Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials.

OBJECTIVES: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF. METHODS: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks. RESULTS: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment-emergent resistance. Drug-related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate-containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01). CONCLUSIONS: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment-emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107).

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age.

OBJECTIVES: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study. METHODS: In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96. RESULTS: Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0-98.1) and 74.4% (64/86; 95% CI 63.9-83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR -2.3, 2.0). Median self-reported adherence was 100% (IQR 100-100%). CONCLUSIONS: Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population.

Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Virologically Suppressed Adults With Human Immunodeficiency Virus.

BACKGROUND: Bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) is guideline-recommended treatment for human immunodeficiency virus type 1 (HIV-1). We evaluated whether people receiving dolutegravir (DTG) plus F/TAF or F/TDF (tenofovir disoproxil fumarate) with viral suppression can switch to B/F/TAF without compromising safety or efficacy, regardless of preexisting nucleoside reverse transcriptase inhibitor (NRTI) resistance. METHODS: In this multicenter, randomized, double-blinded, active-controlled, noninferiority trial, we enrolled adults who were virologically suppressed for ≥6 months before screening (with documented/suspected NRTI resistance) or ≥3 months before screening (with no documented/suspected NRTI resistance) on DTG plus either F/TDF or F/TAF. We randomly assigned (1:1) participants to switch to B/F/TAF or DTG + F/TAF once daily for 48 weeks, each with matching placebo. The primary endpoint was proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at week 48 (snapshot algorithm); the prespecified noninferiority margin was 4%. RESULTS: Five hundred sixty-seven adults were randomized; 565 were treated (284 B/F/TAF, 281 DTG + F/TAF). At week 48, B/F/TAF was noninferior to DTG + F/TAF, as 0.4% (1/284) vs 1.1% (3/281) had HIV-1 RNA ≥50 copies/mL (difference, -0.7% [95.001% confidence interval {CI}, -2.8% to 1.0%]). There were no significant differences in efficacy among participants with suspected or confirmed prior NRTI resistance (n = 138). No participant had treatment-emergent drug resistance. Median weight change from baseline at week 48 was +1.3 kg (B/F/TAF) vs +1.1 kg (DTG + F/TAF) (P = .46). Weight change differed by baseline NRTIs (+2.2 kg [F/TDF] and +0.6 kg [F/TAF], P < .001), with no differences between B/F/TAF and DTG + F/TAF. CONCLUSIONS: The single-tablet regimen B/F/TAF is a safe, effective option for people virologically suppressed on DTG plus either F/TDF or F/TAF, including in individuals with preexisting resistance to NRTIs. CLINICAL TRIALS REGISTRATION: NCT03110380.

Weight Change Following Antiretroviral Therapy Switch in People With Viral Suppression: Pooled Data from Randomized Clinical Trials.

BACKGROUND: We sought to identify factors associated with weight gain in randomized clinical trials of antiretroviral therapy (ART) switch. METHODS: We explored the effects of demographic factors, clinical characteristics, and ART on weight gain in a pooled analysis of 12 prospective clinical trials, wherein virologically suppressed people living with human immunodeficiency virus (PWH) were randomized to switch or remain on a stable baseline regimen (SBR). RESULTS: Both PWH randomized to switch ART (n = 4166) and those remaining on SBR (n = 3150) gained weight. Median weight gain was greater in those who switched (1.6 kg, interquartile range [IQR], -.05 to 4.0 vs 0.4 kg, [IQR], -1.8 to 2.4 at 48 weeks, P < .0001), with most weight gain occurring in the first 24 weeks after switch. Among baseline demographic and clinical characteristics, only younger age and lower baseline body mass index were associated with any or ≥10% weight gain. By week 48, 4.6% gained ≥10% weight (6.4% of switch and 2.2% of SBR), the greatest risk was with switch from efavirenz (EFV) to rilpivirine (RPV) or elvitegravir/cobicistat and switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Switch from abacavir to TAF was associated with less weight gain than switch from TDF to TAF and was not associated with increased risk for ≥10% weight gain. CONCLUSIONS: Moderate weight gain after ART switch was common and usually plateaued by 48 weeks. Baseline ART was a predictor of post-switch weight gain; participants who switched off of EFV and TDF had the greatest weight gain. The biological mechanisms that underlie the differential effects of switching ART agents on weight and associated clinical implications require further study.

Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants.

