Predictors of a Symptomatic Knee Following ACL Reconstruction: 84 Month Follow Up

Objectives: ACL reconstruction is effective in restoring knee stability and returning a majority of patients to sports. However, these patients remain at a higher risk of developing knee OA and a subset of patients have persistent pain. It is currently unknown what pre-operative and early post-operative measures can be used to help predict outcomes following ACL reconstruction at 7 years. The purpose of this study was to compare clinical data, patient-reported outcomes and imaging findings of knee arthrosis between symptomatic and asymptomatic subject at 84 month follow up after primary ACL reconstruction. Methods: We reviewed prospectively collected data from our previously published randomized controlled trial of outcomes of ACL reconstruction. Clinical, radiographic, and patient-reported outcomes were collected pre-operatively, and at 1,3,5, and 7 years post-operatively. Patient-reported outcome measures included SF-36 and KOOS. Imaging studies were used to evaluate medial joint space width, Osteoarthritis Research Society International (OARSI) radiographic score, and Whole-Organ Magnetic Resonance Imaging Score (WORMS). Symptomatic subjects were defined as those with KOOS-pain subscores, measured at 84 months post-operatively, two standard deviations below the mean for healthy athletic patients with a history of a knee ligament injury. These subjects were compared to the remainder of the study group to identify factors predictive of poor outcomes. Results: patient-report outcome measures were available for 72 patients at 84 month follow up. Of these, 7 subjects had KOOS pain scores less than 72.5 and were considered the symptomatic subgroup. Low pre-operative KOOS-ADL and KOOS-sports subscores were associated with low KOOS pain scores at 7 year follow up. SF-36 scores were lower at most time periods in the symptomatic group. In addition, OARSI scores were worse at 1,5, and 7 years, and WORMS showed greater signs of cartilage injury at 3 and 5 years post operatively in the symptomatic group. Medial joint space width was found to be significantly decreased in symptomatic patients at 7 year follow up. Conclusion: Low preoperative KOOS-ADL and KOOS-sports subscores were found to be associated with worse pain outcomes in primary ACL reconstruction patients at 84 months post-operatively. Additionally, multiple post-operative measures were found to be indicative of the ACL reconstruction patients that would have a symptomatic knee. WORMS collected at 3 and 5 years was shown to identify those subjects that would be symptomatic at 7 years. Also, radiographic changes were evident in this group with significantly decreased medial joint space width relative to control subjects. </jats:sec

Preoperative KOOS and SF-36 Scores Are Associated With the Development of Symptomatic Knee Osteoarthritis at 7 Years After Anterior Cruciate Ligament Reconstruction

Background: Anterior cruciate ligament (ACL) tears are associated with the development of knee osteoarthritis despite ACL reconstruction surgery. However, little evidence is available to determine which patients will develop symptomatic knee osteoarthritis. Purpose: To determine if preoperative outcome measures—KOOS (Knee injury and Osteoarthritis Outcome Score) and SF-36 (36-item Short Form Health Survey)—were associated with the development of a symptomatic knee 7 years after ACL reconstruction. A secondary goal was to examine the relationship between imaging evidence of knee osteoarthritis and development of knee pain. Study Design: Case-control study; Level of evidence, 3. Methods: Prospectively collected data from 72 patients were reviewed with 7-year follow-up after unilateral ACL reconstruction. Patients were divided into symptomatic and asymptomatic groups based on the previously defined KOOS pain ≤72. Demographic variables and preoperative KOOS and SF-36 scores were compared between groups. Radiographic and magnetic resonance imaging data were used to evaluate differences in joint space width, Osteoarthritis Research Society International radiographic score, and the Whole-Organ Magnetic Resonance Imaging Score between groups. Univariate and multivariate analyses were performed to identify potential predictors of pain at 7-year follow-up. Wilcoxon sum rank and t tests were used to compare imaging findings between the symptomatic and asymptomatic patients at 7 years. Results: According to KOOS pain, 7 of the 72 patients available at 7-year follow-up formed the symptomatic group. No differences were found between groups in regard to demographic variables or intraoperative findings. In multivariate analysis, lower preoperative scores for KOOS sports/recreation ( P = .005) and SF-36 mental health ( P = .025) were associated with a painful knee at 7 years, with increased odds of 82% and 68% per 10-unit decrease, respectively. The Whole-Organ Magnetic Resonance Imaging Score at 7 years showed evidence of osteoarthritic changes in the symptomatic group as compared with the asymptomatic group ( P = .047). However, there were no significant differences in the Osteoarthritis Research Society International radiographic score ( P = .051) or joint space width ( P = .488) between groups. Conclusion: Lower preoperative KOOS and SF-36 scores were associated with those patients who developed symptomatic knee osteoarthritis 7 years after ACL reconstruction. </jats:sec

