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The purpose of this study is to compare failure rates among different techniques of primary anterior cruciate ligament (ACL) repair for the treatment of proximal ACL ruptures. Meta-analysis and systematic review were completed, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies from Embase, Cochrane, and PubMed published between June 2011 and June 2022 reporting outcomes of primary ACL repair on proximal tears with a minimum two-year follow-up were included. Primary ACL repair was divided into dynamic, static, and non-augmented repair. The primary outcome was failure rates, and the secondary outcomes included patient-reported outcomes (PROs) and anterior tibial stability (ATT). Eighteen studies on primary ACL repair were included, with a total of 614 patients (ages ranging from 6 to 65, 60% male). Only two studies were level 1 randomized controlled clinical trials. The static repair had a failure rate of 33 out of 261 (12.6%), non-augmented was 17 out of 179 (9.4%), and dynamic repair was 31 out of 174 (17.8%); no statistically significant difference was found comparing the failure rates (p = 0.090). PROs using the International Knee Documentation Committee (IKDC) and Lysholm scores had weighted averages of 91.7 (95% confidence interval (CI): 89.6-93.8) and 94.7 (95% CI: 92.7-96.7), respectively. ATT had a weighted average of 1.668 mm (95% CI: 1.002-2.334). The primary findings of this paper include a 12.6% combined failure rate for primary proximal ACL repair with no significant difference in failure rate or PROs when accounting for the methodology of repair at a minimum two-year follow-up. It is important to note the lack of high-quality randomized controlled trials, the heterogeneity of included studies, and the lack of long-term data. Despite these limitations, the findings of the current analysis suggest that primary repair may be a useful treatment option for indicated candidates with proximal ACL ruptures. Further long-term and higher-quality comparative studies on ACL reconstruction are warranted.
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PURPOSE: To describe the currently available literature reporting clinical outcomes for bioactive and bioinductive implants in sports medicine. METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of 4 databases was completed to identify eligible studies. Inclusion criteria were studies using bioactive or bioinductive implants in human clinical studies for sports medicine procedures. Data were extracted and reported in narrative form, along with study characteristics. RESULTS: In total, 145 studies were included involving 6,043 patients. The majority of included studies were level IV evidence (65.5%), and only 36 included a control group (24.8%). Bioactive materials are defined as any materials that stimulate an advantageous response from the body upon implantation, whereas bioinductive materials provide a favorable environment for a biological response initiated by the host. Bioactivity can speed healing and improve clinical outcome by improving vascularization, osteointegration, osteoinduction, tendon healing, and soft-tissue regeneration or inducing immunosuppression or preventing infection. The most common implants reported were for knee (67.6%, primarily cartilage [most commonly osteochondral defects], anterior cruciate ligament, and meniscus), shoulder (16.6%, primarily rotator cuff), or ankle (11.7%, primarily Achilles repair). The most common type of implant was synthetic (44.1%), followed by autograft (30.3%), xenograft (16.6%), and allograft (9.0%). In total, 69% of implants were standalone treatments and 31% were augmentation. CONCLUSIONS: The existing bioactive and bioinductive implant literature in sports medicine is largely composed of small, low-level-of-evidence studies lacking a control group. CLINICAL RELEVANCE: Before bioactive implants can be adapted as a new standard of care, larger, comparative clinical outcome studies with long-term follow-up are essential.
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Protocoles de polychimiothérapie antinéoplasique , Transplantation de cellules souches hématopoïétiques , Lymphome T périphérique , Conditionnement pour greffe , Transplantation autologue , Humains , Transplantation de cellules souches hématopoïétiques/méthodes , Lymphome T périphérique/thérapie , Conditionnement pour greffe/méthodes , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/pharmacocinétique , Mâle , Adulte d'âge moyen , Femelle , Cytarabine/administration et posologie , Cytarabine/pharmacocinétique , Cytarabine/usage thérapeutique , Carmustine/administration et posologie , Carmustine/pharmacocinétique , Carmustine/usage thérapeutique , Adulte , Melphalan/administration et posologie , Melphalan/usage thérapeutique , Melphalan/pharmacocinétique , Sujet âgéRÉSUMÉ
Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients.