OBJECTIVES: Two Phase 3, randomized, double-blind, active-controlled studies of initial HIV-1 treatment demonstrated that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was non-inferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC; Study 1489) or to DTG+F/TAF (Study 1490) through 144 weeks. In both studies, there was no emergent resistance to study drugs. Here, the 3 year resistance analysis and impact of baseline resistance substitutions on treatment response are described. METHODS: Population sequencing of HIV-1 protease and reverse transcriptase (RT) was performed at screening. Retrospective baseline next generation sequencing of protease, RT and integrase (IN) was analysed at a ≥ 15% cutoff. Resistance analyses were performed on participants with confirmed viral rebound of HIV-1 RNA ≥200 copies/mL through Week 144 or last visit who did not resuppress to <50 copies/mL while on study drug. RESULTS: Transmitted primary drug resistance substitutions were present in the following proportions of participants: integrase strand transfer inhibitor (INSTI) resistance (-R) in 1.3% (17/1270) of participants; NRTI-R in 2.7% (35/1274); NNRTI-R in 14.1% (179/1274); and PI-R in 3.5% (44/1274). These pre-existing resistance substitutions not associated with study drug did not affect treatment outcomes. One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144. In total, 21 participants qualified for resistance testing [1.3% (8/634) B/F/TAF; 1.9% (6/315) DTG/ABC/3TC; 2.2% (7/325) DTG+F/TAF]; none had emergent resistance to study drugs. CONCLUSIONS: Treatment with B/F/TAF, DTG/ABC/3TC, or DTG+F/TAF achieved high, durable rates of virological suppression in HIV-1 treatment-naive participants. The presence of pre-existing resistance substitutions did not affect treatment outcomes, and there was no treatment-emergent resistance.

Low Back Pain Improves After Surgery for Lesser Trochanteric-Ischial Impingement.

PURPOSE: To assess the effects of surgery for lesser trochanteric-ischial impingement (LTI) on low back pain. METHODS: The records of patients with LTI who underwent endoscopic partial resection of the lesser trochanter (LT) between May of 2017 and February of 2019 were reviewed. Inclusion criteria were the presence of low back pain in association with hip pain, diagnosis of LTI, and partial resection of the LT to treat LTI. Exclusion criteria were less than 12 months of postoperative follow-up and hip or spine surgery after the LTI surgery. Patients were assessed before surgery and at the most recent follow-up with the modified Harris Hip Score and Oswestry Disability Index for lumbar spine. RESULTS: Thirty patients (31 hips) met the inclusion criteria. Four patients were lost to follow-up. Two patients with borderline dysplasia and grade 1 and 2 osteoarthritis underwent total hip arthroplasty after the partial resection of the LT. The results are presented considering the remaining 24 patients (25 hips). The average age at surgery was 51 years (range 32-65 years). The mean follow-up after the surgery for LTI was 19 months (range 12-35 months). The mean ± SD ODI improved from 48% ± 15 before the LTI surgery to 21% ± 22 (P < .001) at the most recent follow-up. Improvement in the Oswestry Disability Index above the minimal clinical important difference was observed in 16 patients (67%) following the LTI surgery. The mean ± SD modified Harris Hip Score improved from 55.8 ± 14 before LTI surgery to 81.3 ± 14.3 (P < .001). CONCLUSIONS: Decrease in low back pain above the minimal clinically important difference is observed in 2 of 3 patients after partial resection of the LT. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Femoral Derotation Osteotomy Improves Hip and Spine Function in Patients With Increased or Decreased Femoral Torsion.

PURPOSE: To evaluate the outcomes of proximal femoral derotation osteotomy (PFDO) on the hip and spine function of patients with abnormal femoral torsion. METHODS: This retrospective study included patients who underwent PFDO to treat increased or decreased femoral torsion between July 2014 and February 2019. The exclusion criteria were: previous fracture, fixation of slipped capital femoral epiphysis or osteotomy in the ipsilateral femur; PFDO associated to varus or valgus osteotomy; Tönnis grade 2 or 3 osteoarthritis; and PFDO performed to treat knee abnormalities. Hip function was assessed through the modified Harris Hip Score (mHHS). A subgroup of consecutive patients with low back pain before the PFDO and operated after 2017 had the spine function assessed through the Oswestry disability index (ODI). RESULTS: A total of 37 hips (34 patients) were studied: 15 hips with increased femoral torsion and 22 with decreased femoral torsion. Eight patients were male and 26 were female. The average age at PFDO was 33 years (range, 15-54 years). At a mean follow-up of 24 months (range, 12-65 months), the mean mHHS improved from 58.1 ± 14.3 before PFDO to 82 ± 15.6 at the most recent follow-up (P < .001). Improvement in the mHHS above the minimum clinically important difference (MCID) was observed in 33 hips (89%). In the subgroup of 14 consecutive patients with ODI available, the ODI improved from a mean of 45% ± 16% before the PFDO to 22% ± 17% at the most recent follow-up (P = .001). Nine (64.3%) of the 14 patients presented improvement in the ODI above the MCID. Revision procedure with a larger intramedullary nail was necessary in 2 hips to treat nonunion. CONCLUSION: Proximal femoral derotation osteotomy improves the hip and spine function in patients with increased or decreased femoral torsion and nonarthritic hips. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Deep gluteal syndrome is defined as a non-discogenic sciatic nerve disorder with entrapment in the deep gluteal space: a systematic review.

