Regenerative Anterior Cruciate Ligament Healing in Youth and Adolescent Athletes: The Emerging Age of Recovery Science.

Anterior cruciate ligament (ACL) injuries mainly arise from non-contact mechanisms during sport performance, with most injuries occurring among youth or adolescent-age athletes, particularly females. The growing popularity of elite-level sport training has increased the total volume, intensity and frequency of exercise and competition loading to levels that may exceed natural healing capacity. Growing evidence suggests that the prevailing mechanism that leads to non-contact ACL injury from sudden mechanical fatigue failure may be accumulated microtrauma. Given the consequences of primary ACL injury on the future health and quality of life of youth and adolescent athletes, the objective of this review is to identify key "recovery science" factors that can help prevent these injuries. Recovery science is any aspect of sports training (type, volume, intensity, frequency), nutrition, and sleep/rest or other therapeutic modalities that may prevent the accumulated microtrauma that precedes non-contact ACL injury from sudden mechanical fatigue failure. This review discusses ACL injury epidemiology, current surgical efficacy, the native ACL vascular network, regional ACL histological complexities such as the entheses and crimp patterns, extracellular matrix remodeling, the concept of causal histogenesis, exercise dosage and ligament metabolism, central nervous system reorganization post-ACL rupture, homeostasis regulation, nutrition, sleep and the autonomic nervous system. Based on this information, now may be a good time to re-think primary ACL injury prevention strategies with greater use of modified sport training, improved active recovery that includes well-planned nutrition, and healthy sleep patterns. The scientific rationale behind the efficacy of regenerative orthobiologics and concomitant therapies for primary ACL injury prevention in youth and adolescent athletes are also discussed.

Incidence of Instability Following Primary Total Hip Arthroplasty Continues to Decline in the Medicare Population.

BACKGROUND: Instability has been the primary cause of failure following primary total hip arthroplasty (THA) leading to revision hip surgery. The purpose of this study was to determine if instability rates have further declined following advances in primary THA, including dual mobility articulations, direct anterior approaches, advanced technologies, and improved knowledge of the hip-spine relationships. METHODS: Using the 5% Medicare Part B claims data from 1999 to 2019, we identified 81,573 patients who underwent primary THA for osteoarthritis. Patients who experienced instability at 3 months, 6 months, 1 year, and 2 years were identified. Multivariate cox regression analyses evaluated the effect of patient and procedure characteristics on the risk of instability. RESULTS: Instability at 1 year following primary THA declined from approximately 4% in 2000 to 2.3% in 2010 and 1.6% in 2018. The leading cause of revision surgery was infection (18.6%), followed by periprosthetic fracture (14%), mechanical loosening (11.5%), and instability (9.4%). High-risk groups for instability continue to include increased age, higher Charlson index, obesity, lumbar spine pathology, and neurocognitive disorders. CONCLUSION: Instability is no longer the leading etiology of failure following primary THA with a decline of approximately 40% over the past decade. Infection, periprosthetic fracture, mechanical loosening, and then instability are now the leading causes of failure. Multiple factors may play a role in the decline of instability, including increased use of dual mobility articulations, direct anterior approaches, improved knowledge of the hip-spine relationships, and use of advanced technologies.

Reamer Irrigator Aspirator Versus Iliac Crest Bone Grafting and Proximal Tibial Curettage: Is There a Difference in Blood Loss and Transfusion Rates?

OBJECTIVES: To compare blood loss and transfusion rates among reamer irrigator aspirator (RIA), iliac crest bone graft (ICBG), and proximal tibial curettage (PTC) for autograft harvest. DESIGN: Retrospective comparative study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: The study included 139 adult patients treated between 2011 and 2018. INTERVENTIONS: Nonunion repair of the femur or tibia using either RIA (n = 64), ICBG (n = 59), or PTC (n = 16) for autograft. MAIN OUTCOME MEASUREMENTS: Estimated blood loss and transfusion rates. RESULTS: Patient demographics, surgical indications, and medical comorbidities that affect bleeding did not differ among the groups. Estimated blood loss (mL) was significantly higher in the RIA group [RIA: 388 ± 368 (50-2000), ICBG: 286 ± 344 (10-2000), PTC: 196 mL ± 219 (10-700), P < 0.01]. The transfusion rate was also significantly higher in the RIA group (RIA 14%, ICBG 0%, PTC 0%, P < 0.01). The amount of graft obtained was higher in the RIA group (RIA = 48.3 mL, ICBG = 31.0 mL, PTC = 18.8 mL, P < 0.01), and the operative time (hours) was longer in the RIA group (RIA = 2.8, ICBG = 2.6, PTC = 1.9, P = 0.04). CONCLUSION: Estimated blood loss and transfusion rates were significantly higher in patients undergoing RIA compared with those in patients undergoing ICBG and PTC; however, the incidence of transfusion after RIA (14%) was considerably lower than previous reports. These findings suggest that the risk of transfusion after RIA is present and clinically significant but lower than previously believed, and it is likely affected by the amount of graft obtained and complexity of the nonunion repair. The risk of transfusion should be discussed with patients and the choice of RIA carefully evaluated in patients who have anemia or risk factors of bleeding. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases.

BACKGROUND: It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. OBJECTIVE: To characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission. DESIGN: Case report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. SETTING: Tertiary care center. PATIENTS: Two men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors. MEASUREMENTS: Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. RESULTS: No HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients. LIMITATION: The study involved only 2 patients. CONCLUSION: Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission. PRIMARY FUNDING SOURCE: Foundation for AIDS Research and National Institute of Allergy and Infectious Diseases.

Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.

The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however, the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK-cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1-positive and HIV-1-negative individuals were assessed (N = 42 and N = 40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3(+) NK cells. Further analysis showed that KIR2DL1(+) NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3(+) NK cells. KIR2DL1-3(+) NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes, as measured by degranulation and IFN-γ and TNF-α production. These results identify a novel relationship between HLA-C and KIR2DL(+) NK-cell subsets and demonstrate that HLA-C-mediated licensing modulates NK-cell responses to primary HIV-1 infection.

Tumor necrosis factor α is associated with viral control and early disease progression in patients with HIV type 1 infection.

Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease progression is not well characterized. Ninety patients with untreated primary HIV-1 infection were studied to determine associations of inflammatory proteins with early disease progression. High plasma tumor necrosis factor α (TNF-α) levels (≥8.5 pg/mL) were significantly associated with an increased viral load set point and shorter times to reaching a CD4(+) T-cell count of <500 cells/mm(3) and initiating antiretroviral therapy. The increased risk of reaching a CD4(+) T-cell count of <500 cells/mm(3) in the group with high TNF-α levels was driven by viral load but was independent of concurrent CD4(+) T-cell count. Thus, TNF-α appears to be an important mediator of inflammation in patients with poor viral control and early HIV-1 disease progression.