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In: Nature Genetics, Springer Science and Business Media LLC, Vol. 54, No. 4 ( 2022-04), p. 412-436

Abstract: Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Type of Medium: Online Resource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/s41588-022-01024-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 1494946-5

SSG: 12

In: Orthopaedic Journal of Sports Medicine, SAGE Publications, Vol. 11, No. 2 ( 2023-02-01), p. 232596712311546-

Abstract: Gymnastics requires intense year-round upper and lower extremity strength training typically starting from an early age. As such, the injury patterns observed in these athletes may be unique. Purpose: To characterize the types of injuries and provide return-to-sport data in male and female collegiate gymnasts. Study Design: Descriptive epidemiology study. Methods: A conference-specific injury database was utilized to perform a retrospective review of injuries for male and female National Collegiate Athletic Association (NCAA) Division I gymnasts within the Pacific Coast Conference between 2017 and 2020 (N = 673 gymnasts). Injuries were stratified by anatomic location, sex, time missed, and injury diagnoses. Relative risk (RR) was used to compare results between sexes. Results: Of the 673 gymnasts, 183 (27.2%) experienced 1093 injuries during the study period. Injuries were sustained in 35 of 145 male athletes (24.1%) as compared with 148 of 528 female athletes (28.0%; RR, 0.86 [95% CI, 0.63-1.19]; P = .390). Approximately 66.1% (723/1093) of injuries occurred in a practice setting, compared with 84 of 1093 injuries (7.7%) occurring during competition. Overall, 417 of 1093 injuries (38.2%) resulted in no missed time. Shoulder injuries and elbow/arm injuries were significantly more common in male versus female athletes (RR, 1.99 [95% CI, 1.32-3.01] , P = .001; and RR, 2.08 [95% CI, 1.05-4.13], P = .036, respectively). In total, 23 concussions affected 21 of 673 athletes (3.1%); 6 concussions (26.1%) resulted in the inability to return to sport during the same season. Conclusion: For the majority of musculoskeletal injuries, the gymnasts were able to return to sport during the same season. Male athletes were more likely to experience shoulder and elbow/arm injuries, likely because of sex-specific events. Concussions occurred in 3.1% of the gymnasts, highlighting the need for vigilant monitoring. This analysis of the incidence and outcomes of injuries observed in NCAA Division I gymnasts may guide injury prevention protocols as well as provide important prognostic information.

Type of Medium: Online Resource

ISSN: 2325-9671 , 2325-9671

URL: Article

DOI: 10.1177/23259671231154618

Language: English

Publisher: SAGE Publications

Publication Date: 2023

detail.hit.zdb_id: 2706251-X

SSG: 31

In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 15 ( 2005-08-01), p. 5515-5525

Abstract: Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell–mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme. Experimental Design: Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 μg per injection) of acid-eluted autologous tumor peptides. All patients had histologically proven glioblastoma multiforme. Three biweekly intradermal vaccinations were given; and patients were monitored for adverse events, survival, and immune responses. The follow-up period for this trial was almost 5 years. Results: Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic antitumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor β2 (TGF-β2). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated with TGF-β2 expression within the tumors and positively correlated with clinical survival (P = 0.047). Conclusions: Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with low TGF-β2 expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell–based vaccines.

Type of Medium: Online Resource

ISSN: 1078-0432 , 1557-3265

URL: Article

DOI: 10.1158/1078-0432.CCR-05-0464

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2005

detail.hit.zdb_id: 1225457-5

detail.hit.zdb_id: 2036787-9

In: Journal of Cartilage & Joint Preservation, Elsevier BV, Vol. 2, No. 2 ( 2022-06), p. 100058-

Type of Medium: Online Resource

ISSN: 2667-2545

URL: Article

DOI: 10.1016/j.jcjp.2022.100058

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 3101390-9

In: Clinical Orthopaedics & Related Research, Ovid Technologies (Wolters Kluwer Health), Vol. 470, No. 3 ( 2012-03), p. 677-683