PURPOSE: Clinicians are not confident in diagnosing deep gluteal syndrome (DGS) because of the ambiguity of the DGS disease definition and DGS diagnostic pathway. The purpose of this systematic review was to identify the DGS disease definition, and also to define a general DGS diagnostic pathway. METHODS: A systematic search was performed using four electronic databases: PubMed, MEDLINE, EMBASE, and Google Scholar. In eligibility criteria, studies in which cases were explicitly diagnosed with DGS were included, whereas review articles and commentary papers were excluded. Data are presented descriptively. RESULTS: The initial literature search yielded 359 articles, of which 14 studies met the eligibility criteria, pooling 853 patients with clinically diagnosed with DGS. In this review, it was discovered that the DGS disease definition was composed of three parts: (1) non-discogenic, (2) sciatic nerve disorder, and (3) nerve entrapment in the deep gluteal space. In the diagnosis of DGS, we found five diagnostic procedures: (1) history taking, (2) physical examination, (3) imaging tests, (4) response-to-injection, and (5) nerve-specific tests (electromyography). History taking (e.g. posterior hip pain, radicular pain, and difficulty sitting for 30 min), physical examination (e.g. tenderness in deep gluteal space, pertinent positive results with seated piriformis test, and positive Pace sign), and imaging tests (e.g. pelvic radiographs, spine and pelvic magnetic resonance imaging (MRI)) were generally performed in cases clinically diagnosed with DGS. CONCLUSION: Existing literature suggests the DGS disease definition as being a non-discogenic sciatic nerve disorder with entrapment in the deep gluteal space. Also, the general diagnostic pathway for DGS was composed of history taking (posterior hip pain, radicular pain, and difficulty sitting for 30 min), physical examination (tenderness in deep gluteal space, positive seated piriformis test, and positive Pace sign), and imaging tests (pelvic radiographs, pelvic MRI, and spine MRI). This review helps clinicians diagnose DGS with more confidence. LEVEL OF EVIDENCE: IV.

Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks.

In clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3% integrase strand transfer inhibitor resistance (INSTI-R), 2.7% nucleoside reverse transcriptase inhibitor resistance (NRTI-R), 14.1% nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R), and 3.5% protease inhibitor resistance (PI-R) in the 1,274 participants from these studies. These mutations did not affect treatment outcomes. Resistance analyses in 13 virologic failures found no emergent resistance to study drugs.

Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.

OBJECTIVES: Studies 1878 and 1844 demonstrated non-inferior efficacy of switching suppressed HIV-1-infected adults to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus continuing boosted PI-based triple regimens or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Here, detailed analyses of pre-existing resistance in the two BIC/FTC/TAF switch studies and efficacy at week 48 are described. METHODS: Pre-existing resistance was assessed from historical genotypes (documented resistance to study drugs was excluded) and by retrospective baseline proviral archive DNA genotyping from whole blood. Outcomes were based on HIV-1 RNA at week 48 with missing values imputed using the last on-treatment observation carried forward method. RESULTS: Cumulative pre-existing resistance data from historical and proviral genotypes were obtained for 95% (543/570) of participants who switched to BIC/FTC/TAF. Altogether, 40% (217/543) had one or more pre-existing primary resistance substitutions in protease, reverse transcriptase and/or integrase. Pre-switch NRTI resistance was detected in 16% (89/543) of BIC/FTC/TAF-treated participants, with M184V or M184I detected by proviral genotyping in 10% (54/543). At week 48, 98% (561/570) of all BIC/FTC/TAF-treated participants versus 98% (213/217) with pre-existing resistance and 96% (52/54) with archived M184V/I had HIV-1 RNA <50 copies/mL. No BIC/FTC/TAF-treated participants developed treatment-emergent resistance to study drugs. CONCLUSIONS: Pre-existing resistance substitutions, notably M184V/I, were unexpectedly common among suppressed participants who switched to BIC/FTC/TAF. High rates of virological suppression were maintained in the overall study population and in those with pre-existing resistance, including M184V/I, for up to 48 weeks of BIC/FTC/TAF treatment with no resistance development. These results indicate that BIC/FTC/TAF is an effective treatment option for suppressed patients, including those with evidence of archived NRTI resistance.

