Progressive Age-Associated Blood-Brain Barrier Leak/Dysfunction-Nexus of Neurodegenerative Disease Using MRI Markers to Identify Preclinical Disease and Potential New Targets for Future Treatments.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood-brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupting protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins mean a new approach to disease in the preclinical state is required aimed at other targets. Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required. This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak, and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Growth and Fruit morphometric characteristics of local avocado germplasm (Persea americana Mill.) grown in northern Tanzania.

Tanzania has a diverse agroecological area suitable for growing tropical fruits, including avocados. In Northern Tanzania, avocados have been growing under variable soil and altitudinal characteristics for over 100 years, allowing the naturalisation of this crop in this region. However, the region's avocado germplasm is uncharacterised, thus impeding the selection of elite genotypes for increased value and breeding programmes. This study examined the growth and fruit morphometric characteristics of avocado populations grown under variable soil pH and altitude in six districts in the Tanga, Kilimanjaro and Arusha regions. Variations in growth and fruit morphometric characteristics were compared using a one-way analysis of variance (ANOVA). Pearson product-moment correlations (r) were used to evaluate the relationship between studied growth and fruit morphometric traits. A linear mixed-effects model (LMM) was used to assess the influence of the soil pH, altitude, tree height, canopy diameter, and trunk diameter on fruit length, fruit diameter, pulp thickness, and seed diameter. Principal Component Analysis (PCA) was used to depict the extent of the racial admixtures in the avocado germplasm in the Northern regions of Tanzania. The results revealed a significant variation in growth and fruit morphometric characteristics (p < 0.05). The Korogwe population had the highest tree height, while the Karatu had the lowest. Tree height was positively correlated with the trunk diameter (r = 0.63, p < 0.001. There was a positive correlation between fruit length and pulp thickness (r = 0.51, p < 0.001), fruit diameter and pulp thickness (r = 0.47, p < 0.001), and fruit length and fruit diameter (r = 0.36, p < 0.001). The fruit diameter was positively correlated with the seed diameter (r = 0.61, p < 0.001). There was a significant but weak association between fruit length and trunk diameter (-0.01), fruit length and canopy diameter (0.15), and between seed diameter and tree height (2.95e-2). These findings highlight the influence of individual tree genetic makeup on the variation in growth and fruit morphometric characteristics. The morphometric trait correlations may prove valuable in field measurements, especially when resources are limited. The study further indicates the presence of all avocado races within the local germplasm, highlighting its high diversity. Remarkably, the observed admixture of variant races implies gene flow among studied avocado populations, possibly facilitated by sharing seedlings among farmers or seed disposal through avocado fruit trading. Further study is needed, particularly in quantifying the above-ground biomass of local avocados in northern Tanzania, potentially contributing to carbon credit initiatives for fruit crops..

Identifying delay in glymphatic clearance of labeled protons post-acute head trauma utilizing 3D ASL MRI (arterial spin labeling): a pilot study.

This study correlated mild traumatic brain injury (mTBI) cognitive changes with ASL-MRI glymphatic clearance rates (GCRs) and recovery with GCR improvement. mTBI disrupts the blood brain barrier (BBB), reducing capillary mean transit time and GCRs. mTBI is clinically diagnosed utilizing history/examination findings with no physiologic biomarkers. 3D TGSE (turbo-gradient spin-echo) pulsed arterial spin-labeling 3T MRI with 7 long inversion times (TIs) assessed the signal clearance of labeled protons 2800-4000 ms postlabeling in bifrontal, bitemporal, and biparietal regions within 7 days of mTBI and once clinically cleared to resume activities. The Sport Concussion Assessment Tool Version 5 (SKAT5) and Brief Oculomotor/Vestibular Assessment evaluated injured athletes' cognitive function prior to MRIs. The pilot study demonstrated significant GCRs improvement (95% CI - 0.06 to - 0.03 acute phase; to CI-recovery CI 0.0772 to - 0.0497; P < 0.001 in frontal lobes; and parietal lobes (95% CI - 0.0584 to - 0.0251 acute; CI - 0.0727 to - 0.0392 recovery; P = 0.024) in 9 mTBI athletes (8 female, 1 male). Six age/activity-matched controls (4 females, 2 males) were also compared. mTBI disrupts the BBB, reducing GCR measured using the 3D ASL MRI technique. ASL MRI is a potential noninvasive biomarker of mTBI and subsequent recovery.

