Associations of inflammatory and metabolic biomarkers with incident erosive hand osteoarthritis in the osteoarthritis initiative cohort.

OBJECTIVE: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes. METHOD: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status. RESULTS: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01). CONCLUSION: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression.

Liposomal Bupivacaine and Ropivacaine Adductor Canal Blocks for Anterior Cruciate Ligament Reconstruction Provide Similar Postoperative Analgesia.

The purpose of this study was to compare postoperative pain following anterior cruciate ligament (ACL) reconstruction (ACLR) in patients receiving an adductor canal block (ACB) with ropivacaine (R-ACB) or liposomal bupivacaine (LB-ACB). The secondary purpose was to compare opioid consumption. A prospective cohort study of patients undergoing ACLR at an academic medical center was conducted from November 1, 2018 to November 21, 2019. The first cohort received R-ACB and 30 tablets of 5/325 mg oxycodone/acetaminophen. After June 13, 2019, the second cohort received LB-ACB and 20 tablets of 5/325 mg oxycodone/acetaminophen with the reduction in opioids prescribed resulting from a hospital quality improvement initiative to decrease narcotic consumption. From postoperative days 0 through 6, pain was assessed thrice daily using a numeric rating scale. Total postoperative opioid consumption was reported via tablet count and converted to oral morphine equivalents (OMEs). During this period, 165 subjects underwent ACLR, and 126 met the eligibility criteria (44.4% female, 55.6% male; mean ± standard deviation: 28.7 ± 13.7 years). Sixty-six (52.4%) received LB-ACB, and 60 (47.6%) received R-ACB (p = 0.53). The most common graft utilized was quadriceps autograft (63.6% LB-ACB; 58.3% R-ACB, p = 0.76). Mean postoperative pain scores were similar between groups during the entire postoperative period (p ≥ 0.08 for POD 0-6). While postoperative opioid consumption was lower among patients receiving LB-ACB (median OME [interquartile range]: 28.6 [7.5-63.8] vs. 45.0 [15.0-75.0], p = 0.023), this only amounted to an average of 2.2 tablets. Patients receiving LB-ACB in the setting of ACLR reported similar postoperative pain compared with those receiving R-ACB. Despite the second aim of our study, we cannot make conclusions about the effect of each block on opioid consumption given that each cohort received different numbers of opioid tablets due to institutional pressure to reduce opioid prescribing. As few patients completed their opioid prescriptions or requested refills, further reduction in prescription size is warranted. Future studies are necessary to further elucidate the effect of LB-ACB versus R-ACB on postoperative pain and opioid consumption after ACLR.

Revision Anterior Cruciate Ligament Reconstruction with the All-Soft Tissue Quadriceps Tendon Autograft Has Acceptable Early and Intermediate-Term Outcomes.

PURPOSE: The purposes were to (1) examine early to intermediate-term clinical outcomes and complications of revision anterior cruciate ligament reconstruction (ACLR) using all-soft tissue quadriceps tendon (QT) autografts, and (2) compare quadriceps strength between patients who had hamstring versus patella tendon autografts in their previous reconstruction. METHODS: One hundred patients (52 males/48 females; 22.6 ± 8.0 years) undergoing revision ACLR with all-soft tissue QT autografts were prospectively followed. All revision procedures were performed by a single surgeon, using a minimally invasive graft harvest technique and suspensory fixation. Subjective assessment of knee function was obtained before and after surgery with the International Knee Documentation Committee (IKDC) survey. Postoperative knee laxity and isokinetic quadriceps strength were collected at regular intervals. Strength was reported as limb symmetry index (LSI; surgical side divided by nonsurgical side). Complications including hematomas, postoperative loss of knee extension, and graft failures were recorded. To determine clinical significance (P ≤ .05), outcomes were compared using analysis of variance or paired samples t-tests. RESULTS: The mean IKDC scores significantly improved (54.3 ± 13.0 vs 82.8 ± 13.8), with an average follow-up of 42.2 ± 21.2 months. There were no significant changes in knee laxity side-to-side differences: 6 weeks (1.2 ± 1.5 mm), 3 months (1.2 ± 1.8 mm), 6 months (1.4 ± 1.6 mm). Quadriceps LSIs significantly improved from 71.6% ± 19.3% at 6 months to 81.5% ± 19.3% at 12 months for 60°/s isokinetic testing and 76.6% ± 16.4% at 6 months to 83.9% ± 16.9% at 12 months for 180°/s testing. Graft harvest site hematomas developed in 2 patients, postoperative loss of knee extension in 4 patients, and graft failure in 11 patients. No significant differences in quadriceps or hamstrings LSIs were noted between patients with previous hamstring versus patella tendon autografts (P > .050). CONCLUSION: Revision ACLR with all-soft tissue QT autografts has acceptable early and intermediate-term outcomes with reasonable complication rates (11/80 patients with follow-up). Secondary insult to the extensor mechanism via QT autograft harvest does not adversely affect strength after prior patellar tendon versus hamstring autograft. LEVEL OF EVIDENCE: Level IV, cases series subgroup analysis.