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Protocoles de polychimiothérapie antinéoplasique , Composés du bore , Glycine , Lénalidomide , Lymphome folliculaire , Rituximab , Humains , Composés du bore/usage thérapeutique , Composés du bore/administration et posologie , Composés du bore/effets indésirables , Glycine/analogues et dérivés , Glycine/usage thérapeutique , Glycine/effets indésirables , Glycine/administration et posologie , Rituximab/effets indésirables , Rituximab/usage thérapeutique , Rituximab/administration et posologie , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Lénalidomide/administration et posologie , Lénalidomide/usage thérapeutique , Lénalidomide/effets indésirables , Adulte , Lymphome folliculaire/traitement médicamenteux , Lymphome folliculaire/mortalité , Résultat thérapeutique , Lymphome malin non hodgkinien/traitement médicamenteux , Lymphome malin non hodgkinien/mortalité , Lymphome malin non hodgkinien/anatomopathologie , Sujet âgé de 80 ans ou plusRÉSUMÉ
Understanding the preoperative risk factors for successful rotator cuff repair (RCR) and ways to optimize these factors is an evolving area of study. The Rotator Cuff Healing Index and other proxy risk factors for failed rotator cuff healing have implicated significant fatty infiltration, muscular atrophy, advanced chronological age, tear size and retraction, and ultimately, osteoporosis. Although structural (or biological) augmentation and tendon transfer have been proposed as solutions for the alarmingly high rate of failure after primary RCR, other options may preferentially focus on the enthesis and underlying osseous footprint. Currently, bisphosphonates are frequently used in the treatment of osteoporosis and prevention of fragility fractures. However, burgeoning evidence suggests that postoperative zoledronic acid may have clinical utility after rotator cuff and other tendon repairs. In the cost-conscious world of evidence-based medicine, the added economic burden of additional medications and office visits may or may not improve patient outcomes-much less confer added value. Our advice to fellow shoulder surgeons: Wait for further information, but continue to holistically consider and optimize risk factors for poor soft-tissue healing. Although the addition of postoperative bisphosphonates may improve suture anchor fixation and promote a better foundation for healing, it will not immediately transform your RCR success rates.
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Ostéoporose post-ménopausique , Ostéoporose , Lésions de la coiffe des rotateurs , Femelle , Humains , Coiffe des rotateurs/chirurgie , Acide zolédronique/usage thérapeutique , Lésions de la coiffe des rotateurs/traitement médicamenteux , Lésions de la coiffe des rotateurs/chirurgie , Ostéoporose post-ménopausique/traitement médicamenteux , Tendons/chirurgie , Ostéoporose/complications , Ostéoporose/traitement médicamenteux , Résultat thérapeutique , ArthroscopieRÉSUMÉ
OBJECTIVES: Chronic exertional compartment syndrome (CECS) can be diagnosed either clinically or with intra-compartmental pressure monitor measurements and can be treated surgically or conservatively. METHODS: A systematic review was performed on diagnostic and treatment modalities for CECS. Included studies were those that reported both their specific diagnostic modality and treatment regimens. Both surgical and conservative treatment strategies were considered. Demographic variables, diagnostic modalities, patient satisfaction and return to sport, the number of surgical incisions used for the anterior compartment fasciotomy, and the specific conservative treatment regimens were also recorded. Diagnostic modalities were grouped into one of three groups: 1) static compartment pressure monitor, 2) dynamic pressure monitoring, and 3) strictly clinical diagnosis. RESULTS: The literature search identified 373 studies, of which 29 were included for final analysis. In total, there were 1270 total patients. Twenty-four studies used static compartment pressure monitors, 5 studies used dynamic pressure monitors and 2 studies used a strictly clinical diagnosis. Surgical management with fasciotomy was performed in 25 studies with a total of 1018 patients, while conservative management was used in 252 patients in 9 studies (5 studies included surgical and conservative treatments). Among surgical studies, 15 used a single-incision technique for anterior compartment fasciotomy, while 6 used a 2-incision technique. The reported satisfaction after fasciotomy was 42-94% while the return to sport was 26-100%. The reported return to sport in conservative management studies was 25-35%. CONCLUSION: This systematic review found that the majority of clinical reports utilize static compartment pressure measurements to diagnose CECS, with fewer studies using dynamic intra-compartment pressure monitors. Additionally, surgical fasciotomy using a single-incision technique was the most common treatment strategy for anterior compartment CECC, with some studies reporting success with the two-incision technique. STUDY DESIGN: Systematic review, level 4.