Utilizing Reduced Labeled Proton Clearance to Identify Preclinical Alzheimer Disease with 3D ASL MRI.

Addressing the seminal pathophysiology in Alzheimer disease (AD) is the next logical focus for effective intervention, given the initial disappointing and more recent possibly encouraging results of monoclonal antibody trials. Endothelial cell dysfunction-induced blood-brain barrier leak with associated prolonged capillary mean transit time (cMTT) and glymphatic outflow dysfunction is the most proximal events in the degeneration cascade. Sensitive and reproducible markers are required to both identify early disease and assess future treatment trial outcomes. Two participants, with mild cognitive impairment (MCI) and one with AD, were evaluated clinically prior to MRI in this small case series report. From seven 3D turbo gradient and spin echo (TGSE) pulsed arterial spin echo (PASL) MRI sequences six homologous region of interest in bitemporal, bifrontal, and biparietal lobes for each sequence were examined and plotted against time. By choosing late perfusion times during cMTT phase of perfusion linear analysis of signal decay could be utilized. A reference axial FLAIR sequence was also obtained. Slope of the linear analysis correlated to the rate of labeled proton clearance with reduced clearance occurring in AD participants compared to normal participants in our previous study. Whether similar differences in clearance rate extend to either MCI or early AD was investigated. Participants were categorized by clinical phenotype before MRI and compared to previously published phenotype cohorts: n = 18 normal/healthy, n = 6 AD, n = 3 MCI. Significant differences in labeled proton clearance rates between AD and MCI/control phenotypes within bilateral temporal lobes (left p = 0.004, right p = 0.002) and within bilateral frontal lobes AD versus controls (left p = 0.001, right p = 0.008) and AD versus MCI (left p = 0.001, right p = 0.001) were found. This noninvasive MRI technique has potential for identifying MCI transition to AD.

Single-crystal quality data from polycrystalline samples: finding the needle in the haystack.

Multi-grain crystallography, traditionally performed at synchrotron sources in association with high-pressure studies, has new relevance with respect to laboratory single-crystal X-ray diffraction, in which crystals can be grown rapidly in situ, and a preliminary dataset analysed and solved in a matter of minutes. Subsequently, a full-sphere of IUCr-quality data can then be collected in a few hours. To demonstrate the applicability of laboratory multi-grain crystallography with Cu Kα X-rays, co-crystals of hexafluorobenzene and pyrrole were grown rapidly by cooling a 1:1 liquid mixture in an X-ray capillary on the diffractometer. The software is able to identify a single unit cell from as few as 10% of the diffraction spots from a small number of diffraction frames. Once a unit cell is identified, a full crystal structure solution is rapidly obtained by collecting a small amount of data to a resolution of ca 1 Å. The co-crystal obtained from the 1:1 mixture showed that hexafluorobenzene and pyrrole crystallize in a 3:4 ratio, in contrast to the columnar 1:1 adduct structures typified by hexafluorobenzene and benzene. The generality of our multi-grain approach for samples that are liquid at room temperature (and form a polycrystalline solid mass on cooling) is further demonstrated by investigating and solving the 1:1 co-crystal formed between hexafluorobenzene and pyridine.

Impact of Continuous Kidney Replacement Therapy and Hemoadsorption with CytoSorb on Antimicrobial Drug Removal in Critically Ill Children with Septic Shock: A Single-Center Prospective Study on a Pediatric Cohort.