Terminal knee extension deficit and female sex predict poorer quadriceps strength following ACL reconstruction using all-soft tissue quadriceps tendon autografts.

PURPOSE: The all-soft tissue quadriceps tendon (QT) autograft is becoming increasingly popular for ACL reconstruction (ACLR); however, studies reporting strength recovery and early outcomes after QT autograft are limited with patient samples composed of predominantly males. The primary purpose was to characterize early, sex-specific recovery of strength, range of motion (ROM), and knee laxity in a large cohort of patients undergoing primary ACLR with standardized harvest technique of the all-soft tissue QT autograft. The secondary purpose was to examine the influence of demographic factors and clinical measures on 6-month quadriceps strength. METHODS: Patients 14-25 years who underwent primary, unilateral ACLR with all-soft tissue QT autografts were prospectively followed. Knee laxity and ROM were collected at 6 weeks, 3 and 6 months; while, quadriceps normalized torques and limb symmetry indices (LSI) were collected at 3 and 6 months using isokinetic dynamometry at 60°/s. Two-way ANOVAs with repeated measures were conducted to determine recovery over time and between sexes. Stepwise linear multiple regressions were conducted to determine predictors of 6-month quadriceps strength. RESULTS: Three-hundred and twenty patients were included (18 ± 3 years; 156 males:164 females; BMI = 24 ± 4 kg/m2) with no early graft failures within the study period. For strength, there were significant main effects of time (p < 0.001) and sex (p < 0.001), indicating similar improvement from 3 to 6 months with males demonstrating greater quadriceps LSI (6 months: 72.1 vs 63.3%) and normalized strength (6 months: 2.0 vs 1.6 Nm/kg). A significantly higher proportion of females had knee extension ROM deficits ≥ 5° compared to males at 6 weeks (61 vs 39%; p = 0.002). Female sex and 3-month extension ROM deficits were identified as significant predictors of 6-month quadriceps LSI (R2 = 0.083; p < 0.001). Female sex, BMI, and 6-week extension ROM deficits were identified as significant predictors of 6-month normalized quadriceps strength (R2 = 0.190; p < 0.001). CONCLUSIONS: Females had decreased quadriceps strength and greater extension ROM deficits at 3 and 6 months following ACLR using all-soft tissue QT autografts. Female sex, higher BMI, and loss of extension ROM were independent predictors of poorer quadriceps strength at 6 months. There were no early graft failures, and laxity remained within normal ranges for both males and females. Surgeons and rehabilitation clinicians should be aware of the increased risk of postoperative loss of extension ROM in females and its implications on quadriceps strength recovery. LEVEL OF EVIDENCE: III.

Editorial Commentary: Considering Fatigue When Assessing Athletes for Dynamic Knee Valgus: Is This the Next Big Step in Identifying Anterior Cruciate Ligament Injury Risk?

Excessive dynamic knee valgus during jumping is a poor movement strategy that has been well-documented as a risk factor for anterior cruciate ligament injury. Yet, there has been little progress in the translation of findings from high-tech motion capture laboratories to clinically applicable settings. One barrier to widespread use is expensive technology that requires time; therefore, field-based efficient assessment tools that can be used by several types of clinicians are desperately needed. Further, fatigue can influence dynamic knee valgus and should be considered when assessing or conditioning athletes.

Quadriceps Recovery After Anterior Cruciate Ligament Reconstruction With Quadriceps Tendon Versus Patellar Tendon Autografts.

