The Effect of Minor Adjustments to Tibial and Femoral Component Position on Soft Tissue Balance in Robotic Total Knee Arthroplasty.

BACKGROUND: Ideal goals for alignment and balance in total knee arthroplasty (TKA) remain controversial. We aimed to compare initial alignment and balance using mechanical alignment (MA) and kinematic alignment (KA) techniques and to analyze the percentage of knees that could achieve balance using limited adjustments to component position. METHODS: Prospective data on 331 primary robotic TKAs (115 MAs and 216 KAs) were analyzed. Medial and lateral virtual gaps were recorded in both flexion and extension. A computer algorithm was used to calculate potential (theoretical) implant alignment solutions to achieve balance within 1 millimeter (mm) without soft tissue release given an alignment philosophy (MA or KA), angular boundaries (±1, ±2, or ±3°), and gap targets (equal gaps or lateral laxity allowed). The percentage of knees that could theoretically achieve balance was compared. RESULTS: Less than 5% of TKAs were initially balanced. Limited adjustments to component position increased the percentage of TKAs that could be balanced in a graduated manner, with no difference between MA and KA start points: adjustments of ±1 (10% versus 6%, P = .17), ±2 (42% versus 39%, P = .61), or of ±3 (54% versus 51%, P = .66). A higher percentage of TKAs could be balanced when a greater range for lateral gap laxity was allowed. Balancing from KA resulted in increased joint line obliquity in the final implant alignment. CONCLUSION: A high percentage of TKAs can be balanced without soft tissue release using minor adjustments to component position. Surgeons should consider the relationship between alignment and balance goals when optimizing component positioning in TKA.

The Knee-Fix study: study protocol for a randomised controlled trial evaluating cemented and cementless components in total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is an effective procedure for patients with a variety of knee conditions. The main cause of aseptic TKA failure is implant loosening, which has been linked to poor cement mantle quality. Cementless components were introduced to offer better longer-term biological fixation through osseointegration; however, early designs led to increased rate of revision due to a lack of initial press-fit and bony ingrowth. Newer highly porous metal designs may alleviate this issue but randomised data of fully uncemented TKA (tibial, femoral, patella) is lacking. The aim of the Knee-Fix study is to investigate the long-term implant survival and patient outcomes of fully uncemented compared with cemented fixation in TKA. Our study hypothesis was that uncemented TKA would be as clinically reliable and durable as the gold-standard cemented TKA. METHODS: The Knee-Fix study is a two-arm, single-blinded, non-inferiority randomised controlled trial with 160 patients in each arm and follow-up at 6 weeks, 6 months, 12 months, 24 months, 5 years and 10 years. The primary outcome of interest is implant fixation, which will be measured by assessment of postoperative progressive radiolucencies with the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Secondary outcome measures are patient-reported outcomes, measured using Oxford Knee Score (OKS), International Knee Society System (IKSS), Forgotten Joint Score-12 (FJS-12), EuroQol (EQ-5D-5L), VAS Pain, Patient Satisfaction Score and Net Promoter Score. DISCUSSION: While cemented fixation remains the gold standard, a growing proportion of TKA are now implanted cementless. Highly porous metal cementless components for TKA can offer several benefits including potentially improved biological fixation; however, long-term outcomes need further investigation. This prospective study will help discern long-term differences between the two techniques. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001624471 . Registered trial name: Knee-Fix study (Cemented vs Uncemented Total Knee Replacement). Registered on 24 November 2016.

Robotic-arm assisted total knee arthroplasty has a learning curve of 16 cases and increased operative time of 12 min.

BACKGROUND: Robotic-arm assisted systems are increasingly used for knee arthroplasty, however introduction of new systems can involve a learning curve. We aimed to define the learning curve in terms of operative time and component placement/sizing of a robotic system for total knee arthroplasty (TKA) in a team of experienced surgeons, and to investigate mid-term patient outcomes. METHODS: A total of 101 consecutive patients underwent primary robotic-arm assisted TKA by three surgeons (mean 2 year follow-up). Operative times, component placement, implant sizing and reoperations were recorded. Cumulative Summation (CUSUM) was used to analyse learning curves. Patient outcomes were compared between learning and proficiency phases. RESULTS: The learning curve was 16 cases, with a 12-min increase in operative time (P < 0.01). Once proficiency was achieved, the greatest time reductions were seen for navigation registration (P = 0.003) and bone preparation (P < 0.0001). A learning curve was found with polyethylene (PE) insert sizing (P = 0.01). No differences were found between learning and proficiency groups in terms of implant survival (100% and 97%, respectively, NS) or patient-reported outcome measures at 2 years (NS). CONCLUSION: Introduction of a robotic-arm assisted system for TKA led to increased operative times for navigation registration and bone preparation, and a learning curve with PE insert sizing. No difference in patient outcomes between learning and proficiency groups at 2 years was found. These findings can inform surgeons' expectations when starting to use robotic-assisted systems.