Background: Extracorporeal therapies (ET) are increasingly used in pediatric settings as adjuvant therapeutic strategies for overwhelming inflammatory conditions. Although these treatments seem to be effective for removing inflammatory mediators, their influence on antimicrobials pharmacokinetic should not be neglected. Methods: A prospective observational study of children admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis/septic shock. All critically ill children received hemoadsorption treatment with CytoSorb (CS) in combination with CKRT. Therapeutic drug monitoring has been performed on 10 critically ill children, testing four antimicrobial molecules: meropenem, ceftazidime, amikacin and levofloxacin. In order to evaluate the total and isolated CKRT and CS contributions to antibiotic removal, blood samples at each circuit point (post-hemofilter, post-CS and in the effluent line) were performed. Therefore, the clearance and mass Removal (MR) of the hemofilter and CS were calculated. Results: Our preliminary report describes a different impact of CS on these target drugs removal: CS clearance was low for amikacine (6-12%), moderate for ceftazidime (43%) and moderate to high for levofloxacine (52-72%). Higher MR and clearance were observed with CKRT compared to CS. To the best of our knowledge, this is the first report regarding pharmacokinetic dynamics in critically ill children treated with CKRT and CS for septic shock.

Evaluation of Social Media and Online Utilization Among Members of the American Orthopaedic Society for Sports Medicine: Implications in Practice.

Background: Social media has the potential to act as an avenue for patient recruitment, patient and surgeon education, and expansion of the physician-patient relationship. Purpose: To evaluate the existing social media presence among members of the American Orthopaedic Society for Sports Medicine (AOSSM) to describe trends in different subgroups within the membership. Study Design: Cross-sectional study. Methods: The AOSSM database was queried for a complete membership list. Members were excluded from analysis if they were not orthopaedic sports medicine surgeons practicing in the United States. Demographic characteristics, online media profiles, and levels of online presence were evaluated, and an online media presence score was calculated. Bivariate analysis was performed to compare demographic variables and levels of online presence. Results: A total of 2870 surgeons were included in the analysis. LinkedIn was the most used platform (56%), while YouTube was the least used (10%). Surgeons in academic practice had a significantly greater overall social media presence than their private practice counterparts. Female surgeons had a more significant active online presence on Twitter, Instagram, and Facebook than male surgeons. Surgeons practicing in the Northeast had a greater social media presence than those in any other United States region, and surgeons in the earlier stages of practice (0-14 years) were more likely to utilize social media than their more senior colleagues (≥15 years of practice). On multivariate analysis, surgeons in the earlier stages of practice were more likely to have active Twitter, Instagram, and Facebook accounts, and female surgeons were more likely to have an active Facebook account. Additionally, multivariate analysis revealed that a greater number of ResearchGate publications were associated with male sex and having an academic practice. Comparatively, active Twitter and Instagram use was associated with having an academic practice. Conclusion: The most used platform in this surgeon population was LinkedIn. Orthopaedic surgeons in academic practice, female surgeons, those early in their career, and those practicing in the Northeast highlighted a subset of the sports medicine community who were more likely to have an active online presence compared to the rest of the AOSSM.

Parental anxiety in food allergy: using a cognitive behavioural therapy approach to guide early intervention.

Food allergy is a common allergic disease and often coexists with other allergic diseases such as asthma, allergic rhinitis and eczema. Parents of children and young people with food allergy commonly experience stress and anxiety and this can significantly affect their child's mental health. Interventions that incorporate approaches from cognitive behavioural therapy (CBT) can reduce stress and anxiety in parents of children and young people with food allergy and support healthy adjustment and psychological well-being in their children. However, access to psychological services is limited. This article uses reflection on a case study to illustrate the value of taking a CBT-informed intervention approach and to outline the potential role for nurses in its delivery. Research suggests that talking therapies may improve mental health and parenting behaviours in the parents of children and young people with a range of long-term conditions, so this article is also relevant to their care.

Recognizing invasive breast carcinoma of no special type with medullary pattern.

