Can a Total Knee System Providing 1 mm Increment of Polyethylene Insert Thickness Offer a Clinical Benefit?

Background and Objectives: The purpose of this study was to compare clinical outcomes and polyethylene (PE) insert thickness between total knee arthroplasty (TKA) systems providing 1 mm and 2 mm increments. Materials and Methods: In this randomized controlled trial, 50 patients (100 knees) undergoing same-day or staggered bilateral TKA were randomized to receive a TKA system providing 1 mm increments in one knee (1 mm group) and a TKA system providing 2 mm increments in the other knee (2 mm group). At 2 years postoperatively, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Forgotten Joint Score (FJS), range of motion (ROM), and insert thicknesses were compared between the groups. Results: A total of 47 patients (94 knees) participated in follow-up analysis. In each group, patient-reported outcomes improved significantly after TKA (all, p < 0.05). There were no significant differences in patient-reported outcomes. The mean ROM was not significantly different between groups at preoperative and 2-year points. The rate of postoperative flexion contracture ≥ 5° was 2.1% and 4.3%, and the rate of postoperative recurvatum ≥ 5° was 4.3% and 2.1% in the 1 mm group and 2 mm, respectively (all, p = 1.000). Mean insert thickness was significantly thinner in the 1 mm group than the 2 mm group (p = 0.001). The usage rate of a thick insert (≥14 mm) was 12.7% and 38.3% in the 1 mm group and 2 mm group (p = 0.005). Conclusions: The use of a TKA system providing 1 mm PE insert thickness increments offered no clinical benefit in terms of patient reported outcomes over systems with 2 mm increments at 2 years of follow-up. However, the TKA system with 1 mm increments showed significantly thinner PE insert usage. As a theoretical advantage of 1 mm increments has yet to be proven, the mid- to long-term effects of thinner PE insert usage must be determined.

Viral dissemination and immune activation modulate antiretroviral drug levels in lymph nodes of SIV-infected rhesus macaques.

Introduction and methods: To understand the relationship between immunovirological factors and antiretroviral (ARV) drug levels in lymph nodes (LN) in HIV therapy, we analyzed drug levels in twenty-one SIV-infected rhesus macaques subcutaneously treated with daily tenofovir (TFV) and emtricitabine (FTC) for three months. Results: The intracellular active drug-metabolite (IADM) levels (TFV-dp and FTC-tp) in lymph node mononuclear cells (LNMC) were significantly lower than in peripheral blood mononuclear cells (PBMC) (P≤0.005). Between Month 1 and Month 3, IADM levels increased in both LNMC (P≤0.001) and PBMC (P≤0.01), with a steeper increase in LNMC (P≤0.01). The viral dissemination in plasma, LN, and rectal tissue at ART initiation correlated negatively with IADM levels at Month 1. Physiologically-based pharmacokinetic model simulations suggest that, following subcutaneous ARV administration, ART-induced reduction of immune activation improves the formation of active drug-metabolites through modulation of kinase activity and/or through improved parent drug accessibility to LN cellular compartments. Conclusion: These observations have broad implications for drugs that need to phosphorylate to exert their pharmacological activity, especially in the settings of the pre-/post-exposure prophylaxis and efficacy of antiviral therapies targeting pathogenic viruses such as HIV or SARS-CoV-2 replicating in highly inflammatory anatomic compartments.

Quantitative PET imaging of the CD4 pool in nonhuman primates.