No Difference in 5-year Clinical or Radiographic Outcomes Between Kinematic and Mechanical Alignment in TKA: A Randomized Controlled Trial.

BACKGROUND: In kinematic alignment in TKA, the aim is to match the implant's position to the pre-arthritic anatomy of an individual patient, in contrast to the traditional goal of neutral mechanical alignment. However, there are limited mid-term, comparative data for survivorship and functional outcomes for these two techniques. QUESTIONS/PURPOSES: In the setting of a randomized, controlled trial at 5 years, is there a difference between kinematic alignment and mechanical alignment in TKA in terms of (1) patient-reported outcome measures, (2) survivorship free from revision or reoperation, and (3) the incidence of radiographic aseptic loosening? METHODS: In the initial study, 99 primary TKAs for osteoarthritis were randomized to either the mechanical alignment (n = 50) or kinematic alignment (n = 49) group. Computer navigation was used in the mechanical alignment group, and patient-specific cutting blocks were used in the kinematic alignment group. At 5 years, 95% (48 of 50) of mechanical alignment and 96% (47 of 49) of kinematic alignment TKAs were available for follow-up. Knee function was assessed using the Knee Society Score (KSS), VAS, Oxford Knee Score (OKS), WOMAC, Forgotten Joint Score (FJS) and EuroQol 5D. Survivorship free from reoperation (any reason) and revision (change or addition of any component) was determined via Kaplan-Meier analysis. Radiographs were assessed for signs of aseptic loosening (as defined by the presence of progressive radiolucent lines in two or more zones) by a single blinded observer. RESULTS: At 5 years, there were no differences in any patient-reported outcome measure between the two groups. For example, the mean OKS did not differ between the two groups (kinematic alignment: 41.4 ± 7.2 versus mechanical alignment: 41.7 ± 6.3; difference -0.3 [95% confidence interval - 3.2 to 2.5]; p = 0.99). At 5 years, survivorship free from reoperation was 92.2 (95% CI 80.4 to 97.0) for mechanical alignment and 89.7 (95% CI 77.0 to 95.6) for kinematic alignment (log rank test; p = 0.674), survivorship free from revision was 94.1 (95% CI 82.9 to 98.1) for mechanical alignment and 95.9 (95% CI 84.5 to 99.0) for kinematic alignment (log rank test; p = 0.681). At 5 years, one patient demonstrated radiographic aseptic loosening for the mechanical alignment group; no cases were identified for the kinematic alignment group. CONCLUSIONS: We found no mid-term functional or radiographic differences between TKAs with mechanical alignment or kinematic alignment. The anticipated improvements in patient-reported outcomes with kinematic alignment were not realized. Because kinematic alignment results in a high proportion of patients whose tibial components are inserted in varus, loosening remains a potential long-term concern. Given the unknown impact on long-term survivorship of the substantial alignment alterations with kinematic alignment, our findings do not support the routine use of kinematic alignment outside of a research setting. LEVEL OF EVIDENCE: Level I, therapeutic study.

Post-operative mortality rates for neck of femur fracture at Waitemata District Health Board.

AIM: Mortality rates of up to 38% at one year have been reported following surgery for neck of femur fractures. The aim of this review is to evaluate the post-operative mortality rates and trends over time for patients with fractured neck of femur at Waitemata District Health Board. METHOD: A retrospective cohort study of all patients who received surgery following a neck of femur fracture at Waitemata District Health Board between 2009 and 2016. Inpatient data was retrieved from electronic hospital records and mortality rates from the Ministry of Health, New Zealand. Analyses included crude mortality rates and trends over time, and time-to-theatre from presentation with neck of femur fracture. RESULTS: A total of 2,822 patients were included in the study; mean age 81.9 years, 70.4% female and 29.6% male. Overall post-operative crude rates for inpatient, 30-day and one-year mortality were 3.7%, 7.2% and 23.8% respectively. Adjusted analyses showed a statistically significant decrease in mortality rates between 2009 and 2016 at inpatient (p=0.001), 30 days (p=<0.001) and one year (p=<0.001) time periods. There was also a significant association between time-to-theatre and mortality at inpatient (p=0.002), 30 days (p=0.0001), and one year (p=0.0002) time periods. CONCLUSION: Mortality rates following surgery for fractured NOF have significantly improved over recent years at Waitemata District Health Board. Reduced time-to-theatre is associated with decreased inpatient, 30-day and one-year mortality.