Invasive breast carcinoma of no special type (IBC-NST) with medullary pattern is an uncommon histologic type of invasive breast carcinoma. It is associated with high-grade, poorly differentiated tumor cells that form large sheets of irregular confluent tumor cells associated with a prominent lymphocytic infiltrate. Patients with IBC-NST with medullary pattern are often postmenopausal women with a high body mass index and multiparity. We report the case of a 71-year-old woman who presented for routine screening mammography and breast mass suspicious for malignancy, initially thought to be invasive ductal carcinoma with an associated prominent lymphoid infiltrate. However, it was ultimately diagnosed as IBC-NST with medullary pattern, and radiologic imaging (particularly ultrasound and mammography) along with pathology review were critical in making the diagnosis. We make the case of the importance of radiographic imaging in diagnosing this condition, as the prognosis of IBC-NST with medullary pattern is typically more favorable compared to IBC-NST.

Meniscal and Articular Cartilage Predictors of Outcome After Revision ACL Reconstruction: A 6-Year Follow-up Cohort Study.

BACKGROUND: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction. PURPOSE: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx Activity Rating Scale. Patients were followed up at 6 years and asked to complete the identical set of outcome instruments. Regression analysis assessed the meniscal and articular cartilage pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction. RESULTS: An overall 1234 patients were enrolled (716 males, 58%; median age, 26 years). Surgeons reported the pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (43%), lateral femoral condyle (29%), medial tibial plateau (11%), lateral tibial plateau (17%), patella (30%), and trochlea (21%). Six-year follow-up was obtained on 79% of the sample (980/1234). Meniscal pathology and articular cartilage pathology (medial femoral condyle, lateral femoral condyle, lateral tibial plateau, trochlea, and patella) were significant drivers of poorer patient-reported outcomes at 6 years (IKDC, KOOS, WOMAC, and Marx). The most consistent factors driving outcomes were having a medial meniscal excision (either before or at the time of revision surgery) and patellofemoral articular cartilage pathology. Six-year Marx activity levels were negatively affected by having either a repair/excision of the medial meniscus (odds ratio range, 1.45-1.72; P≤ .04) or grade 3-4 patellar chondrosis (odds ratio, 1.72; P = .04). Meniscal pathology occurring before the index revision surgery negatively affected scores on all KOOS subscales except for sports/recreation (P < .05). Articular cartilage pathology significantly impaired all KOOS subscale scores (P < .05). Lower baseline outcome scores, higher body mass index, being a smoker, and incurring subsequent surgery all significantly increased the odds of reporting poorer clinical outcomes at 6 years. CONCLUSION: Meniscal and chondral pathology at the time of revision ACL reconstruction has continued significant detrimental effects on patient-reported outcomes at 6 years after revision surgery.

Comparing the Effects of Low-Dose Ketamine, Fentanyl, and Morphine on Hemorrhagic Tolerance and Analgesia in Humans.

Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Ketamine, fentanyl, and morphine are recommended analgesics for use in the prehospital (i.e., field) setting to reduce pain. However, it is unknown whether any of these analgesics reduce hemorrhagic tolerance in humans. We tested the hypothesis that fentanyl (75 µg) and morphine (5 mg), but not ketamine (20 mg), would reduce tolerance to simulated hemorrhage in conscious humans. Each of the three analgesics was evaluated independently among different cohorts of healthy adults in a randomized, crossover (within drug/placebo comparison), placebo-controlled fashion using doses derived from the Tactical Combat Casualty Care Guidelines for Medical Personnel. One minute after an intravenous infusion of the analgesic or placebo (saline), we employed a pre-syncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (CSI), which is the sum of products of the LBNP and the duration (e.g., [40 mmHg x 3 min] + [50 mmHg x 3 min] …). Compared with ketamine (p = 0.002 post hoc result) and fentanyl (p = 0.02 post hoc result), morphine reduced the CSI (ketamine (n = 30): 99 [73-139], fentanyl (n = 28): 95 [68-130], morphine (n = 30): 62 [35-85]; values expressed as a % of the respective placebo trial's CSI; median [IQR]; Kruskal-Wallis test p = 0.002). Morphine-induced reductions in tolerance to central hypovolemia were not well explained by a prediction model including biological sex, body mass, and age (R2=0.05, p = 0.74). These experimental data demonstrate that morphine reduces tolerance to simulated hemorrhage while fentanyl and ketamine do not affect tolerance. Thus, these laboratory-based data, captured via simulated hemorrhage, suggest that morphine should not be used for a hemorrhaging individual in the prehospital setting.

