (PROMs) and level of evidence Levels I-IV. RESULTS: Our search yielded 2,615 studies, of which 155 studies from 2006 to 2023 met the inclusion criteria. Median follow-up was 9 months (±11.2 months). Most studies (75.5%) characterized the leukocyte content of PRP, although most studies (86%) did not use a comprehensive classification scheme. In addition, most studies were from Asia (50%) and Europe (32%) and were from a single center (96%). In terms of treatment, 74% of studies examined PRP as a procedural injection, whereas 26% examined PRP as an augmentation. Most studies (68%) examined treatment of knee osteoarthritis. Many studies (83%) documented significant improvements in PROMs, including 93% of Level III/IV evidence studies and 72% of Level I/II evidence studies, although most studies (70%) failed to include minimal clinically important difference values. The visual analog scale was the most-used PROM (58% of studies), whereas the Short Form Health Survey 36-item was the least-used PROM (5% of studies). CONCLUSIONS: Most published investigations of knee PRP are performed in Asia, investigate procedural injection for osteoarthritis, and show significant outcome improvements. In addition, this review highlights the need for better classification of PRP formulations. LEVEL OF EVIDENCE: Level IV, scoping Review of level I-IV studies.

Distinct risk profiles for short-term surgical complications and venous thromboembolism exist among extensor mechanism repair procedures.

PURPOSE: Extensor mechanism injuries, which comprise patella fractures, patella tendon tears and quadriceps tendon tears, are severely debilitating injuries and a common cause of traumatic knee pathology that requires surgical intervention. Risk factors for short-term surgical complications and venous thromboembolism (VTE) in this population have not been well characterised. The aim of this study was to identify perioperative risk factors associated with these short-term complications. METHODS: The National Surgical Quality Improvement Program database was used to identify patients who underwent an isolated, primary extensor mechanism repair from 2015 to 2020. Patients were stratified by injury type. Demographic data were collected and compared. A multivariate logistic regression was used to control for demographic and comorbid factors while assessing risk factors for developing short-term complications. RESULTS: A total of 8355 patients were identified for inclusion in this study. Overall, 3% of patients sustained short-term surgical complications and 1% were diagnosed with VTE within 30 days of surgery. Patella fracture fixation had a nearly twofold higher risk for surgical complications compared to quadriceps tendon repair (p = 0.004). Patella tendon repair had a twofold higher risk for VTE (p = 0.045), specifically deep vein thrombosis (p = 0.020), compared to patella fracture fixation. Increasing age, smoking and American Society of Anesthesiologists Classifications 3 and 4 were also found to be risk factors for surgical complications (p = 0.012, p = 0.004, p = 0.011 and p = 0.032, respectively). CONCLUSION: This study used a nationally representative, widely validated, peer-reviewed database to provide valuable insights into risk factors for short-term postoperative complications associated with extensor mechanism repair procedures, revealing notable differences in risk profiles among distinct surgical procedures. The results of this study will inform surgeons and patients in enhancing risk assessment, guiding procedure-specific decision-making, optimising preoperative care, improving postoperative monitoring and contributing to future research of extensor mechanism injuries. LEVEL OF EVIDENCE: Level III.

Creation of forest edges has a global impact on forest vertebrates.

Forest edges influence more than half of the world's forests and contribute to worldwide declines in biodiversity and ecosystem functions. However, predicting these declines is challenging in heterogeneous fragmented landscapes. Here we assembled a global dataset on species responses to fragmentation and developed a statistical approach for quantifying edge impacts in heterogeneous landscapes to quantify edge-determined changes in abundance of 1,673 vertebrate species. We show that the abundances of 85% of species are affected, either positively or negatively, by forest edges. Species that live in the centre of the forest (forest core), that were more likely to be listed as threatened by the International Union for Conservation of Nature (IUCN), reached peak abundances only at sites farther than 200-400 m from sharp high-contrast forest edges. Smaller-bodied amphibians, larger reptiles and medium-sized non-volant mammals experienced a larger reduction in suitable habitat than other forest-core species. Our results highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.