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug-drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine. METHODS: We did this double-blind, multicentre, active-controlled, randomised controlled non-inferiority trial at 122 outpatient centres in nine countries in Europe, Latin America, and North America. We enrolled HIV-1 infected adults (aged ≥18 years) who were previously untreated (HIV-1 RNA ≥500 copies per mL); HLA-B*5701-negative; had no hepatitis B virus infection; screening genotypes showing sensitivity to emtricitabine, tenofovir, lamivudine, and abacavir; and an estimated glomerular filtration rate of 50 mL/min or more. Participants were randomly assigned (1:1), via a computer-generated allocation sequence (block size of four), to receive coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg, with matching placebo, once daily for 144 weeks. Randomisation was stratified by HIV-1 RNA (≤100 000 copies per mL, >100 000 to ≤400 000 copies per mL, or >400 000 copies per mL), CD4 count (<50 cells per µL, 50-199 cells per µL, or ≥200 cells per µL), and region (USA or ex-USA). Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to group assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 48, as defined by the US Food and Drug Administration snapshot algorithm, with a prespecified non-inferiority margin of -12%. All participants who received one dose of study drug were included in primary efficacy and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02607930. FINDINGS: Between Nov 13, 2015, and July 14, 2016, we randomly assigned 631 participants to receive coformulated bictegravir, emtricitabine, and tenofovir alafenamide (n=316) or coformulated dolutegravir, abacavir, and lamivudine (n=315), of whom 314 and 315 patients, respectively, received at least one dose of study drug. At week 48, HIV-1 RNA less than 50 copies per mL was achieved in 92·4% of patients (n=290 of 314) in the bictegravir, emtricitabine, and tenofovir alafenamide group and 93·0% of patients (n=293 of 315) in the dolutegravir, abacavir, and lamivudine group (difference -0·6%, 95·002% CI -4·8 to 3·6; p=0·78), demonstrating non-inferiority of bictegravir, emtricitabine, and tenofovir alafenamide to dolutegravir, abacavir, and lamivudine. No individual developed treatment-emergent resistance to any study drug. Incidence and severity of adverse events was mostly similar between groups except for nausea, which occurred less frequently in patients given bictegravir, emtricitabine, and tenofovir alafenamide than in those given dolutegravir, abacavir, and lamivudine (10% [n=32] vs 23% [n=72]; p<0·0001). Adverse events related to study drug were less common with bictegravir, emtricitabine, and tenofovir alafenamide than with dolutegravir, abacavir, and lamivudine (26% [n=82] vs 40% [n=127]), the difference being driven by a higher incidence of drug-related nausea in the dolutegravir, abacavir, and lamivudine group (5% [n=17] vs 17% [n=55]; p<0·0001). INTERPRETATION: At 48 weeks, coformulated bictegravir, emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent resistance. Bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine. Because coformulated bictegravir, emtricitabine, and tenofovir alafenamide does not require HLA B*5701 testing and provides guideline-recommended treatment for individuals co-infected with HIV and hepatitis B, this regimen might lend itself to rapid or same-day initiation of therapy in the clinical setting. FUNDING: Gilead Sciences.

Editorial Commentary: Hip Labral Revision Reconstruction in a Fellowship Training Center: A Report From the Mountains.

Hip labral reconstruction has proven to be a successful technique in restoring normal labrum function. However, sometimes revision surgery is required. A recent, well-designed prospective study provides significant support for revision labral reconstruction, showing how it leads to improved hip mechanics and reduction in pain. The success of the study design and this report is a testament to an educational institution dedicated to fellowship training.

Accuracy of 3 Clinical Tests to Diagnose Proximal Hamstrings Tears With and Without Sciatic Nerve Involvement in Patients With Posterior Hip Pain.