Type of Medium: Online Resource

ISSN: 0009-921X

URL: Article

DOI: 10.1007/s11999-011-2172-8

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2012

detail.hit.zdb_id: 2018318-5

In: JBJS Essential Surgical Techniques, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 4 ( 2021-10-12)

Abstract: Although most patients who undergo anterior cruciate ligament (ACL) reconstruction achieve long-term functional stability and symptom relief, graft rupture rates range from 2% to 10% 1,2 . A small subset of these patients require a 2-stage revision ACL reconstruction because of tunnel osteolysis or tunnel malposition that will interfere with the planned revision tunnel placement 3 . In the present article, we describe the hybrid use of arthroscopically delivered injectable allograft matrix in the femur and pre-shaped bone dowels in the tibia for the treatment of lower-extremity bone deficiencies. Description: After induction of anesthesia, approximately 60 cc of bone marrow aspirate is harvested from the anterior iliac crest with use of sterile techniques and is processed to obtain bone marrow aspirate concentrate. Routine diagnostic knee arthroscopy is performed via the standard anterolateral and anteromedial portals. Any additional intra-articular pathology is addressed, followed by excision of the remnant graft material, removal of existing femoral hardware as needed, and exposure of the existing bone tunnels. The femoral tunnel is debrided arthroscopically, removing all soft-tissue remnants. The existing tibial tunnel is exposed via the previous anteromedial tibial incision when possible. Again, any existing tibial hardware is removed. The tibial tunnel is then prepared with use of a combination of sequential reaming and dilation. A shaver and curets are utilized to debride the sclerotic walls of the tunnel and remove the remnant graft material. A cannulated allograft bone dowel is then impacted into place over a guidewire, ensuring that the graft is not proud within the joint space. An injectable bone allograft matrix composite is prepared by manually mixing 5 mL of StimuBlast demineralized bone matrix (Arthrex) and 5 mL of FlexiGraft cortical fibers (Arthrex), along with the previously obtained bone marrow aspirate concentrate. Under dry arthroscopy, this bone graft is delivered into the femoral tunnel via a cannula with use of the anteromedial portal. Finally, a Freer elevator is used to contour the graft at the aperture of the tunnel. Graft osteointegration is mandatory prior to proceeding with the second stage of the procedure. Typically, a minimum 3-month follow-up is necessary to confirm adequate graft incorporation on computed tomography. Alternatives: As an alternative to the 2-stage procedure, previous studies have suggested the use of a single-stage revision utilizing cylindrical allografts or multiple “stacked screws.” 4–6 In addition, a number of bone allograft and autograft options have been described. Autologous bone graft can be harvested from the ipsilateral iliac crest or proximal aspect of the tibia with use of a variety of techniques 7–10 . Allograft bone options include cancellous bone chips and commercially available bone matrices or dowels 11–14 . Finally, another viable option is calcium phosphate bone graft substitutes 15 . There is a paucity of high-quality studies comparing available bone graft materials for revision ACL reconstruction; thus, no consensus exists regarding the optimal choice 16 . Rationale: A 2-stage approach is typically indicated for cases that demonstrate tunnel enlargement ( 〉 12 mm) that would compromise graft fixation or non-anatomic tunnel placement that will interfere with placement of the revision tibial tunnel 3 . The aim of the first stage is to re-establish adequate bone stock to optimize future tunnel placement and healing of the ACL graft during the second stage. We believe that this 2-stage approach is a reliable and safe method of treating enlarged, irregularly shaped bone tunnel defects while minimizing the risk of complications. Furthermore, the use of allograft material avoids the donor-site morbidity and volume limitations associated with the use of autograft bone. In the case of the femoral tunnel, the injectable bone graft composite has the advantage of being easily delivered arthroscopically while completely filling irregularly shaped tunnels. The use of bone marrow aspirate concentrate may improve the rate of graft healing as well as a hydrating substance to reduce viscosity and facilitate the flow of the bone graft material through the cannula 16,17 . For the tibia, especially in cases of lengthy tibial bone deficiencies, allograft bone dowels are commercially available off-the-shelf in a variety of different lengths and diameters to allow for adequate fill of bone defects. Expected Outcomes: It is well known that outcomes following revision ACL reconstruction are inferior to those following primary ACL reconstruction, with a number of variables, beyond those associated with the surgical technique, influencing clinical outcomes 18 . Few studies have reported on the results of 2-stage revision ACL reconstruction with use of allograft bone; however, a high rate of allograft bone integration and improved bone quality at the time of revision ACL reconstruction have been reported 13 . Moreover, Mitchell et al. reported no differences in either subjective outcomes or failure rates between the 1-stage and 2-stage revision ACL reconstruction groups 11 . Important Tips: Utilize computed tomography for preoperative assessment and measurement of the extent of osteolysis. If possible, obtain the operative report for the index ACL procedure in order to identify any preexisting hardware and to obtain any instrumentation that may be needed to facilitate hardware removal. Multiple bone dowel sizes are available off the shelf. A 70° arthroscope can aid in visualization of the entire tibial and femoral tunnel. Although the bone graft matrix can be injected while the joint is filled with irrigation fluid, we find it easier to administer the graft under dry arthroscopic conditions. Place the scope inside the tibial tunnel to confirm appropriate removal of soft tissue and hardware. Circumferential native cancellous bone should be visualized. It is acceptable to retain previous hardware if it does not interfere with the new tunnel placement. Utilize prior incisions to access the tibial tunnel. Do not underestimate the amount of bone graft needed for each tunnel. Avoid excessive force during impaction of the dowels. Acronyms and Abbreviations: ACLR = Anterior cruciate ligament reconstruction BMAC = Bone marrow aspirate concentrate MRI = Magnetic resonance imaging CT = Computed tomography BTB = Bone-patellar tendon-bone DVT = Deep vein thrombosis ROM = Range of motion