Quadriceps tendon autograft has similar clinical outcomes when compared to hamstring tendon and bone-patellar tendon-bone autografts for revision ACL reconstruction: a systematic review and meta-analysis.

PURPOSE: Research regarding revision anterior cruciate ligament reconstruction (RACLR) with quadriceps tendon (QT) autografts is lacking. The purpose of this study was to perform a systematic review and meta-analysis of RACLR with QT and compare its patient outcomes to RACLR with hamstring tendon (HT) and bone-patellar tendon-bone (BTB) autografts. METHODS: Adhering to PRISMA guidelines, a search for studies using QT in RACLR was performed within PubMed, Scopus, and CINAHL from database date of inception through December 26, 2022. Primary outcomes sought included: failure rate, Lysholm scores, International Knee Documentation Committee (IKDC) scores, IKDC grades, arthrometric knee side-to-side differences (STSD), pivot shift grade, donor site morbidity, return to sport, visual analog scale (VAS) pain scores. RESULTS: Nine studies were included consisting of 606 RACLR: 349 QT, 169 HT, and 88 BTB. Overall failure rates were 7.6% QT, 13.3% HT, and 8.7% BTB. Mean weighted Lysholm scores were 85.8 ± 3.8 QT, 82.5 ± 3.8 HT and 86.6 ± 4.5 BTB. IKDC average scores were 82.3 ± 1.6 QT, 80.1 ± 1.7 HT, and 81.7 ± 5.5BTB. Combined rates of IKDC A/B grades were 88.4% and 80.0% for QT and HT, respectively. VAS average scores were 0.9 ± 1.1 QT, 1.4 ± 0.2 HT, and 0.7 ± 0.8 for BTB. Side-to-side difference was reported for QT and HT with average values of 1.7 ± 0.6 mm and 2.1 ± 0.5 mm, respectively. Grade 0 or 1 pivot shifts were reported in 96.2% of QT patients and 91.3% of HT. Donor site morbidity, only reported for QT and HT, was 14.6 ± 9.7% and 23.6 ± 14.1%, respectively. QT resulted in a mean Tegner score of 5.9 ± 1.5 versus HT 5.7 ± 1.5. Rate of return to pivoting sports was 38.0% QT, 48.6% HT, and 76.9% BTB. Across all outcomes, there was no significant difference when comparing QT to HT, QT to BTB, and QT compared to HT and BTB combined. CONCLUSIONS: RACLR with QT yields satisfactory patient reported outcomes, satisfactory improvement in knee laxity, expected return to sport rates, and has an overall 7.6% failure rate. Outcomes are comparative to those of HT and BTB making it an acceptable graft choice for RACLR. Surgeons should consider using QT autograft for RACLR, especially when other autografts are unavailable. LEVEL OF EVIDENCE: IV.

Three major dimensions of human brain cortical ageing in relation to cognitive decline across the eighth decade of life.

Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.

All-Inside Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed knee operations. An "all-inside" technique creates bone sockets for ACL graft passage, as opposed to more traditional full bone tunnels, and typically incorporates suspensory fixation instead of screw fixation to secure the graft. This technique may be indicated for any ACL reconstruction surgery, where adequate bone stock exists to drill sockets and to use cortical fixation. The technique may be used with all soft tissue, as well as bone plug ACL grafts and autograft hamstring or quadriceps tendon; most allograft tendon options may be performed with an all-inside technique. Advantages include anatomic tunnel/socket placement, decreased postoperative pain and swelling, minimal hardware, appropriate graft tensioning and retensioning, and circumferential graft to bone healing. Tips for successful all-inside surgery include matching graft diameter to socket diameter, drilling appropriate length sockets based on individual graft length, so as not to "bottom out" the graft and confirming cortical button fixation intraoperatively. Potential complications include graft-socket mismatch, full-tunnel reaming, and loss of cortical fixation. Multiple studies have shown the all-inside technique to have similar or superior biomechanical properties and clinical outcomes compared to the more traditional full-tunnel ACL reconstruction techniques.

Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial.

PURPOSE: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. METHODS: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. RESULTS: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. CONCLUSION: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. TRIAL REGISTRATION: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063.

Subgingival microbiota of dogs with healthy gingiva or early periodontal disease from different geographical locations.

BACKGROUND: Periodontal disease is the most common oral disease of dogs worldwide and results from a complex interplay between plaque bacteria, the host and environmental factors. Recent studies have enhanced our understanding of the associations between the plaque microbiota and canine periodontal disease. These studies, however, were limited in their geographical reach. Thus associations between the canine oral microbiota and geographical location were investigated by determining the composition of subgingival plaque samples from 587 dogs residing in the United Kingdom (UK), United States of America (USA), China and Thailand using 454-pyrosequencing. RESULTS: After quality filtering 6,944,757 sequence reads were obtained and clustering of these at ≥98% sequence resulted in 280 operational taxonomic units (OTUs) following exclusion of rare OTUs (present at < 0.05% in all four countries). The subgingival plaque from dog populations located in the UK, USA, China and Thailand had a similar composition although the abundance of certain taxa varied significantly among geographical locations. Exploration of the effect of clinical status and age revealed a marked similarity among the bacteria associated with increased age and those associated with gingivitis: Young dogs and those with no gingivitis were dominated by taxa from the phyla Bacteroidetes and Proteobacteria whereas older dogs and those with moderate gingivitis were dominated by members of the Firmicutes. The plaque microbiota of small breed dogs was found to significantly differ to medium and large breeds and was dominated by species belonging to the Firmicutes. CONCLUSIONS: The bacterial associations with health, gingivitis and periodontitis were conserved across dogs from the UK, USA, China and Thailand. These bacterial signatures of periodontal health and disease have potential as biomarkers for disease detection.

Perceptions of UK clinicians towards postoperative critical care.

Postoperative critical care is a finite resource that is recommended for high-risk patients. Despite national recommendations specifying that such patients should receive postoperative critical care, there is evidence that these recommendations are not universally followed. We performed a national survey aiming to better understand how patients are risk-stratified in practice; elucidate clinicians' opinions about how patients should be selected for critical care; and determine factors which affect the actual provision of postoperative critical care. As part of the second Sprint National Anaesthesia Project, epidemiology of critical care after surgery study, we distributed a paper survey to anaesthetists, surgeons and intensivists providing peri-operative care during a single week in March 2017. We collected data on respondent characteristics, and their opinions of postoperative critical care provision, potential benefits and real-world challenges. We undertook both quantitative and qualitative analyses to interpret the responses. We received 10,383 survey responses from 237 hospitals across the UK. Consultants used a lower threshold for critical care admission than other career grades, indicating potentially more risk-averse behaviour. The majority of respondents reported that critical care provision was inadequate, and cited the value of critical care as being predominantly due to higher nurse: patient ratios. Use of objective risk assessment tools was poor, and patients were commonly selected for critical care based on procedure-specific pathways rather than individualised risk assessment. Challenges were highlighted in the delivery of peri-operative critical care services, such as an overall lack of capacity, competition for beds with non-surgical cases and poor flow through the hospital leading to bed 'blockages'. Critical care is perceived to provide benefit to high-risk surgical patients, but there is variation in practice about the definition and determination of risk, how patients are referred and how to deal with the lack of critical care resources. Future work should focus on evaluating 'enhanced care' units for postoperative patients, how to better implement individualised risk assessment in practice, and how to improve patient flow through hospitals.

Long-term safety and efficacy of a fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis: phase 3 open-label study.