PURPOSE: To determine the diagnostic accuracy of the active hamstring test at 30° (A-30) and 90° (A-90) of knee flexion, the long stride heel strike (LSHS) test, and combination of the 3 tests for individuals with hamstring tendon tears, with and without sciatic nerve involvement. METHODS: A retrospective review of 564 consecutive clinical records identified 42 subjects with a mean age of 50.31 ± 15 years who underwent a standard physical examination prior to magnetic resonance imaging (MRI) evaluation and diagnostic injection for posterior hip. The physical examination included the A-30, A-90, and LSHS tests. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated to determine the diagnostic accuracy of these 3 tests. RESULTS: Forty-two subjects (female = 32 and male = 10) with a mean age of 50.31 years (range 15-77, ± SD 14.52) met the inclusion criteria and were included in the review. Based on MRI and/or injection, 64.28% (27/42) of subjects were diagnosed with hamstring tear. Fourteen (51.85%) presented with sciatic nerve involvement. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test were as follows: A-30 knee flexion: 0.73, 0.97, 23.43, 0.28, and 84.73; A-90 knee flexion: 0.62, 0.97, 20.00, 0.39, and 51.67; LSHS: 0.55, 0.73, 2.08, 0.61, and 3.44. The most accurate findings were obtained when the results of the A-30 and A-90 were combined, with sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of 0.84, 0.97, 26.86, 0.17, and 161.89, respectively. CONCLUSION: The combination of the active hamstring A-30 and A-90 tests proved to be a highly accurate and valuable tool to diagnose proximal hamstring tendons tears with or without sciatic nerve involvement in subjects presenting with posterior hip pain. LEVEL OF EVIDENCE: Level III, diagnostic study.

Incorporating Hip Arthroscopy Into A Practice.

Hip arthroscopy is one of the most rapidly growing areas in orthopaedic surgery because of increased awareness of nonarthritic hip pathologies, advanced imaging modalities, and advanced techniques to reproducibly manage nonarthritic hip pathologies within a deep soft-tissue envelope and a constrained joint. In addition, more academic medical centers are providing residents with education on hip arthroscopy, and many hip preservation fellowships and courses are helping increase awareness of nonarthritic hip pathologies. Nonarthritic hip pathologies currently managed via hip arthroscopy include nonrepairable labral lesions, femoroacetabular impingement, hip instability, and hip fractures. Periarticular hip pathologies currently managed via endoscopy include greater trochanteric pain syndrome, tendinopathy and tears of the gluteus medius and minimus, partial and complete hamstring avulsions, and sciatic nerve entrapment. Ischiofemoral impingement may be addressed endoscopically via the deep gluteal space. Orthopaedic surgeons should understand the role and safety of hip arthroscopy in the pediatric population, specifically in the management of slipped capital femoral epiphysis, Legg-Calvé-Perthes disease, and septic arthritis of the hip. The efficacy of hip arthroscopy is limited, and hip arthroscopy is relatively contraindicated in patients with osteoarthritis and hip dysplasia. Complications can occur and likely are underreported in patients who undergo hip arthroscopy. Orthopaedic surgeons should understand practical issues associated with incorporating hip arthroscopy into a practice, including the difficult learning curve associated with hip arthroscopy and the reluctance of some payors to reimburse procedures performed arthroscopically because hip arthroscopy is a relatively new technology.

Editorial Commentary: Pioneering the Gluteal Interval: Understanding and Treating Undersurface and Full-Thickness Gluteus Medius Tears of the Hip.

Lateral-based hip disease is severely impairing for many patients. Treatment decision making requires a thorough understanding of the biomechanical and clinical interpretation of the physical examination. The outcomes of these under-recognized pathologies are explained with success. A recent study has described the diagnostic and surgical treatment outcomes of this impairing condition of partial and full-thickness gluteus medius tears.

Surgical Management of Deep Gluteal Syndrome Causing Sciatic Nerve Entrapment: A Systematic Review.