PURPOSE: Previous SPECT and PET semi-quantitative in vivo imaging studies in monkeys have demonstrated specific uptake of radiolabeled rhesus recombinant anti-CD4 monoclonal antibody fragment CD4R1-F(ab΄)2 in the spleen and clusters of lymph nodes (LNs) but yielded conflicting results of imaging the gut CD4 + T-cell pool. Here, using PET dynamic imaging with kinetic analysis, we performed a fully quantitative CD4 imaging in rhesus macaques. METHODS: The biodistributions of [89Zr]Zr-CD4R1-F(ab΄)2 and/or of [89Zr]Zr-ibalizumab were performed with static PET scans up to 144 h (6 days) post-injection in 18 rhesus macaques with peripheral blood CD4 + T cells/µl ranging from ~ 20 to 2400. Fully quantitative analysis with a 4-h dynamic scan, arterial sampling, metabolite evaluation, and model fitting was performed in three immunocompetent monkeys to estimate the binding potential of CD4 receptors in the LNs, spleen, and gut. RESULTS: The biodistributions of [89Zr]Zr-CD4R1-F(ab΄)2 and [89Zr]Zr-ibalizumab were similar in lymphoid tissues with a clear delineation of the CD4 pool in the LNs and spleen and a significant difference in lymphoid tissue uptake between immunocompetent and immunocompromised macaques. Consistent with our previous SPECT imaging of [99mTc]Tc-CD4R1-F(ab΄)2, the [89Zr]Zr-CD4R1-F(ab΄)2 and [89Zr]Zr-Ibalizumab uptakes in the gut were low and not different between uninfected and SIV-infected CD4-depleted monkeys. Ex vivo studies of large and small intestines confirmed the in vivo images. CONCLUSION: The majority of specific binding to CD4 + tissue was localized to LNs and spleen with minimal uptake in the gut. Binding potential derived from fully quantitative studies revealed that the contribution of the gut is lower than the spleen's contribution to the total body CD4 pool.

Polymeric microfluidic continuous flow mixer combined with hyperspectral FT-IR imaging for studying rapid biomolecular events.

Early reaction intermediates in protein folding, such as those resulting in ß-amyloid formation due to transient misfolding, emerge within a few hundred microseconds. Here, we report a method to obtain sub-millisecond temporal resolution and molecular structural information of protein (mis-)folding events by using a microfluidic continuous-flow mixer (MCFM) in combination with Fourier transform infrared (FT-IR) imaging. The MCFMs are made out of cyclic olefin copolymer (COC) films, because this approach allows for rapid prototyping of different mixer designs. Furthermore, COC offers high IR transparency between 1500 and 2500 cm-1, thus maximizing the signal to noise ratio of the IR data obtained from a sample of interest. By combining narrow and wide channel widths in MCFM design, the platform provides fast mixing (460 µs) to induce protein (mis-)folding, and it maximizes the residence time in the observing area, so a wide range of reaction timescales can be captured in a single image. We validated the platform for its ability to induce and observe sub-millisecond processes by studying two systems: (i) the mixing of H2O and D2O and (ii) the mixing induced deprotonation of carboxylic acid. First, we observed excellent agreement between simulated and experimental data of the on-chip mixing of H2O and D2O, which verifies the distance-reaction time relationships based on simulation. Second, deprotonation of carboxylic acid by on-chip mixing with sodium hydroxide solution validates the ability of the platform to induce rapid pH jump that is needed for some biomolecular reactions. Finally, we studied the methanol-induced partial-unfolding of ubiquitin to show that our platform can be used to study biomolecular events 'on-pathway' using FT-IR imaging. We successfully extracted kinetic and structural details of the conformational changes along the channel. Our results are in agreement with prior studies that required more elaborate stopped flow approaches to acquire data for different time points. In summary, the reported method uses an easy-to-fabricate microfluidic mixer platform integrated with hyperspectral FT-IR imaging for rapid acquisition of structural details and kinetic parameters of biomolecular reactions. This approach does not need stopped flow or molecular imaging probes, as required respectively for alternative FT-IR spectroscopy and fluorescence approaches.

Is It Safe to Inject Corticosteroids Into the Glenohumeral Joint After Arthroscopic Rotator Cuff Repair?