BACKGROUND: The topical corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (TAZ) are effective in psoriasis treatment. To mitigate adverse cutaneous reactions observed with monotherapy, a fixed- combination HP 0.01%/TAZ 0.045% lotion has been developed for the treatment of plaque psoriasis in adults. OBJECTIVES: To investigate the long-term safety, efficacy and maintenance of response with HP/TAZ lotion. METHODS: This was a 1-year, multicentre, open-label study in 555 adults with psoriasis [Investigator's Global Assessment (IGA) score of 3 ('moderate') or 4 ('severe') and body surface area (BSA) of 3-12% at baseline]. HP/TAZ was administered once daily for 8 weeks and then intermittently as needed in 4-week intervals for up to 1 year based on achievement of treatment success [IGA score of 0 ('clear') or 1 ('almost clear')]. Maximum continuous exposure was 24 weeks. RESULTS: Of 550 participants with postbaseline safety data, 318 (57.8%) achieved treatment success during the study. Of those, 54.4% achieved treatment success within the first 8 weeks; retreatment was not required for >4 weeks in over half (55.3%), and 6.6% did not require any retreatment. Among participants enrolled for the full 52 weeks, 77.5% maintained BSA ≤5% on treatment. There were marked improvements in severity of itching, dryness and burning/stinging over the study course. The most common treatment-related adverse events were application site reactions of dermatitis, pruritus, pain and irritation. CONCLUSIONS: Fixed-combination HP/TAZ lotion provided maintained efficacy with a favourable tolerability and safety profile, supporting its use for the long-term treatment and management of moderate-to-severe plaque psoriasis.

Combined Oral Contraceptive Use Increases the Risk of Venous Thromboembolism After Knee Arthroscopy and Anterior Cruciate Ligament Reconstruction: An Analysis of 64,165 Patients in the Truven Database.

PURPOSE: To use the Truven MarketScan database to (1) report the incidence of venous thromboembolism (VTE), including deep vein thromboses (DVTs) and pulmonary embolism (PE), in patients undergoing simple knee arthroscopy and anterior cruciate ligament (ACL) reconstruction, and (2) evaluate combined oral contraceptive (COCP) use as a potential risk factor for VTE in patients undergoing knee arthroscopy. METHODS: All female patients between the ages of 16 and 40 years undergoing knee arthroscopy and ACL reconstruction between 2010 and 2015 were identified in the MarketScan database. Patients were stratified by whether they had a documented pharmaceutical claim for COCP therapy, and the primary outcome was the risk of DVT and or PE within 90 postoperative days. RESULTS: In total, 64,165 patients were identified for inclusion. While the overall incidence of VTE was low, patients taking COCPs had an increased risk of a DVT or PE compared with those not on COCPs (odds ratio [OR] 2.1, P < .001). When patients were analyzed by procedural subgroup (ACL reconstruction and simple knee arthroscopy), similar results held true. Furthermore, smoking and obesity had a synergistic effect when combined with COCPs use on the risk of VTE. Specifically, 3.1% of patients with obesity on COCPs (OR 3.1, P < .001) and 4.0% of smokers on COCPs (OR 4.3, P < .001) developed a postoperative VTE. CONCLUSIONS: This study demonstrates that COCP use is associated with an increased risk for a symptomatic DVT or PE (1.70% and 0.27%, respectively) after knee arthroscopy and an increased risk for DVT, but not PE (1.80% and 0.23%, respectively), after ACL reconstruction. In addition, patients with multiple risk factors present such as tobacco use, obesity, and COCP use had odds ratios greater than the sum of the individual risk factors alone. LEVEL OF EVIDENCE: level III prognostic cohort study.

Increased Risk of Short-Term Complications and Venous Thromboembolism in Latarjet-Bristow Procedures Compared With Bankart Repairs.