PURPOSE: To assess the causes, surgical indications, patient-reported clinical outcomes, and complications in patients with deep gluteal syndrome causing sciatic nerve entrapment. METHODS: Three databases (PubMed, Ovid [MEDLINE], and Embase) were searched by 2 reviewers independently from database inception until September 7, 2016. The inclusion criteria were studies reporting on both arthroscopic and open surgery and those with Level I to IV evidence. Systematic reviews, conference abstracts, book chapters, and technical reports with no outcome data were excluded. The methodologic quality of the studies was assessed with the MINORS (Methodological Index for Non-randomized Studies) tool. RESULTS: The search identified 1,539 studies, of which 28 (481 patients; mean age, 48 years) were included for assessment. Of the studies, 24 were graded as Level IV, 3 as Level III, and 1 as Level II. The most commonly identified causes were iatrogenic (30%), piriformis syndrome (26%), trauma (15%), and non-piriformis (hamstring, obturator internus) muscle pathology (14%). The decision to pursue surgical management was made based on clinical findings and diagnostic investigations alone in 50% of studies, whereas surgical release was attempted only after failed conservative management in the other 50%. Outcomes were positive, with an improvement in pain at final follow-up (mean, 23 months) reported in all 28 studies. The incidence of complications from these procedures was low: Fewer than 1% and 8% of open surgical procedures and 0% and fewer than 1% of endoscopic procedures resulted in major (deep wound infection) and minor complications, respectively. CONCLUSIONS: Although most of the studies identified were case series and reports, the results consistently showed improvement in pain and a low incidence of complications, particularly for endoscopic procedures. These findings lend credence to surgical management as a viable option for buttock pain caused by deep gluteal syndrome and warrant further investigation. LEVEL OF EVIDENCE: Level IV, systematic review of Level II through IV studies.

The Hip-Spine Effect: A Biomechanical Study of Ischiofemoral Impingement Effect on Lumbar Facet Joints.

PURPOSE: To assess the relation between ischiofemoral impingement (IFI) and lumbar facet joint load during hip extension in cadavers. METHODS: Twelve hips in 6 fresh T1-to-toes cadaveric specimens were tested. A complete pretesting imaging evaluation was performed using computed tomography scan. Cadavers were positioned in lateral decubitus and fixed to a dissection table. Both legs were placed on a frame in a simulated walking position. Through a posterior lumbar spine approach L3-4 and L4-5 facet joints were dissected bilaterally. In addition, through a posterolateral approach to the hip, the space between the ischium and the lesser trochanter was dissected and measured. Ultrasensitive, and previously validated, piezoresistive force sensors were placed in lumbar facet joints of L3-4 and L4-5. Lumbar facet loads during hip extension were measured in native hip conditions and after simulating IFI by performing lesser trochanter osteotomy and lengthening. Four paired t-tests were performed comparing normal and simulated IFI on the L3-L4 and L4-L5 facet joint loads. RESULTS: After simulating IFI, mean absolute differences of facet joint load were 10.8 N (standard error of the mean [SEM] ±4.53, P = .036) for L3-4 at 10° of hip extension, 13.71 N (SEM ±4.53, P = .012) for L3-4 at 20° of hip extension, 11.49 N (SEM ±4.33, P = .024) for L4-5 at 10° of hip extension, and 6.67 N (SEM ±5.43, P = .245) for L4-5 at 20° of hip extension. A statistically significant increase in L3-4 and L4-5 lumbar facet joint loads of 30.81% was found in the IFI state as compared with the native state during terminal hip extension. CONCLUSIONS: Limited terminal hip extension due to simulated IFI significantly increases L3-4 and L4-5 lumbar facet joint load when compared with non-IFI native hips. CLINICAL RELEVANCE: This biomechanical study directly links IFI to increased lumbar facet loads and supports the clinical findings of IFI causing lumbar pathology. Assessing and treating (open or endoscopic) hip disorders that limit extension could have benefit in patients with concomitant lower back symptoms.

Contribution of the Pubofemoral Ligament to Hip Stability: A Biomechanical Study.