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Syndrome des loges , Sports , Humains , Syndrome de loge chronique d'effort , Fasciotomie/méthodes , Maladie chronique , Syndrome des loges/diagnostic , Syndrome des loges/chirurgieRÉSUMÉ
BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is increasingly used as a treatment modality for various pathologies. The purpose of this review is to identify preoperative risk factors associated with loss of internal rotation (IR) after RTSA. METHODS: A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ovid MEDLINE, Ovid Embase, and Scopus were queried. The inclusion criteria were as follows: articles in English language, minimum 1-year follow-up postoperatively, study published after 2012, a minimum of 10 patients in a series, RTSA surgery for any indication, and explicitly reported IR. The exclusion criteria were as follows: articles whose full text was unavailable or that were unable to be translated to English language, a follow-up of less than 1 year, case reports or series of less than 10 cases, review articles, studies in which tendon transfers were performed at the time of surgery, procedures that were not RTSA, and studies in which the range of motion in IR was not reported. RESULTS: The search yielded 3792 titles, and 1497 duplicate records were removed before screening. Ultimately, 16 studies met the inclusion criteria with a total of 5124 patients who underwent RTSA. Three studies found that poor preoperative functional IR served as a significant risk factor for poor postoperative IR. Eight studies addressed the impact of subscapularis, with 4 reporting no difference in IR based on subscapularis repair and 4 reporting significant improvements with subscapularis repair. Among studies with sufficient power, BMI was found to be inversely correlated with degree of IR after RTSA. Preoperative opioid use was found to negatively affect IR. Other studies showed that glenoid retroversion, component lateralization, and individualized component positioning affected postoperative IR. CONCLUSIONS: This study found that preoperative IR, individualized implant version, preoperative opioid use, increased body mass index and increased glenoid lateralization were all found to have a significant impact on IR after RTSA. Studies that analyzed the impact of subscapularis repair reported conflicting results.
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Arthroplastie de l'épaule , Articulation glénohumérale , Humains , Arthroplastie de l'épaule/effets indésirables , Arthroplastie de l'épaule/méthodes , Articulation glénohumérale/chirurgie , Analgésiques morphiniques , Résultat thérapeutique , Arthroplastie , Amplitude articulaire , Études rétrospectivesRÉSUMÉ
BACKGROUND: Acid-fast bacilli(AFB) and fungi are generally slow-growing, difficult to culture, and rarely the cause of infection. The goal of this study was to evaluate the value of routinely obtaining AFB and fungal cultures in foot and ankle surgery at a US hospital. METHODS: A retrospective review was conducted to determine the number of positive AFB and fungal cultures out of the total number of foot and ankle samples tested. Between 2014 and 2019, patients who underwent surgery for a foot and ankle infection for soft tissue infection, septic arthritis, infectious postoperative complications were identified. Charts were reviewed to identify the results of the microbiological tests performed. To determine the value of running AFB and fungal cultures, the costs of each were provided by the microbiology lab at our institution. RESULTS: Of the 322 patient charts reviewed, there were 434 AFB and 525 fungal cultures performed. None of these cultures were indicated to be positive for AFB (0%), and 22 (4.19%) were positive for fungi. The total labor and material costs were calculated to be $38 767. The AFB cultures cost $23 967, the positive fungal cultures cost $2371, and the negative fungal cultures cost $36 395.36. CONCLUSION: This 322-case series of surgically managed foot and ankle infections showed 0% and 4.1% positivity rates of AFB and fungal cultures, respectively. Additionally, only 20% of cases with positive cultures were identified as pathologic requiring antifungal treatment. Further analysis is needed to determine best practices for obtaining vs declining to culture for AFB or fungal species, including assessing patient outcomes in the series of culture-positive(fungal-only) cases. Our results suggest that in our clinical setting of a US hospital system, routine fungal and AFB cultures may not be necessary but should be considered for chronic/recalcitrant infections, immunocompromised patients, and those with high surgeon suspicion. LEVEL OF EVIDENCE: Level IV, case series.