BACKGROUND: Quadriceps tendon (QT) autografts are being increasingly used for anterior cruciate ligament reconstruction (ACLR). A paucity of studies exist that compare QT autografts with alternative graft options. Additionally, concerns exist regarding quadriceps recovery after graft harvest insult to the quadriceps muscle-tendon unit. PURPOSE/HYPOTHESIS: The purpose of this study was to compare quadriceps recovery and functional outcomes in patients with QT versus bone-patellar tendon-bone (BPTB) autografts. The hypothesis was that those with QT autografts would demonstrate superior outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Active patients with a history of primary, unilateral ACLR with soft tissue QT or BPTB autografts participated. Quadriceps recovery was quantified using variables of strength, muscle size, and activation. Knee extensor isometric and isokinetic strength was measured bilaterally with an isokinetic dynamometer and normalized to body weight. Quadriceps activation was measured with the superimposed burst technique. The maximal cross-sectional area of each quadriceps muscle was measured bilaterally using magnetic resonance imaging. Assessors of muscle size were blinded to the graft type and side of ACLR. Functional tests included hop tests and step length symmetry during walking, measured via spatiotemporal gait analysis. Self-reported function was determined with the International Knee Documentation Committee (IKDC) questionnaire. Neuromuscular and functional outcomes were expressed as limb symmetry indices (LSIs: [surgical limb/nonsurgical limb]*100%). Wilcoxon rank-sum tests were used to compare the LSIs and IKDC scores between groups. RESULTS: There were 30 study participants (19 male, 11 female; median age, 22 years [range, 14-41 years]; median time since surgery, 8 months [range, 6-23 months]), with 15 patients in each group. There were no significant between-group differences in demographic variables or outcomes. LSIs were not significantly different between the QT versus BPTB group, respectively: knee extensor isokinetic strength at 60 deg/s (median, 70 [range, 41-120] vs 68 [range, 37-83]; P = .285), activation (median, 95 [range, 85-111] vs 92 [range, 82-105]; P = .148), cross-sectional area of the vastus medialis (median, 79 [range, 62-104] vs 77 [range, 62-95]; P = .425), single-leg hop test (median, 88 [range, 35-114] vs 77 [range, 49-100]; P = .156), and step length symmetry (median, 99 [range, 93-104] vs 98 [range, 92-103]; P = .653). The median IKDC scores between the QT and BPTB groups were also not significantly different: 82 (range, 67-94) versus 83 (range, 54-94); respectively (P = .683). CONCLUSION: Patients with QT autografts demonstrated similar short-term quadriceps recovery and postsurgical outcomes compared with patients with BPTB autografts.

Progesterone Inhibits basal and gonadotropin-releasing hormone induction of luteinizing hormone beta-subunit gene expression.

LH and FSH play critical roles in mammalian reproduction by mediating steroidogenesis and gametogenesis in the gonad. Gonadal steroid hormone feedback to the hypothalamus and pituitary influences production of the gonadotropins. We previously demonstrated that progesterone differentially regulates the expression of the LH and FSH beta-subunits at the level of the gonadotrope: FSHbeta transcription is induced, whereas LHbeta is repressed. In this study, we investigated the mechanism of progesterone repression of LHbeta gene expression using immortalized gonadotrope-derived LbetaT2 cells. The progesterone suppression of both basal and GnRH-induced LHbeta gene expression occurs in a hormone- and receptor-dependent manner. Chromatin immunoprecipitation demonstrates that the hormone-bound progesterone receptor (PR) is recruited to the endogenous mouse LHbeta promoter. In addition, suppression requires both the amino-terminal and DNA-binding regions of PR. Furthermore, progesterone suppression does not require direct PR binding to the promoter, and, thus, PR is likely recruited to the promoter via indirect binding through other transcription factors. These data demonstrate that the molecular mechanism for progesterone action on the LHbeta promoter is distinct from FSHbeta, which involves direct PR binding to the promoter to produce activation. It also differs from androgen repression of LHbeta gene expression in that, rather than Sp1 or steroidogenic factor-1 elements, it requires elements within -300/-250 and -200/-150 that also contribute to basal expression of the LHbeta promoter. Altogether, our data indicate that progesterone feedback at the level of the pituitary gonadotrope is likely to play a key role in differential production of the gonadotropin genes.