PURPOSE: To determine the isolated function of the pubofemoral ligament of the hip capsule and its contribution to hip stability in external/internal rotational motion during flexion greater than 30° and abduction. METHODS: Thirteen hips from 7 fresh-frozen pelvis-to-toe cadavers were skeletonized from the lumbar spine to the distal femur with the capsular ligaments intact. Computed tomographic imaging was performed to ensure no occult pathological state existed, and assess bony anatomy. Specimens were placed on a surgical table in supine position with lower extremities resting on a custom-designed polyvinylchloride frame. Hip internal and external rotation was measured with the hip placed into a combination of the following motions: 30°, 60°, 110° hip flexion and 0°, 20°, 40° abduction. Testing positions were randomized. The pubofemoral ligament was released and measurements were repeated, followed by releasing the ligamentum teres. RESULTS: Analysis of the 2,106 measurements recorded demonstrates the pubofemoral ligament as a main controller of hip internal rotation during hip flexion beyond 30° and abduction. Hip internal rotation was increased up to 438.9% (P < .001) when the pubofemoral ligament was released and 412.9% (P < .001) when both the pubofemoral and teres ligament were released, compared with the native state. CONCLUSIONS: The hypothesis of the pubofemoral ligament as one of the contributing factors of anterior inferior hip stability by controlling external rotation of the hip in flexion beyond 30° and abduction was disproved. The pubofemoral ligament maintains a key function in limiting internal rotation in the position of increasing hip flexion beyond 30° and abduction. This cadaveric study concludes previous attempts at understanding the anatomical and biomechanical function of the capsular ligaments and their role in hip stability. CLINICAL RELEVANCE: The present study contributes to the understanding of hip stability and biomechanical function of the pubofemoral ligament.

Preemptive Analgesia in Hip Arthroscopy: A Randomized Controlled Trial of Preemptive Periacetabular or Intra-articular Bupivacaine in Addition to Postoperative Intra-articular Bupivacaine.

PURPOSE: To evaluate and compare the efficacy of intra-articular and periacetabular blocks for postoperative pain control after hip arthroscopy. METHODS: Forty-two consecutive patients scheduled for hip arthroscopy were randomized into 2 postoperative pain control groups. One group received preemptive intra-articular 20 mL of bupivacaine 0.5% injection, and the second group received preemptive periacetabular 20 mL of bupivacaine 0.5% injection. Before closure all patients received an additional dose of 20 mL of bupivacaine 0.5% intra-articularly. Data were compared with respect to postoperative pain with visual analog scale (VAS) and analgesic consumption, documented in a pain diary for 2 weeks after surgery. RESULTS: Twenty-one patients were treated with intra-articular injection, and 21 patients with peri-acetabular injection. There were no significant differences with regards to patient demographics or surgical procedures. VAS scores recorded during the first 30 minutes postoperatively and 18 hours after surgery were significantly lower in the periacetabular group compared with in the intra-articular group (0.667 ± 1.49 vs 2.11 ± 2.29; P < .045 and 2.62 ± 2.2 vs 4.79 ± 2.6; P < .009). There were no differences between the groups with regard to analgesic consumption. CONCLUSIONS: Periacetabular injection of bupivacaine 0.5% was superior to intra-articular injection in pain reduction after hip arthroscopy at 30 minutes and 18 hours postoperatively. However, total analgesic consumption over the first 2 postoperative weeks and VAS pain measurements were not significantly affected. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Influence of Aging on Microvascular Supply of the Gluteus Medius Tendon: A Cadaveric and Histologic Study.

PURPOSE: The purpose of this cadaveric study was to assess the relation between age and microvascular supply of 3 areas of the gluteus medius tendon using a previously validated CD31 immunohistochemistry staining technique. METHODS: Twenty-four fresh-frozen gluteus medius specimens were obtained through a posterolateral approach to the hip. Specimens aged 18 years or older, of either sex, and of any race were considered for this study. The average age of donors was 47.3 years (range, 18-68 years). Each sample was divided into 3 portions: musculotendinous, tendinous, and tendon-bone junction. H&E staining was used for qualitative structural analysis, and then all samples underwent staining with CD31 immunohistochemistry for quantitative assessment of vessels per square millimeter. A comparison of the microvessel density between zones according to age was performed by an analysis of variance. To evaluate the relation between microvessel supply and age, a regression model with curvilinear estimation was used. The data were fitted to a quadratic model. RESULTS: Vascular supply in transversal and longitudinal cuts regardless of the zone was, on average, 53.9 ± 32.1 vessels/mm2 and 51.1 ± 19.3 vessels/mm2, respectively. All the areas of the tendon showed a strength of relation (R) ranging from 0.41 to 0.76 between age and vascular supply. In addition, the proportion of vascular supply change explained by age (R2) was significant in most cases (ranging from 0.17 to 0.56, with P < .05). CONCLUSIONS: There is a chronological relation between aging and microvascular supply of the gluteus medius tendon, in which an initial increase occurs from 18 years of age to 30 to 40 years of age, with a progressive decrease after 50 years of age. CLINICAL RELEVANCE: The findings of our study may have implications for increased vulnerability of the gluteus medius tendon and decreased healing potential.