PURPOSE: To (1) determine the rate of surgical complications and venous thromboembolism (VTE) in patients undergoing arthroscopic Bankart repair, open Bankart repair, or Latarjet-Bristow; and (2) assess potential risk factors for surgical complications and VTE in patients undergoing shoulder stabilization procedures. METHODS: The NSQIP database was used to identify patients undergoing isolated surgery for shoulder instability from 2005 to 2017. Demographic data were collected and compared. Logistic regression was used to assess the risk factors for developing a postoperative complication, and regression analyses were used to evaluate the odds of postoperative complications between types of surgery. RESULTS: We identified 7,233 patients for inclusion. Patients undergoing Latarjet-Bristow were more likely to be male and Black and to report current tobacco use. Overall, there was a low rate of surgical complications (0.4%) and VTE (0.2%). However, patients undergoing Latarjet-Bristow had nearly a 10-fold increase in the risk of surgical complications compared with an arthroscopic or open Bankart repair (1.9% versus 0.2%, P < .001), including deep surgical site infections, return to operating room within 30 days, and symptomatic VTE (deep venous thrombosis rate: arthroscopic Bankart repair, 0.1%; Latarjet-Bristow, 0.8%; P < .001). There were no differences in the odds of developing a surgical complication or VTE between patients undergoing arthroscopic or open Bankart repair. CONCLUSION: This study used a nationally representative, widely validated, peer-reviewed database to demonstrate that patients undergoing a Latarjet-Bristow procedure are at significantly higher risk for short-term postoperative complications, including deep surgical site infections, return to the operating room, and symptomatic VTE, than those undergoing Bankart repair. These findings should not discourage surgeons from proceeding with a coracoid transfer procedure when indicated for glenoid deficiencies, but should inform preoperative counseling and help guide perioperative care to optimize patient outcomes. LEVEL OF EVIDENCE: III, retrospective comparative trial.

Revision Anterior Cruciate Ligament Reconstruction with the All-Soft Tissue Quadriceps Tendon Autograft Has Acceptable Early and Intermediate-Term Outcomes.

PURPOSE: The purposes were to (1) examine early to intermediate-term clinical outcomes and complications of revision anterior cruciate ligament reconstruction (ACLR) using all-soft tissue quadriceps tendon (QT) autografts, and (2) compare quadriceps strength between patients who had hamstring versus patella tendon autografts in their previous reconstruction. METHODS: One hundred patients (52 males/48 females; 22.6 ± 8.0 years) undergoing revision ACLR with all-soft tissue QT autografts were prospectively followed. All revision procedures were performed by a single surgeon, using a minimally invasive graft harvest technique and suspensory fixation. Subjective assessment of knee function was obtained before and after surgery with the International Knee Documentation Committee (IKDC) survey. Postoperative knee laxity and isokinetic quadriceps strength were collected at regular intervals. Strength was reported as limb symmetry index (LSI; surgical side divided by nonsurgical side). Complications including hematomas, postoperative loss of knee extension, and graft failures were recorded. To determine clinical significance (P ≤ .05), outcomes were compared using analysis of variance or paired samples t-tests. RESULTS: The mean IKDC scores significantly improved (54.3 ± 13.0 vs 82.8 ± 13.8), with an average follow-up of 42.2 ± 21.2 months. There were no significant changes in knee laxity side-to-side differences: 6 weeks (1.2 ± 1.5 mm), 3 months (1.2 ± 1.8 mm), 6 months (1.4 ± 1.6 mm). Quadriceps LSIs significantly improved from 71.6% ± 19.3% at 6 months to 81.5% ± 19.3% at 12 months for 60°/s isokinetic testing and 76.6% ± 16.4% at 6 months to 83.9% ± 16.9% at 12 months for 180°/s testing. Graft harvest site hematomas developed in 2 patients, postoperative loss of knee extension in 4 patients, and graft failure in 11 patients. No significant differences in quadriceps or hamstrings LSIs were noted between patients with previous hamstring versus patella tendon autografts (P > .050). CONCLUSION: Revision ACLR with all-soft tissue QT autografts has acceptable early and intermediate-term outcomes with reasonable complication rates (11/80 patients with follow-up). Secondary insult to the extensor mechanism via QT autograft harvest does not adversely affect strength after prior patellar tendon versus hamstring autograft. LEVEL OF EVIDENCE: Level IV, cases series subgroup analysis.

Shoulder Position During Magnetic Resonance Arthrogram Significantly Affects Capsular Measurements.