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Arthrite infectieuse , Infections des tissus mous , Humains , Cheville/chirurgie , Hôpitaux , Études rétrospectivesRÉSUMÉ
Recently there has been a growing interest in evaluating body composition as a marker for prognosis in cancer patients. The association of body composition parameters and outcomes has not been deeply investigated in patients with autologous hematopoietic stem cell transplantation (HSCT) recipients with non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of 264 NHL patients who received autologous HSCT. PreHSCT abdominal CT scans at the levels of L3 were assessed for body composition measures. We evaluated sarcopenia, myosteatosis, high visceral adipose tissue (VAT) and high visceral adipose tissue density (VATD). Using multivariable Cox proportional regression, we analyzed the association of clinical and transplant-related characteristics with overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM). In a multivariate regression model, patients with higher VATD had worse OS (HR 1.78; 95% confidence intervals CI 1.08-2.95, p = 0.02) and worse NRM (HR 2.31 95% CI 1.08-4.95, p = 0.02) than with lower VATD. Patients with lower levels of VAT also had worse RFS (HR 1.49 95% CI 1.03-2.15, p = 0.03). Sarcopenia and myosteatosis were not associated with outcomes. High pre-transplant VATD was associated with lower OS and higher NRM, and low pre-transplant VAT was associated with worse RFS in patients with NHL undergoing autologous HSCT.
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Transplantation de cellules souches hématopoïétiques , Lymphome malin non hodgkinien , Sarcopénie , Humains , Études rétrospectives , Sarcopénie/étiologie , Récidive tumorale locale , Lymphome malin non hodgkinien/thérapie , Lymphome malin non hodgkinien/anatomopathologie , Transplantation autologue , Composition corporelleRÉSUMÉ
INTRODUCTION: Heterotopic ossification (HO) is a known complication diagnosed following hip arthroscopy. PURPOSE/HYPOTHESIS: This study sought to review the current literature on chemoprophylaxis for HO following hip arthroscopy and to describe what agents and doses are being utilized. STUDY DESIGN: Systematic Review. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines on the use of chemoprophylactic medications for HO prevention following hip arthroscopy. Mechanical and radiation prophylaxis were not included in the current analysis. RESULTS: A total of 203 studies were identified, of which 15 were included with 6463 patients. There was one randomized control trial (RCT) and 4 additional comparative studies. The most commonly utilized chemoprophylactic agents were the following: naproxen (n â= â8), celecoxib (n â= â3), indomethacin (n â= â3), aspirin (n â= â1), etoricoxib (n â= â1), and etodolac (n â= â1), and non-specific non-steroidal anti-inflammatory drugs (NSAIDs) (n â= â1). Naproxen was either given at a dose of 500 âmg once or twice daily for 2-4 weeks. RCTs and additional comparative studies showed significant HO prevention using chemoprophylactic agents following hip arthroscopy. CONCLUSIONS: HO is a known and common complication following hip arthroscopy. The current systematic review found significant heterogeneity across the literature with respect to specific chemoprophylactic agents and their dosing regimens aimed to reduce the incidence and severity of HO following hip arthroscopy. Additionally, this review demonstrates that most studies that utilize chemoprophylaxis use NSAIDs with successful reduction in the incidence of HO. LEVEL OF EVIDENCE: Level IV Evidence.