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: A quality improvement study.

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy.

Integrated Osteopathic-Neurologic Examinations With Musculoskeletal Treatment: The ONE Approach.

The global burden of neurologic disorders is a leading cause of disability and death worldwide and has increased the demand for treatments and rehabilitation. Our proposed integrated osteopathic-neurologic examination (ONE) provides the physician with expanded diagnostic and point-of-care treatment modalities while allowing the physician to make a more tangible effect in patient care. By incorporating the osteopathic structural somatic examination with the complete neurologic evaluation, somatic dysfunction, occurring as a consequence or independent of neurologic injury, can be identified and treated using osteopathic manipulative techniques at time of visit. Using the proposed integrated examination, the physician can determine the interplay between structural and neurologic findings to identify patterns of change that coincide with more specific diagnoses and the chronicity of a condition. Tangible benefits from the ONE approach translate to more accurate clinical assessment and enhanced patient and physician satisfaction.

Utilizing timed categorical recall (naming US cities) for rapid bedside dementia screening.

The availability of fast validated screening for dementia is a critical clinical need to improve neurologic examination time efficiency. This study validated a 1-minute timed categorical recall (TCR) method, naming as many US cities as possible and compared TCR to the Folstein Minimental Status Exam (MMSE) as a preliminary cognitive screening tool. Random uncompensated 349 volunteers were recruited ages 18 to 97 from local free clinics, retirement homes, university faculty, and students in Lynchburg, Virginia 2015 to 2020. Participants' demographic and medical information were collected. After 1 minute preparation, participants were rapidly named as many US cities as possible until they were told to stop (1 minute). The time limitation was withheld in advance. Number of cities and organizational strategies were recorded. Folstein MMSE administration immediately after TCR was administered to 122 subjects recruited in the final 2 study years as a comparison benchmark. A multiple linear regression model and a regression tree model were used to identify important variables for the number of cities named and determine subgroups and their thresholds. TCR resulted in accuracy rate (0.80), sensitivity (0.78), and specificity (0.81). The global TCR threshold (9 cities named) is superseded by 4 subgroup thresholds, categorized by statistically important variables (age, education level, and number of states visited) as follows: For those visiting ≥8 states and 1. 18 to 71 ages with a master's degree or above, the threshold was naming 20 cities; 2. 18 to 29 ages with a bachelor's degree or below, the threshold was naming 17 cities; 3. 30 to 71 ages with a bachelor's degree or below, the threshold was naming 10 cities. For those visiting <8 states or for ages 72 to 97 (regardless of education levels and number of states visited), the threshold was naming 8 cities. American cities are common knowledge across ages and backgrounds, making it a useful bedside screen for dementia. In clinical practice, patients who report fewer cities than the threshold of 9 cities should receive further cognitive testing. If the patient meets the criteria for a subgroup, then the higher subgroup thresholds apply. TCR is a more time-efficient preliminary dementia screening tool with improved sensitivity and similar specificity compared with MMSE.

Descriptive Characteristics and Outcomes of Patients Undergoing Revision Anterior Cruciate Ligament Reconstruction With and Without Tunnel Bone Grafting.