Type of Medium: Online Resource

ISSN: 2160-2204

URL: Article

DOI: 10.2106/JBJS.ST.20.00055

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2021

detail.hit.zdb_id: 2747088-X

In: Orthopaedic Journal of Sports Medicine, SAGE Publications, Vol. 10, No. 7 ( 2022-07-01), p. 232596712211102-

Abstract: There are few data on injuries suffered by collegiate water polo athletes. Purpose: To describe the epidemiology of injuries suffered by National College Athletic Association (NCAA) male and female water polo players by using injury surveillance data over a 5-year period. Study Design: Descriptive epidemiology study. Methods: Deidentified data on all water polo injuries and illnesses recorded in the Pac-12 Sports Injury Research Archive from July 2016 through June 2021 were obtained and analyzed. Three men’s and 4 women’s teams were observed for the entire 5-year period, and 1 men’s and 1 women’s team was observed from July 2018 through June 2021. Results: During the observation period, 729 injuries were recorded in the database, with no differences in overall injury rates between male and female athletes (relative risk [RR] = 1.0; 95% CI, 0.9-1.2); 33.7% of injuries required a physician encounter, and 3.6% required surgery. The shoulder was the most injured body part, making up 20.6% of all injuries, followed by the head/face (18.8%) and hand/wrist/forearm (11.7%). Shoulder tendinopathy was the most common shoulder injury diagnosis (4.5% of all injuries). Concussion was the most common injury diagnosis overall, making up 11.4% of injuries, and 81.9% of concussions occurred outside of competition. Male athletes were significantly more likely than female athletes to have a concussion in an off-season practice (RR, 3.25; 95% CI, 1.2-8.8) and via contact with another player (RR, 2.9; 95% CI, 1.3-6.4). Half of the 26 surgical procedures occurring over the observation period were for chronic joint trauma of the groin/hip/pelvis/buttock, with 9 of those 13 being for femoroacetabular impingement specifically. Conclusion: Among NCAA water polo athletes, the shoulder was the most injured body part; however, shoulder injuries rarely required missed time from sport or necessitated surgical intervention. Concussions were the most common injury diagnosis, had the worst return-to-play outcomes among common diagnoses, and were mostly sustained outside of competition. Femoroacetabular impingement was found to be the dominant diagnosis for which surgical intervention was required.