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Naproxène , Ossification hétérotopique , Humains , Naproxène/usage thérapeutique , Arthroscopie/effets indésirables , Complications postopératoires/prévention et contrôle , Anti-inflammatoires non stéroïdiens/usage thérapeutique , Ossification hétérotopique/étiologie , Ossification hétérotopique/prévention et contrôle , Ossification hétérotopique/épidémiologie , Chimioprévention/effets indésirablesRÉSUMÉ
With improvement in survival after chronic lymphocytic leukemia (CLL) diagnosis, the real-world burden of second hematological malignancies (SHM) has not been comprehensively assessed in recent era. We analyzed risk, incidence, and outcomes of SHM in CLL patients between 2000 and 2019 using SEER database. CLL patients had greater risk for hematological malignancies than general population [SIR, standardized incidence ratio (95% CI):2.58 (2.46-2.70); p < 0.05]. The risk for subsequent lymphoma increased by 1.75 folds in 2015-2019 compared to 2000-2004. The duration, after CLL diagnosis, of maximum risk for SHM decreased as 60-119 months for time-period 2000-2004, 6-11 months for 2005-2009 to 2-5 months for 2010-2014 and 2015-2019. Incidence of SHM was 2.5% in CLL survivors (1736/70,346) with lymphoid SHM being more common than myeloid SHM, and DLBCL being the most common pathology (n = 610, 35% of all SHM). Male sex, age ≤65 years at CLL diagnosis, and chemotherapy treatment were associated with higher risk for SHM. The median gap between CLL and SHM diagnoses was 46 months. The median survival for de-novo-AML, t-MN, CML, and aggressive NHL was 63, 86, 95, and 96 months respectively. Although SHM remains rare, there is increased risk in recent era, likely due to improved survival in CLL patients, necessitating active surveillance strategies.
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Tumeurs hématologiques , Leucémie chronique lymphocytaire à cellules B , Leucémie aigüe myéloïde , Lymphome malin non hodgkinien , Humains , Mâle , Sujet âgé , Leucémie chronique lymphocytaire à cellules B/épidémiologie , Lymphome malin non hodgkinien/complications , Tumeurs hématologiques/thérapie , Tumeurs hématologiques/complications , SurvivantsRÉSUMÉ
Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis, and engraftment. Secondary end points included chronic GVHD (cGVHD), organ toxicity, infection, relapse, nonrelapse mortality (NRM), and overall survival (OS). Ninety-six pts were randomly assigned to full-MTX (N = 49) or mini-MTX (N = 47). The majority (86%) used bone marrow grafts. There was no significant difference in grade 2-4 aGVHD (28% mini-MTX/MMF vs 27% full-MTX; P = .41); however higher incidence of grade 3-4 aGVHD (13% vs 4%; P = .07) with mini-MTX/MMF. Pts receiving mini-MTX/MMF had lower grade 3 or 4 mucositis and faster engraftment. There were no differences in moderate-to-severe cGVHD at 1 year or infections. Pts receiving mini-MTX/MMF experienced less nephrotoxicity and respiratory failure. There was no difference in the 1-year relapse (19% vs 21%; P = .89) and OS (72% vs 71%; P = .08), and mini-MTX/MMF was associated with lower but nonsignificant NRM (11% vs 22%; P = .06). Compared with full-MTX, mini-MTX/MMF was associated with no difference in grade 2-4 aGVHD and a more favorable toxicity profile. The higher severe aGVHD warrants further study to optimize this regimen. The trial was registered at www.clinicaltrials.gov as #NCT01951885.
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Maladie du greffon contre l'hôte , Inflammation muqueuse , Humains , Tacrolimus/usage thérapeutique , Méthotrexate/usage thérapeutique , Inflammation muqueuse/étiologie , Inflammation muqueuse/prévention et contrôle , Récidive tumorale locale/traitement médicamenteux , Immunosuppresseurs/usage thérapeutique , Maladie du greffon contre l'hôte/étiologie , Maladie du greffon contre l'hôte/prévention et contrôle , Maladie du greffon contre l'hôte/traitement médicamenteux , Acide mycophénolique/usage thérapeutique , Antienzymes/usage thérapeutiqueRÉSUMÉ
Adaptive oscillators are a subset of nonlinear oscillators that can learn and encode information in dynamic states. By appending additional states onto a classical Hopf oscillator, a four-state adaptive oscillator is created that can learn both the frequency and amplitude of an external forcing frequency. Analog circuit implementations of nonlinear differential systems are usually achieved by using operational amplifier-based integrator networks, in which redesign procedures of the system topology is time consuming. Here, an analog implementation of a four-state adaptive oscillator is presented for the first time as a field-programmable analog array (FPAA) circuit. The FPAA diagram is described, and the hardware performance is presented. This simple FPAA-based oscillator can be used as an analog frequency analyzer, as its frequency state will evolve to match the external forcing frequency. Notably, this is done without any analog-to-digital conversion or pre-processing, making it an ideal frequency analyzer for low-power and low-memory applications.