BACKGROUND: Lytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described. PURPOSE: To describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 1234 patients who underwent rACLR were prospectively enrolled between 2006 and 2011. Baseline revision and 2-year characteristics, surgical technique, pathology, treatment, and patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale [Marx]) were collected, as well as subsequent surgery information, if applicable. The chi-square and analysis of variance tests were used to compare group characteristics. RESULTS: A total of 159 patients (13%) underwent tunnel grafting-64 (5%) patients underwent 1-stage and 95 (8%) underwent 2-stage grafting. Grafting was isolated to the femur in 31 (2.5%) patients, the tibia in 40 (3%) patients, and combined in 88 patients (7%). Baseline KOOS Quality of Life (QoL) and Marx activity scores were significantly lower in the 2-stage group compared with the no bone grafting group (P≤ .001). Patients who required 2-stage grafting had more previous ACLRs (P < .001) and were less likely to have received a bone-patellar tendon-bone or a soft tissue autograft at primary ACLR procedure (P≤ .021) compared with the no bone grafting group. For current rACLR, patients undergoing either 1-stage or 2-stage bone grafting were more likely to receive a bone-patellar tendon-bone allograft (P≤ .008) and less likely to receive a soft tissue autograft (P≤ .003) compared with the no bone grafting group. At 2-year follow-up of 1052 (85%) patients, we found inferior outcomes in the 2-stage bone grafting group (IKDC score = 68; KOOS QoL score = 44; KOOS Sport/Recreation score = 65; and Marx activity score = 3) compared with the no bone grafting group (IKDC score = 77; KOOS QoL score = 63; KOOS Sport/Recreation score = 75; and Marx activity score = 7) (P≤ .01). The 1-stage bone graft group did not significantly differ compared with the no bone grafting group. CONCLUSION: Tunnel bone grafting was performed in 13% of our rACLR cohort, with 8% undergoing 2-stage surgery. Patients treated with 2-stage grafting had inferior baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting. Patients treated with 1-stage grafting had similar baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting.

Returning to Activity After Anterior Cruciate Ligament Revision Surgery: An Analysis of the Multicenter Anterior Cruciate Ligament Revision Study (MARS) Cohort at 2 Years Postoperative.

BACKGROUND: Patients with anterior cruciate ligament (ACL) revision report lower outcome scores on validated knee questionnaires postoperatively compared to cohorts with primary ACL reconstruction. In a previously active population, it is unclear if patient-reported outcomes (PROs) are associated with a return to activity (RTA) or vary by sports participation level (higher level vs. recreational athletes). HYPOTHESES: Individual RTA would be associated with improved outcomes (ie, decreased knee symptoms, pain, function) as measured using validated PROs. Recreational participants would report lower PROs compared with higher level athletes and be less likely to RTA. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: There were 862 patients who underwent a revision ACL reconstruction (rACLR) and self-reported physical activity at any level preoperatively. Those who did not RTA reported no activity 2 years after revision. Baseline data included patient characteristics, surgical history and characteristics, and PROs: International Knee Documentation Committee questionnaire, Marx Activity Rating Scale, Knee injury and Osteoarthritis Outcome Score, and the Western Ontario and McMaster Universities Osteoarthritis Index. A binary indicator was used to identify patients with same/better PROs versus worse outcomes compared with baseline, quantifying the magnitude of change in each direction, respectively. Multivariable regression models were used to evaluate risk factors for not returning to activity, the association of 2-year PROs after rACLR surgery by RTA status, and whether each PRO and RTA status differed by participation level. RESULTS: At 2 years postoperatively, approximately 15% did not RTA, with current smokers (adjusted odds ratio [aOR] = 3.3; P = .001), female patients (aOR = 2.9; P < .001), recreational participants (aOR = 2.0; P = .016), and those with a previous medial meniscal excision (aOR = 1.9; P = .013) having higher odds of not returning. In multivariate models, not returning to activity was significantly associated with having worse PROs at 2 years; however, no clinically meaningful differences in PROs at 2 years were seen between participation levels. CONCLUSION: Recreational-level participants were twice as likely to not RTA compared with those participating at higher levels. Within a previously active cohort, no RTA was a significant predictor of lower PROs after rACLR. However, among patients who did RTA after rACLR, approximately 20% reported lower outcome scores. Most patients with rACLR who were active at baseline improved over time; however, patients who reported worse outcomes at 2 years had a clinically meaningful decline across all PROs.