Older Adults in the SeniorWISE Study At Risk for Mild Cognitive Impairment

As part of a larger clinical trial, SeniorWISE(™) (Wisdom Is Simply Exploration), this study provides baseline affective, cognitive, and functional ability data and reports on the likely incidence of mild cognitive impairment (MCI) in a triethnic community sample of older adults (N = 265). Seventy-eight individuals had memory complaints, whereas 105 had none. Of the complainants, 32 had normal memory function and 46 had poor memory performance. Among those without memory complaints, 42 had no memory impairment and 63 had poor memory performance. Forty-six individuals (17%) met the criteria of poor everyday memory functioning and memory complaints whereas 81 (31%) would be considered to be at risk based on other MCI criteria. This pattern of results suggests that those with declining memory are less aware of their deficits in activities of daily living that their actual performance would suggest are occurring

Early success of the arthroscopic-assisted locked loop suprapectoral biceps tenodesis

Background: There is wide variability in surgical technique for biceps tenodesis. Prior biomechanical studies have demonstrated superior ultimate and fatigue strength with a Krakow-type locked loop when compared with simple suture and lasso-loop configurations; however, this had not yet been clinically studied. The purpose of this study was to assess the short-term results an arthroscopic-assisted locked loop (ALL) suprapectoral biceps tenodesis technique. Methods: All patients who underwent an ALL suprapectoral biceps tenodesis by a single surgeon from 2012 and 2019 with a minimum of 12-month follow-up were analyzed. Data collected included demographics, surgical indications, concomitant operative procedures, and postoperative complications of anterior shoulder “groove” pain, “Popeye deformity,” biceps muscle cramping pain, and need for revision surgery. Results: Forty patients who underwent an ALL suprapectoral biceps tenodesis met inclusion criteria. Patients were 55.6 ± 8.6 years of age, consisting of 28 men (57%) and 21 women (43%). The median follow-up was 19.3 months. At the latest follow-up, 1 (2%) patient had anterior shoulder “groove” pain, and no patients had a Popeye deformity or biceps muscle cramping. There were no revision biceps tenodesis procedures. Conclusion: The ALL suprapectoral biceps tenodesis technique results in a low incidence of postoperative complications. At a short-term follow-up of 1 year, no patients had reoperations or revisions for failed biceps tenodesis. Groove pain was nearly absent in this series of patients

A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain

Abstract Background Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. Methods A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. Results Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5–9 days) and mean time of viremia was 6.8 days (range 3–9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. Conclusions We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. Clinical Trials Registration NCT02372175. </jats:sec

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials

Study flow.

Fig outlines the number of subjects who were screened, enrolled, and received each vaccination. A total of three volunteers, one in cohort 1 and two in cohort 2, dropped out for reasons not related to the study.</p

Study design.

<p>Immunization dose and schedule for the three cohorts of ten volunteers who were immunized three times with either a low (15 μg), medium (30 μg) or high (60 μg) dose of the vaccine, VMP001 formulated in AS01_B adjuvant (VMP001/AS01_B). The first 2 immunizations for each cohort were staggered by two weeks in order to monitor vaccine safety. The 2^nd dose was delivered 4 weeks after the 1^st and the 3^rd immunization was performed 8, 6 and 4 weeks post 2^nd dose for cohorts 1 (red), 2 (blue) and 3 (green), respectively. Control and vaccinated subjects were challenged at WRAIR with mosquitoes infected with P. vivax parasites that originated in Thailand.</p