Type of Medium: Online Resource

ISSN: 2325-9671 , 2325-9671

URL: Article

DOI: 10.1177/23259671221110208

Language: English

Publisher: SAGE Publications

Publication Date: 2022

detail.hit.zdb_id: 2706251-X

SSG: 31

In: Orthopaedic Journal of Sports Medicine, SAGE Publications, Vol. 11, No. 5 ( 2023-05), p. 232596712311691-

Abstract: The coronavirus disease 2019 (COVID-19) pandemic significantly disrupted athletic activities, including those in the Pacific 12 (Pac-12) Conference of the National Collegiate Athletic Association. It is currently unknown how the disruption in training and competition impacted athletes’ risk of injury upon resumption of activities. Purpose: To describe and compare the rate, timing, mechanism, and severity of injuries among collegiate athletes across multiple sports in the Pac-12 Conference before and after the COVID-19 pandemic–associated hiatus of intercollegiate athletic activities. Study Design: Descriptive epidemiology study. Methods: Descriptive and injury data among intercollegiate athletes from both the season before the hiatus and the season after the hiatus were acquired from the Pac-12 Health Analytics Program database. Injury elements (timing of injury onset, injury severity, mechanism, recurrence, outcome, need for procedural intervention, and event segment during which the injury took place) were compared by time using the chi-square test and a multivariate logistic regression model. Subgroup analyses were performed on knee and shoulder injuries among athletes participating in sports with traditionally high rates of knee and shoulder injuries. Results: A total of 12,319 sports-related injuries across 23 sports were identified, with 7869 pre-hiatus injuries and 4450 post-hiatus injuries. There was no difference in the overall incidence of injury between the pre-hiatus and post-hiatus seasons. However, the proportion of noncontact injuries was higher in the post-hiatus season for football, baseball, and softball players, and the proportion of nonacute injuries in the post-hiatus season was higher among football, basketball, and rowing athletes. Finally, the overall proportion of injuries sustained by football players in the final 25% of competition or practice was higher in the post-hiatus season. Conclusion: Athletes competing in the post-hiatus season were observed to have higher rates of noncontact injuries and injuries sustained in the final 25% of competition. This study demonstrates that the COVID-19 pandemic has had varied effects on athletes from different sports, suggesting that many factors must be considered when designing return-to-sports programs for athletes after an extended absence from organized training.

Type of Medium: Online Resource

ISSN: 2325-9671 , 2325-9671

URL: Article

DOI: 10.1177/23259671231169188

Language: English

Publisher: SAGE Publications

Publication Date: 2023

detail.hit.zdb_id: 2706251-X

SSG: 31

In: The American Journal of Sports Medicine, SAGE Publications, Vol. 46, No. 1 ( 2018-01), p. 163-170