Lateral Harvest of an Osseous-Based Quadriceps Tendon Autograft Results in Thinner Remaining Patellar Bone.

Background: Patellar fracture after quadriceps tendon (QT) autograft harvest for anterior cruciate ligament reconstruction (ACLR) has been reported in up to 8.8% of patients. Purpose: To determine the thickness of the remaining patellar bone across the QT graft harvest location while providing clinical guidance for safely harvesting a patellar bone block when using a QT graft in ACLR. Study Design: Descriptive laboratory study. Methods: Medial and lateral QT graft boundaries were marked using a bone saw on 13 cadaveric patellae, and 3-dimensional computed tomography models were created. After the harvest of a virtual bone block with a maximum depth of 10 mm, the thickness of the remaining bone was measured across the graft harvest location in 9 zones. The thickness of the remaining bone was analyzed according to zone, graft harvest location, and patellar facet length. Risk zones were defined as <50% total patellar depth remaining. Results: We observed substantial variability in QT bone block harvest location, in which the distance between the lateral boundary of the harvest location and the lateral patellar cortex was from 21.2% to 49.2% of the axial patellar width. There was significantly less bone remaining in the lateral columns (mean ± SD, 7.56 ± 2.19 mm) compared with the medial columns (9.83 ± 2.10 mm) of the graft harvest location (P = .028). The number of risk zones was significantly associated with distance to the lateral cortical edge, with an increase in 0.59 zones with every 1-mm decrease in distance to the lateral cortex edge (b = -0.585; R 2 = 0.620; P = .001). With every 1-mm increase in the distance of the lateral cortex to the lateral graft boundary, the thickness of bone remaining in the lateral column increased by 0.412 mm (P < .001). No risk zones were encountered when the lateral boundary of the harvest location was created 18.9 mm from the lateral edge of the patella or 43% of the total patellar width from the lateral edge. Conclusion: Harvest of a more laterally based QT autograft bone block resulted in thinner remaining patellar thickness, increasing the potential of encountering a risk zone for fracture. Clinical Relevance: Care should be taken to avoid harvesting the patellar bone block too laterally during ACLR.

Patients Follow 3 Different Rate-of-Recovery Patterns After Anterior Cruciate Ligament Reconstruction Based on International Knee Documentation Committee Score.

PURPOSE: To determine whether subgroups of patients exist based on the rate-of-recovery pattern of International Knee Documentation Committee (IKDC) scores after anterior cruciate ligament reconstruction (ACLR) and to determine clinical predictors for these subgroups. METHODS: Patients who underwent primary or revision ACLR at a single institution from January 2014 to January 2019 were identified. Latent class growth analyses and growth mixture models (GMMs) with 1 to 6 classes were used to identify subgroups of patients based on functional rate-of-recovery patterns by use of preoperative, 1-year postoperative, and 2-year postoperative IKDC scores. RESULTS: A total of 245 patients who underwent ACLR were included in the analysis. A 3-class GMM was chosen as the final model after 6 different models were run. Class 1, showing improvement from preoperatively to 1-year follow-up, with sustained improvement from 1 to 2 years postoperatively, constituted 77.1% of the study population (n = 189), whereas class 2, showing functional improvement between 1- and 2-year follow-up, was the smallest class, constituting 10.2% of the study population (n = 25), and class 3, showing slight improvement at 1-year follow-up, with a subsequent decline in IKDC scores between 1- and 2-year follow-up, constituted 12.7% of the study population (n = 31). Revision surgery (P = .005), a psychiatric history (P = .025), preoperative chronic knee pain (P = .024), and a subsequent knee injury within the follow-up period (P = .011) were the predictors of class 2 and class 3 rate-of-recovery patterns. Patient demographic characteristics, graft type, and concomitant ligament, meniscus, or cartilage injury at the time of surgery were not associated with the different recovery patterns described in this study. CONCLUSIONS: Patients may follow different rate-of-recovery patterns after ACLR. By use of the GMMs, 3 different rate-of-recovery patterns based on IKDC scores were identified. Although most patients follow a more ideal rate-of-recovery pattern, fewer patients may follow less favorable patterns. Revision surgery, a history of psychiatric illness, preoperative chronic knee pain, and a subsequent knee injury within the follow-up period were predictive of less favorable rate-of-recovery patterns. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Establishing Clinically Significant Outcomes After Anterior Cruciate Ligament Reconstruction in Pediatric Patients.