Safety of non-ablative fractional laser for acne scars within 1 month after treatment with oral isotretinoin: A randomized split-face controlled trial.

BACKGROUND AND OBJECTIVE: Based on reports of poor wound healing and scarring, it is currently recommended that patients wait 6 months after completion of oral isotretinoin therapy before the safe initiation of laser treatment. Our aim was to evaluate the safety of non-ablative fractional laser (NAFL) treatment for acne scars within 1 month after isotretinoin therapy. STUDY DESIGN/METHODS: This was a randomized split-face controlled trial involving 10 patients with acne scars who had completed isotretinoin treatment. All patients received three treatments each spaced 4 weeks apart with an erbium-doped 1550 nm NAFL on one side of the face within 1 month after isotretinoin therapy. The untreated side acted as a control. Wound healing and adverse effects as well as acne scar improvement were evaluated by two blinded dermatologists. RESULTS: All patients demonstrated normal wound healing post NAFL treatments, and neither hypertrophic scars nor keloids were observed. Acne scar improvement was satisfactory. CONCLUSION: NAFL treatment for acne scarring appears to be well tolerated within 1 month of completing isotretinoin treatment. Dermatologists should reevaluate the current recommendation to wait 6 months after isotretinoin treatment for acne scar revision with lasers. Other larger studies are necessary to further challenge this dogma. Lasers Surg. Med. 49:886-890, 2017. © 2017 Wiley Periodicals, Inc.

The Chitranjan S. Ranawat Award : No Difference in 2-year Functional Outcomes Using Kinematic versus Mechanical Alignment in TKA: A Randomized Controlled Clinical Trial.

BACKGROUND: Neutral mechanical alignment (MA) in total knee arthroplasty (TKA) aims to position femoral and tibial components perpendicular to the mechanical axis of the limb. In contrast, kinematic alignment (KA) attempts to match implant position to the prearthritic anatomy of the individual patient with the aim of improving functional outcome. However, comparative data between the two techniques are lacking. QUESTIONS/PURPOSES: In this randomized trial, we asked: (1) Are 2-year patient-reported outcome scores enhanced in patients with KA compared with an MA technique? (2) How does postoperative component alignment differ between the techniques? (3) Is the proportion of patients undergoing reoperation at 2 years different between the techniques? METHODS: Ninety-nine primary TKAs in 95 patients were randomized to either MA (n = 50) or KA (n = 49) groups. A pilot study of 20 TKAs was performed before this trial using the same patient-specific guides positioning in kinematic alignment. In the KA group, patient-specific cutting blocks were manufactured using individual preoperative MRI data. In the MA group, computer navigation was used to ensure neutral mechanical alignment accuracy. Postoperative alignment was assessed with CT scan, and functional scores (including the Oxford Knee Score, WOMAC, and the Forgotten Joint Score) were assessed preoperatively and at 6 weeks, 6 months, and 1 and 2 years postoperatively. No patients were lost to followup. We set sample size at a minimum of 45 patients per treatment arm based on a 5-point improvement in the mean Oxford Knee Score (OKS; the previously reported minimum clinically significant difference for the OKS in TKA), a pooled SD of 8.3, 80% power, and a two-sided significance level of 5%. RESULTS: We observed no difference in 2-year change scores (postoperative minus preoperative score) in KA versus MA patients for the OKS (mean 21, SD 8 versus 20, SD 8, least square means 1.0, 95% confidence interval [CI], -1.4 to 3.4, p = 0.4), WOMAC score (mean 38, SD 18 versus 35, SD 8, least square means 3, 95% CI, -3.2 to 8.9, p = 0.3), or Forgotten Joint score (28 SD 37 versus 28, SD 28, least square means 0.8, 95% CI, -9.1-10.7, p = 0.8). Postoperative hip-knee-ankle axis was not different between groups (mean KA 0.4° varus SD 3.5 versus MA 0.7° varus SD 2.0), but in the KA group, the tibial component was a mean 1.9° more varus than the MA group (95% CI, 0.8°-3.0°, p = 0.003) and the femoral component in 1.6° more valgus (95% CI, -2.5° to -0.7°, p = 0.003). Complication rates were not different between groups. CONCLUSIONS: We found no difference in 2-year patient-reported outcome scores in TKAs implanted using the KA versus an MA technique. The theoretical advantages of improved pain and function that form the basis of the design rationale of KA were not observed in this study. Currently, it is unknown whether the alterations in component alignment seen with KA will compromise long-term survivorship of TKA. In this study, we were unable to demonstrate an advantage to KA in terms of pain or function that would justify this risk. LEVEL OF EVIDENCE: Level I, therapeutic study.

Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules.

Cytoplasmic dynein is a dimeric AAA(+) motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA(+) rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein's directionality and unusual stepping behaviour.

Three-dimensional electron microscopy reconstruction and cysteine-mediated crosslinking provide a model of the type III secretion system needle tip complex.

Type III secretion systems are found in many Gram-negative bacteria. They are activated by contact with eukaryotic cells and inject virulence proteins inside them. Host cell detection requires a protein complex located at the tip of the device's external injection needle. The Shigella tip complex (TC) is composed of IpaD, a hydrophilic protein, and IpaB, a hydrophobic protein, which later forms part of the injection pore in the host membrane. Here we used labelling and crosslinking methods to show that TCs from a ΔipaB strain contain five IpaD subunits while the TCs from wild-type can also contain one IpaB and four IpaD subunits. Electron microscopy followed by single particle and helical image analysis was used to reconstruct three-dimensional images of TCs at ∼ 20 Å resolution. Docking of an IpaD crystal structure, constrained by the crosslinks observed, reveals that TC organisation is different from that of all previously proposed models. Our findings suggest new mechanisms for TC assembly and function. The TC is the only site within these secretion systems targeted by disease-protecting antibodies. By suggesting how these act, our work will allow improvement of prophylactic and therapeutic strategies.

Expression of masticatory-specific isoforms of myosin heavy-chain, myosin-binding protein-C and tropomyosin in muscle fibers and satellite cell cultures of cat masticatory muscle.

We test the hypothesis that cat jaw satellite cells belong to a distinct lineage preprogrammed to express masticatory-specific isoforms of myosin heavy-chain (m-MyHC), myosin-binding protein-C (m-MBP-C), and tropomyosin (m-Tm) during myogenesis in vitro. A monoclonal antibody (MAb) against m-MyHC and MAbs raised here against cat m-MBP-C and m-Tm were used to stain cryostat sections of cat masseter muscle and cultured myotubes derived from satellite cells of cat temporalis and limb muscles, using peroxidase immunohistochemistry. MAbs against m-MBP-C bound purified m-MBP-C in Western blots. MAbs against m-Tm failed to react with m-Tm in Western blots, but reacted with native m-Tm in gel electrophoresis-derived ELISA. In cat masseter sections, MAbs against m-MyHC, m-MBP-C, and m-Tm stained all masticatory fibers, but not the jaw-slow fibers. Cat jaw and limb muscle cultures mature significantly more slowly relative to rodent cultures. However, at 3 weeks, all three MAbs extensively stained temporalis myotubes, whereas they apparently stained isolated myotubes weakly in cat limb and rat jaw cultures. We conclude that satellite cells of masticatory fibers are preprogrammed to express these isoforms during myogenesis in vitro. These results consolidate the notion that masticatory and limb muscle allotypes are distinct.

A FERM domain autoregulates Drosophila myosin 7a activity.

Full-length Drosophila myosin 7a (myosin 7a-FL) has a complex tail containing a short predicted coiled coil followed by a MyTH4-FERM domain, an SH3 domain, and a C-terminal MyTH4-FERM domain. Myosin 7a-FL expressed in Sf9 cells is monomeric despite the predicted coiled coil. We showed previously that Subfragment-1 (S1) from this myosin has MgATPase of V(max) approximately 1 s(-1) and K(ATPase) approximately 1 microM actin. We find that myosin 7a-FL has V(max) similar to S1 but K(ATPase) approximately 30 microM. Thus, at low actin concentrations (5 microM), the MgATPase of S1 is fully activated, whereas that of myosin 7a-FL is low, suggesting that the tail regulates activity. Electron microscopy of myosin 7a-FL with ATP shows the tail is tightly bent back against the motor domain. Myosin 7a-FL extends at either high ionic strength or without ATP, revealing the motor domain, lever, and tail. A series of C-terminal truncations show that deletion of 99 aa (the MyTH7 subdomain of the C-terminal FERM domain) is sufficient to abolish bending, and the K(ATPase) is then similar to S1. This region is highly conserved in myosin 7a. We found that a double mutation in it, R2140A-K2143A, abolishes bending and reduces K(ATPase) to S1 levels. In addition, the expressed C-terminal FERM domain binds actin with K(d) approximately 30 microM regardless of ATP, similar to the K(ATPase) value for myosin 7a-FL. We propose that at low cellular actin concentrations, myosin 7a-FL is bent and inactive, but at high actin concentrations, it is unfolded and active because the C-terminal FERM domain binds to actin.