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Lateral patellar dislocations often occur in a young, athletic population of recurrent dislocators with generalized laxity and an interest in returning to an active lifestyle. A recent appreciation for the distal patellotibial complex has directed surgeons toward attempting to re-create the native anatomy and knee biomechanics during medial patellar reconstructive procedures. By reconstructing the medial patellotibial ligament (MPTL) in addition to the medial patella-femoral ligament (MPFL) and medial quadriceps tendon-femoral ligament (MQTFL), the current article describes a potentially more stable construct that can be utilized in patients with subluxation with the knee in full extension, patellar instability with the knee in deep flexion, genu recurvatum, and generalized hyperlaxity. Additionally, the current technique utilizes a tibialis anterior allograft. The purpose of this Technical Note is to describe, in detail, the current authors' technique for a combined MPFL, MQTFL, and MPTL reconstruction.
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Symptomatic superior labral anterior and posterior (SLAP) tears have become an increasingly common diagnosis, particularly within the competitive overhead athlete population. Type II SLAP tears are the most encountered variant in overhead throwing athletes. Given the high incidence of false positives on advanced imaging, corroborating the history and physical examination with imaging is paramount to accurately establish a SLAP lesion diagnosis. Previous studies have reported conflicting success rates with conservative management, but the number of pitching athletes able to return to prior level of performance with nonsurgical management strategies has been unsatisfactory. Although there has historically been a notable disconnect between the incidence of SLAP tears in the literature and the number of SLAP repairs in recent investigations, high-grade or unstable tears may be candidates for débridement, labral repair, biceps tenodesis, or less frequently, biceps tenotomy. Biceps tenodesis has been increasingly used for the management of these lesions, with recent studies reporting high rates of return to sport, high satisfaction, and good to excellent patient-reported outcomes in carefully selected athletes.
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Lésions de l'épaule , Articulation glénohumérale , Ténodèse , Humains , Lésions de l'épaule/chirurgie , Articulation glénohumérale/chirurgie , Arthroscopie/méthodes , Muscles squelettiques/chirurgie , Ténodèse/méthodesRÉSUMÉ
INTRODUCTION: We assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for brain amyloid beta (Aß) pathology confirmation in the EMERGE and ENGAGE clinical trials. METHODS: EMERGE and ENGAGE were randomized, placebo-controlled, Phase 3 trials of aducanumab in participants with early Alzheimer's disease. Concordance between CSF biomarkers (Aß42, Aß40, phosphorylated tau 181, and total tau) and amyloid PET status (visual read) at screening was examined. RESULTS: Robust concordance between CSF biomarkers and amyloid PET visual status was observed (for Aß42/Aß40, AUC: 0.90; 95% CI: 0.83-0.97; p < 0.0001), confirming CSF biomarkers as a reliable alternative to amyloid PET in these studies. Compared with single CSF biomarkers, CSF biomarker ratios showed better agreement with amyloid PET visual reads, demonstrating high diagnostic accuracy. DISCUSSION: These analyses add to the growing body of evidence supporting CSF biomarkers as reliable alternatives to amyloid PET imaging for brain Aß pathology confirmation. HIGHLIGHTS: CSF biomarkers and amyloid PET concordance were assessed in Ph3 aducanumab trials. Robust concordance between CSF biomarkers and amyloid PET was observed. CSF biomarker ratios increased diagnostic accuracy over single CSF biomarkers. CSF Aß42/Aß40 demonstrated high concordance with amyloid PET. Results support CSF biomarker testing as a reliable alternative to amyloid PET.