PURPOSE: The purpose of this study was to establish clinically significant outcome values for the minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) after anterior cruciate ligament reconstruction (ACLR) in the pediatric and adolescent populations and to assess factors that were associated with achieving these outcomes. METHODS: Patients between the age of 10 to 21 who underwent ACLR between 2016 and 2018 were identified and patient-reported outcomes (PROs) were collected preoperatively and postoperatively. Intraoperative variables collected included graft choice, graft size (diameter), graft fixation method, and concomitant procedures. PROs collected for analysis were the International Knee Documentation Committee Score (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). MCID and PASS were calculated using receiver operating characteristic with area under the curve analyses for delta (ie, baseline-to-postoperative change) and absolute postoperative PRO scores, respectively. RESULTS: A total of 59 patients were included in the analysis. Of the entire study population, 53 (89.8%) reported satisfaction with their surgical outcome. The established MCID threshold values based on the study population were 33.3 for IKDC, 28.6 for (KOOS) Symptoms, 19.4 for Pain, 2.9 for activities of daily living (ADL), 45.0 for Sport, and 25.0 for Quality of Life (QoL). Postoperative scores greater than the following values corresponded to the PASS: 80.5 for IKDC, 75.0 (KOOS) Symptoms, 88.9 for Pain, 98.5 for ADL, 75.0 for Sport, and 68.8 for QoL. CONCLUSION: Clinically meaningful outcomes including MCID and PASS were established for pediatric ACLR surgery using selected PRO measures, IKDC, and KOOS. Patient age, sex, graft type, and graft size were not associated with greater achievement of these outcomes. In contrast, collision sports, fixed-object high-impact rotational landing sports, and concomitant meniscectomy surgery were associated with a decreased likelihood of achieving clinically significant improvement. However, findings must be interpreted with caution due to limitations in follow-up and sample size. LEVEL OF EVIDENCE: Level IV: case series.

Delaying ACL reconstruction beyond 6 months from injury impacts likelihood for clinically significant outcome improvement.

BACKGROUND: The effect of surgical latency on outcomes of anterior cruciate ligament reconstruction (ACLR) is a topic that is heavily debated. Some studies report increased benefit when time from injury to surgery is decreased while other studies report no benefit. The purpose of our analysis was to compare achievement of clinically significant outcomes (CSOs) in patients with greater than six months of time from injury to ACLR to those with less than or equal to six months of time to surgery. METHODS: Patients undergoing primary ACLR between January 2017 and January 2018 with minimum one year follow-up were included. International Knee Documentation Committee (IKDC) score and Knee Injury and Osteoarthritis Outcomes Score (KOOS) were collected. Multivariate logistic regression was performed for outcome achievement and risk of revision ACLR and Weibull parametric survival analysis was performed for relative time to outcome achievement. The level of significance was set at α = 0.05. RESULTS: 379 patients were included of which, 140 patients sustained ACL injury greater than six months prior to surgery. This group of patients experienced reduced likelihood to achieve patient-acceptable symptomatic state (PASS) on the IKDC (p = 0.03), KOOS Pain (p = 0.01) and a greater likelihood to undergo revision ACLR (p = 0.001). There was no impact of surgical timing on minimal clinically important difference (MCID). CONCLUSION: Patients with greater than 6 months from injury to ACLR reported reduced likelihood to achieve CSOs, delayed achievement of CSOs, and increased rates of revision surgery.