BACKGROUND: Injection of intra-articular corticosteroids is effective for improving the recovery of range of motion (ROM) and pain in various conditions of the shoulder but its use is limited after rotator cuff repair owing to concern over the possible harmful effects of steroids on the repaired tendon. PURPOSE: To evaluate the effect of intra-articular corticosteroid injections on the clinical outcomes and cuff integrity of patients after rotator cuff repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Between March 2011 and April 2014, 80 patients with a small- to medium-sized rotator cuff tear were enrolled in this study and underwent arthroscopic rotator cuff repair. Forty patients received an injection of triamcinolone (40 mg) and lidocaine (1.5 mL) into the glenohumeral joint 8 weeks after surgery (group 1), while the remaining 40 patients received normal saline injection (group 2). Outcome measures-including ROM, American Shoulder and Elbow Surgeons (ASES) score, Constant score, pain visual analog scale, and Simple Shoulder Test score-were evaluated at 3, 6, and 12 months after surgery and at the last follow-up. The integrity of the repaired tendon was evaluated by magnetic resonance imaging (MRI) and classified per Sugaya classification at 8 weeks (before injection) and 12 months after surgery. RESULTS: The mean follow-up period was 25.7 months. At 3 months postoperatively, patients in group 1 had a significantly higher ROM with respect to forward flexion ( P = .05), external rotation at the side ( P = .05), and external rotation at abduction ( P = .04) as compared with group 2, whereas no significant difference was noted between the groups for internal rotation behind the back ( P = .65). Patients in group 1 had significantly lower visual analog scale pain scores ( P = .02) and higher ASES scores (group 1, 68.90; group 2, 60.28; P = .02) at 3-month follow-up. However, there was no significant difference after 6 months with respect to ROM and ASES scores (group 1, 77.80; group 2, 75.88; P = .33). Retears (Sugaya classification IV and V) were determined by MRI at 12 months and observed in a total of 7 patients (8.8%): 3 from group 1 (7.5%) and 4 from group 2 (10%). No retears were observed on MRI in the remaining 73 patients (91.2%): 37 patients from group 1 and 36 patients from group 2. There was no statistically significant difference in rate of retears between groups ( P = .69). CONCLUSION: Intra-articular injection of corticosteroids after rotator cuff repair does not increase the risk of retears and is thus an effective and safe treatment method for increasing ROM (forward flexion, external rotation) and improving clinical score (ASES) during the early postoperative period of patients undergoing rotator cuff repair.

Traumatic C1-2 rotatory subluxation with dens and bilateral articular facet fractures of C2: A case report.

RATIONALE: To the best of our knowledge, this is an extremely rare case of traumatic C1-2 rotatory subluxation associated with multiple C2 fractures. PATIENT CONCERNS: We report the case of a 63-year-old man with type 2 traumatic C1-2 rotatory subluxation (Fielding and Hawkins classification) associated with type III dens (Anderson and D'Alonzo classification) and bilateral articular facet fractures of C2. This injury occurred as a result of falling down in a drunken state. The patient complained of neck pain and mild degree of torticollis but did not show any neurologic abnormalities. DIAGNOSES: Plain radiographs of cervical spine showed extensive soft tissue swelling, a fracture fragment, disruption of spinolaminar line at C1-2 level, and bony overlapping of right side lateral joint of C1-2. Two- and three-dimensional reconstructed computed tomography scans clearly demonstrated complicated C1-2 combined injury. The atlantodental interval was normal. INTERVENTION: By skull traction and derotation, closed reduction of C1-2 rotatory subluxation with a type III dens and bilateral articular facet fractures of C2 was successfully achieved. He was managed with halovest fixation for 3 months. OUTCOMES: At the 1-year follow-up visit solid fusion and improvement of clinical symptoms were achieved without C1-2 instability. LESSONS: Despite traumatic C1-2 rotatory subluxation associated with multiple C2 fractures, trial of closed reduction should be considered as the first choice of treatment so as to preserve C1-2 motion.