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Maladie d'Alzheimer , Peptides bêta-amyloïdes , Humains , Peptides bêta-amyloïdes/liquide cérébrospinal , Maladie d'Alzheimer/imagerie diagnostique , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/liquide cérébrospinal , Protéines tau/liquide cérébrospinal , Tomographie par émission de positons , Amyloïde , Marqueurs biologiques/liquide cérébrospinal , Fragments peptidiques/liquide cérébrospinalRÉSUMÉ
BACKGROUND: Superior labrum anterior to posterior (SLAP) lesions are targeted on physical examination using a variety of provocative maneuvers. PURPOSE/HYPOTHESIS: The purpose was to conduct a systematic review on the performance of physical examination maneuvers in diagnosing SLAP lesions and to perform a meta-analysis comparing the sensitivity and specificity of these examinations both individually and in combination. The null hypothesis stated that there would be no significant difference in the sensitivity or specificity of the included physical examination tests, neither individually nor in combination. STUDY DESIGN: Meta-analysis and systematic review; Level of evidence, 4. METHODS: A systematic review was performed with the inclusion criteria of studies that reported either the sensitivities and specificities or the number of true-positive, true-negative, false-positive, or false-negative results for at least 1 maneuver for identifying SLAP lesions. A meta-analysis was performed to determine the sensitivity and specificity of individual maneuvers. Additional analysis determined the performance of these maneuvers when combined in series and parallel. In series, all must be present to be considered positive. In parallel, any single positive test forces the overall combination to be considered positive. Only tests that were included in ≥3 studies were considered in the meta-analysis and those included in ≥4 studies were considered in the combination analysis. RESULTS: Overall, 862 studies were identified, 18 of which were included in the systematic review and meta-analysis. The physical examinations included were the O'Brien (n = 16), speed (n = 8), Yergason (n = 6), anterior slide (n = 8), crank (n = 7), Jobe (n = 5), dynamic labral shear (n = 3), Kim 2 (n = 3), and biceps groove tenderness tests (n = 3). All combinations of 2 to 5 maneuvers in both series and parallel were considered. The O'Brien and crank test combination was the most sensitive 2-test combination in both parallel and series. The Yergason and anterior slide test combination was the most specific 2-test combination in parallel and series. CONCLUSION: This systematic review and meta-analysis reports an updated meta-analysis considering the sensitivity and specificity of common physical examination maneuvers used in the diagnosis of SLAP lesions and considers these values for tests in both series and parallel combinations. The present analysis demonstrates improved specificities when tests are considered in series and improved sensitivities when considered in parallel combination.
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Lésions de l'épaule , Articulation glénohumérale , Humains , Sensibilité et spécificité , Examen physique/méthodes , Épaule , ArthroscopieRÉSUMÉ
Busulfan-based conditioning regimens are associated with serious toxicities and literature reports increased risk of toxicities when daily area under the curve concentrations exceed 6000â µM-minute. We implemented real time pharmacokinetic-guided therapeutic drug monitoring of busulfan for myeloablative conditioning regimens. The objective was to compare toxicity of intravenous busulfan before and after therapeutic drug monitoring implementation. The primary endpoint was incidence of hepatotoxicity. Medical records were retrospectively reviewed with weight-based dose Busulfan/Cyclophosphamide (BuCy) conditioning from August 2017 through March 2018 (N = 14) and therapeutic drug monitoring from April 2018 through December 2018 (N = 22). Recipients of busulfan therapeutic drug monitoring were younger than those receiving weight-based dose (median: 45 vs. 58 years, p = 0.008). No other baseline differences were observed. There was no difference in hepatotoxicity between therapeutic drug monitoring and weight-based dose (median 1 vs. 0 days, p = 0.40). In the therapeutic drug monitoring group, 45% of patients had increases and 41% had decreases in busulfan dose after Bu1. Repeat pharmacokinetic after Bu2 were required in 32% of patients. A pharmacokinetic dose monitoring program for myeloablative conditioning intravenous busulfan regimens may be considered a safe practice in stem cell transplant recipients. The majority of patients receiving pharmacokinetic-guided therapeutic drug monitoring required dose changes and therapeutic drug monitoring patients had no significant difference in toxicity compared to those receiving weight-based dose.