PURPOSE: To determine whether change in shoulder position between internal rotation (IR) and external rotation (ER) during magnetic resonance arthrography (MRA) affects previously defined capsular measurements and to determine the utility of rotation in the diagnosis of instability. METHODS: A retrospective study was conducted of patients who received a shoulder MRA with humeral IR and ER views. Patients with an arthroscopically confirmed diagnosis of instability and those with clinically stable shoulders, no history of instability, and no MRA findings of instability were identified and compared. Humeral rotation, glenoid retroversion, humeral head subluxation, capsular length, and capsular area using axial sequences of IR and ER views were recorded. Analysis compared IR, ER, and Δ capsular measurements between groups using independent t tests and univariate and multivariate regression. RESULTS: Thirty-one subjects who were diagnosed with instability were included, along with 28 control subjects. Capsular length, capsular area, and humeral subluxations were significantly greater with ER compared with IR views (P < .001, P < .001, P < .001). Patients with instability displayed greater ER capsular length (P = .0006) and ER capsular area (P = .005) relative to controls. Multivariate logistic regression identified age, weight, sex, ER capsular length, and retroversion to be significant predictors of instability. ER capsular length independently predicts instability with 86% sensitivity and 84% specificity. Interobserver reliability using the intraclass correlation coefficient was rated good or excellent on all measurements. CONCLUSION: Variance in humeral rotation during shoulder MRA significantly affects capsular measurements. Rotational views increase the utility of capsular measurements when assessing for instability, particularly capsular length and capsular area. The implementation of ER positioning enhances the ability to examine capsular changes of the shoulder joint and can assist in the diagnosis of instability. LEVEL OF EVIDENCE: III, retrospective comparative study.

Elevated BMI increases concurrent pathology and operative time in adolescent ACL reconstruction.

PURPOSE: The purpose of this study was to (1) report on the incidence of concurrent surgical pathology at the time of adolescent ACL reconstruction, (2) evaluate patient risk factors for concurrent pathology, and (3) measure the effect of BMI on operating room (OR) time. METHODS: A retrospective analysis of the NSQIP database for the years 2005-2017 was conducted. Nine-hundred and seventeen patients 18 years of age and younger who underwent ACL reconstruction (ACLR) were identified using CPT code 29888 and patients undergoing surgery for multi-ligamentous knee injuries were excluded. The mean patient age was 17.6 years (range 14-18, standard deviation 0.52) and consisted of 546 males (59.5%) and 371 females (40.5%). Logistic regression was used to assess the relationship between BMI and additional CPT codes for internal derangement at the time of surgery. Internal derangement was defined as any procedure for the treatment of a meniscal tear, chondral lesion, or loose body removal. Linear regression analysis was then performed to evaluate the effect of BMI on operative time. RESULTS: 43.7% of patients undergoing ACLR required an associated procedure for internal derangement. Additionally, the risk of requiring additional procedures for internal derangement increased by 3.1% per BMI point. BMI was also predictive of operative time, independent of the number of additional procedures. Specifically, the operative time increased by nearly one minute for every point increase in BMI (58.0 s). CONCLUSIONS: Adolescent patients with an elevated BMI were much more likely to require additional surgical procedures for internal derangement at the time of ACL reconstruction. Additionally, BMI was a significant predictor for longer operative times. LEVEL OF EVIDENCE: Level III.

Terminal knee extension deficit and female sex predict poorer quadriceps strength following ACL reconstruction using all-soft tissue quadriceps tendon autografts.