Abstract: A hamstring autograft is commonly used in anterior cruciate ligament (ACL) reconstruction (ACLR); however, there is evidence to suggest that the tendons harvested may contribute to medial knee instability. Hypothesis: We tested the hypothesis that the gracilis (G) and semitendinosus (ST) tendons significantly contribute to sagittal, coronal, and/or rotational knee stability in the setting of ACLR with a concurrent partial medial collateral ligament (MCL) injury. Study Design: Controlled laboratory study. Methods: Twelve human cadaveric knees were subject to static forces applied to the tibia including an anterior-directed force as well as varus, valgus, and internal and external rotation moments to quantify laxity at 0°, 30°, 60°, and 90° of flexion. The following ligament conditions were tested on each specimen: (1) ACL intact/MCL intact, (2) ACL deficient/MCL intact, (3) ACL deficient/partial MCL injury, and (4) ACLR/partial MCL injury. To quantify the effect of muscle loads, the quadriceps, semimembranosus, biceps femoris, sartorius (SR), ST, and G muscles were subjected to static loads. The loads on the G, ST, and SR could be added or removed during various test conditions. For each ligament condition, the responses to loading and unloading the G/ST and SR were determined. Three-dimensional positional data of the tibia relative to the femur were recorded to determine tibiofemoral rotations and translations. Results: ACLR restored anterior stability regardless of whether static muscle loads were applied. There was no significant increase in valgus motion after ACL transection. However, when a partial MCL tear was added to the ACL injury, there was a 30% increase in valgus rotation ( P 〈 .05). ACLR restored valgus stability toward that of the intact state when the G/ST muscles were loaded. A load on the SR muscle without a load on the G/ST muscles restored 19% of valgus rotation; however, it was still significantly less stable than the intact state. Conclusion: After ACLR in knees with a concurrent partial MCL injury, the absence of loading on the G/ST did not significantly alter anterior stability. Simulated G/ST harvest did lead to increased valgus motion. These results may have important clinical implications and warrant further investigation to better outline the role of the medial hamstrings, particularly among patients with a concomitant ACL and MCL injury. Clinical Relevance: A concurrent ACL and MCL injury is a commonly encountered clinical problem. Knowledge regarding the implications of hamstring autograft harvest techniques on joint kinematics may help guide management decisions.

Type of Medium: Online Resource

ISSN: 0363-5465 , 1552-3365

URL: Article

DOI: 10.1177/0363546517732743

Language: English

Publisher: SAGE Publications

Publication Date: 2018

detail.hit.zdb_id: 2063945-4

SSG: 31

In: The American Journal of Sports Medicine, SAGE Publications, Vol. 49, No. 14 ( 2021-12), p. 3887-3897

Abstract: The ability to predict meniscus tear reparability based on preoperative magnetic resonance imaging (MRI) is desirable for postoperative planning; however, the accuracy of predictive methods varies widely within the orthopaedic and radiology literature. Purpose/Hypothesis: The purpose was to determine if the higher resolution offered by 3-T MRI improves the accuracy of predicting reparability compared with previous investigations using 1.5-T MRI. Our hypothesis was that a higher field strength of 3-T MRI would result in improved reliability assessments and predictions of meniscus tear reparability compared with previous studies utilizing a 1.5-T MRI platform. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 44 patients who underwent meniscus repair were matched by age, sex, and body mass index to 43 patients who underwent partial meniscectomy. Overall, 2 orthopaedic surgeons and 2 musculoskeletal radiologists independently and blindly reviewed the preoperative MRI scans for all 87 patients. For each meniscus tear, reviewers evaluated the following criteria: tear pattern, tear length, tear distance from the meniscocapsular junction, tear thickness, and integrity of any inner meniscal fragment. The resultant data were then applied to 5 different approaches for predicting meniscal reparability. Results: The accuracy for all examined prediction methods was poor, ranging from 55% (3-point method) to 72% (classification tree method) among all reviewers. Interobserver reliability for examined criteria was also poor, with kappa values ranging from 0.07 (inner meniscal fragment status) to 0.40 (tear pattern). Conclusion: MRI continues to be a poor predictor of meniscus tear reparability as assessed by arthroscopic criteria, even when using higher resolution 3-T scanners. Interobserver reliability in this setting can be poor, even among experienced clinicians.

Type of Medium: Online Resource

ISSN: 0363-5465 , 1552-3365

URL: Article

DOI: 10.1177/03635465211052526

Language: English

Publisher: SAGE Publications

Publication Date: 2021

detail.hit.zdb_id: 2063945-4

SSG: 31