PURPOSE: The all-soft tissue quadriceps tendon (QT) autograft is becoming increasingly popular for ACL reconstruction (ACLR); however, studies reporting strength recovery and early outcomes after QT autograft are limited with patient samples composed of predominantly males. The primary purpose was to characterize early, sex-specific recovery of strength, range of motion (ROM), and knee laxity in a large cohort of patients undergoing primary ACLR with standardized harvest technique of the all-soft tissue QT autograft. The secondary purpose was to examine the influence of demographic factors and clinical measures on 6-month quadriceps strength. METHODS: Patients 14-25 years who underwent primary, unilateral ACLR with all-soft tissue QT autografts were prospectively followed. Knee laxity and ROM were collected at 6 weeks, 3 and 6 months; while, quadriceps normalized torques and limb symmetry indices (LSI) were collected at 3 and 6 months using isokinetic dynamometry at 60°/s. Two-way ANOVAs with repeated measures were conducted to determine recovery over time and between sexes. Stepwise linear multiple regressions were conducted to determine predictors of 6-month quadriceps strength. RESULTS: Three-hundred and twenty patients were included (18 ± 3 years; 156 males:164 females; BMI = 24 ± 4 kg/m2) with no early graft failures within the study period. For strength, there were significant main effects of time (p < 0.001) and sex (p < 0.001), indicating similar improvement from 3 to 6 months with males demonstrating greater quadriceps LSI (6 months: 72.1 vs 63.3%) and normalized strength (6 months: 2.0 vs 1.6 Nm/kg). A significantly higher proportion of females had knee extension ROM deficits ≥ 5° compared to males at 6 weeks (61 vs 39%; p = 0.002). Female sex and 3-month extension ROM deficits were identified as significant predictors of 6-month quadriceps LSI (R2 = 0.083; p < 0.001). Female sex, BMI, and 6-week extension ROM deficits were identified as significant predictors of 6-month normalized quadriceps strength (R2 = 0.190; p < 0.001). CONCLUSIONS: Females had decreased quadriceps strength and greater extension ROM deficits at 3 and 6 months following ACLR using all-soft tissue QT autografts. Female sex, higher BMI, and loss of extension ROM were independent predictors of poorer quadriceps strength at 6 months. There were no early graft failures, and laxity remained within normal ranges for both males and females. Surgeons and rehabilitation clinicians should be aware of the increased risk of postoperative loss of extension ROM in females and its implications on quadriceps strength recovery. LEVEL OF EVIDENCE: III.

Infigratinib in upper tract urothelial carcinoma versus urothelial carcinoma of the bladder and its association with comprehensive genomic profiling and/or cell-free DNA results.

BACKGROUND: Infigratinib (BGJ398) is a potent and selective fibroblast grown factor receptor 1 to 3 (FGFR1-3) inhibitor with significant activity in patients with advanced or metastatic urothelial carcinoma bearing FGFR3 alterations. Given the distinct biologic characteristics of upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB), the authors examined whether infigratinib had varying activity in these settings. METHODS: Eligible patients had metastatic urothelial carcinoma with activating FGFR3 mutations and/or fusions. Comprehensive genomic profiling was performed on formalin-fixed, paraffin-embedded tissues. Blood was collected for cell-free DNA analysis using a 600-gene panel. Patients received infigratinib at a dose of 125 mg orally daily (3 weeks on/1 week off) until disease progression or intolerable toxicity occurred. The overall response rate (ORR; partial response [PR] plus complete response [CR]) and disease control rate (DCR; CR plus PR plus stable disease [SD]) were characterized. RESULTS: A total of 67 patients were enrolled; the majority (70.1%) had received ≥2 prior antineoplastic therapies. In 8 patients with UTUC, 1 CR and 3 PRs were observed (ORR, 50%); the remaining patients achieved a best response of SD (DCR, 100%). In patients with UCB, 13 PRs were observed (ORR, 22%), and 22 patients had a best response of SD (DCR, 59.3%). Notable differences in genomic alterations between patients with UTUC and those with UCB included higher frequencies of FGFR3-TACC3 fusions (12.5% vs 6.8%) and FGFR3 R248C mutations (50% vs 11.9%), and a lower frequency of FGFR3 S249C mutations (37.5% vs 59.3%). CONCLUSIONS: Differences in the cumulative genomic profile were observed between patients with UTUC and those with UCB in the current FGFR3-restricted experience, underscoring the distinct biology of these diseases. These results support a planned phase 3 adjuvant study predominantly performed in this population.