Diagnostic yield of computed tomography in the evaluation of unilateral vocal fold palsy.

BACKGROUND: There is a paucity of Asian-based data regarding the diagnostic yield of computed tomography imaging in the initial assessment of idiopathic unilateral vocal fold palsy. OBJECTIVES: To investigate the diagnostic yield of computed tomography in idiopathic unilateral vocal fold palsy cases in an Asian tertiary hospital, and to determine the causative pathologies and positive predictive factors. METHOD: A retrospective chart review was conducted of patients (between 2010 and 2018) with a clinical diagnosis of idiopathic unilateral vocal fold palsy who underwent contrast-enhanced computed tomography of the neck and chest at Tan Tock Seng Hospital, Singapore. RESULTS: The overall computed tomography diagnostic yield was 21 per cent, with malignancy accounting for 63.6 per cent of diagnoses. Degree of vocal fold weakness was the only significant predictor of positive computed tomography findings (11.5 per cent in vocal fold paresis vs 29.1 per cent in vocal fold paralysis, p = 0.025). None of the patients with negative computed tomography findings went on to develop disease after a mean follow up of 14.3 months. CONCLUSION: Computed tomography is a useful initial investigation for idiopathic unilateral vocal fold palsy, particularly in cases with vocal fold paralysis.

Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial.

BACKGROUND: CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC). METHODS: Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07). CONCLUSIONS: CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509). TRIAL REGISTRATION: NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.

Shod landing provides enhanced energy dissipation at the knee joint relative to barefoot landing from different heights.

Athletic shoes can directly provide shock absorption at the foot due to its cushioning properties, however it remains unclear how these shoes may affect the level of energy dissipation contributed by the knee joint. This study sought to investigate biomechanical differences, in terms of knee kinematics, kinetics and energetics, between barefoot and shod landing from different heights. Twelve healthy male recreational athletes were recruited and instructed to perform double-leg landing from 0.3-m and 0.6-m heights in barefoot and shod conditions. The shoe model tested was Brooks Maximus II. Markers were placed on the subjects based on the Plug-in Gait Marker Set. Force-plates and motion-capture system were used to capture ground reaction force (GRF) and kinematics data respectively. 2×2-ANOVA (barefoot/shod condition×landing height) was performed to examine differences in knee kinematics, kinetics and energetics between barefoot and shod conditions from different landing heights. Peak GRF was not significantly different (p=0.732-0.824) between barefoot and shod conditions for both landing heights. Knee range-of-motion, flexion angular velocity, external knee flexion moment, and joint power and work were higher during shod landing (p<0.001 to p=0.007), compared to barefoot landing for both landing heights. No significant interactions (p=0.073-0.933) were found between landing height and barefoot/shod condition for the tested parameters. While the increase in landing height can elevate knee energetics independent of barefoot/shod conditions, we have also shown that the shod condition was able to augment the level of energy dissipation contributed by the knee joint, via the knee extensors, regardless of the tested landing heights.

Non-linear flexion relationships of the knee with the hip and ankle, and their relative postures during landing.

The knee joint, together with the hip and ankle, contributes to overall shock absorption through their respective flexion motions during landing. This study sought to investigate the presence of a lower extremity coordination pattern by determining mathematical relationships that associate knee flexion angles with hip flexion and ankle dorsiflexion angles during landing phase, and to determine relative postures of the hip and ankle, with reference to the knee, and examine how these relative postures change during key events of the landing phase. Eight healthy male subjects were recruited to perform double-leg landing from 0.6-m height. Motion capture system and force-plates were used to obtain kinematics and ground reaction forces (GRF) respectively. Non-linear regression analysis was employed to determine appropriate mathematical relationships of the hip flexion and ankle dorsiflexion angles with knee flexion angles during the landing phase. Relative lower extremity postures were compared between events of initial contact, peak GRF and maximum knee flexion, using ANOVA on ranks. Our results demonstrated a lower extremity coordination pattern, whereby the knee flexion angles had strong exponential (R(2) = 0.92-0.99, p < 0.001) and natural logarithmic (R(2) = 0.85-0.97, p < 0.001) relationships with hip flexion and ankle dorsiflexion angles respectively during the landing phase. Furthermore, we found that the s ubjects adopted distinctly different relative lower extremity postures (p < 0.05) during peak GRF as compared to initial contact. These relative postures were further maintained till the end of the landing phase. The occurrence of these relative postures may be a reflexive mechanism for the subjects to efficiently absorb the impact imposed by the peak GRF.

Effect of an anterior-sloped brace joint on anterior tibial translation and axial tibial rotation: a motion analysis study.

BACKGROUND: Anterior tibial translation and axial tibial rotation are major biomechanical factors involved in anterior cruciate ligament injuries. This study sought to evaluate a brace prototype designed with an anterior-sloped joint, in terms of its efficacy in attenuating anterior tibial translation and axial tibial rotation during landing, using a motion analysis approach. METHODS: Ten healthy male subjects performed single-leg landing tasks from a 0.6-m height with and without the brace prototype. Ground reaction force and kinematics data were obtained using a motion-capture system and force-plates. Anterior tibial translation and axial tibial rotation were determined based on tibial and femoral marker reference frames. Vertical and anterior-posterior ground reaction forces, hip, knee and ankle joint range-of-motions and angular velocities, anterior tibial translation and axial tibial rotation were compared between unbraced and braced conditions using Wilcoxon signed-rank test. FINDINGS: We found no significant difference in peak vertical and anterior-posterior ground reaction forces (p=0.770 and p=0.332 respectively) between unbraced and braced conditions. Knee joint range-of-motion and angular velocity were lower (p=0.037 and p=0.038 respectively) for braced condition than unbraced condition. Anterior tibial translation and axial tibial rotation were reduced (p=0.027 and p=0.006 respectively) in braced condition, compared to unbraced condition. INTERPRETATION: The anterior-sloped brace joint helps to attenuate anterior tibial translation and axial tibial rotation present in the knee joint during landing. It is necessary to test the brace prototype in a sporting population with realistic sports landing situations in order to assess its effectiveness in lowering anterior cruciate ligament injury risk.

Effects of implantation of bone marrow mesenchymal stem cells, disc distraction and combined therapy on reversing degeneration of the intervertebral disc.

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.

Extent and distribution of tibial osteochondral disruption during simulated landing impact with axial tibial rotation restraint.

Post-traumatic knee osteochondral injuries are often coupled with anterior cruciate ligament (ACL) injury mechanisms during landing. However, it is not well understood whether restraining axial tibial rotation during landing would influence the extent and distribution of osteochondral disruption. Using ski landing as an example, this study subjected knee specimens to simulated landing impact without and with axial tibial rotation restraint, and investigated the extent and distribution of osteochondral disruption at the tibial plateau. Twenty-one porcine knee specimens were randomly divided into three test conditions, namely: (1) control, (2) impact only (I), and 3) impact with restraint (IR). Simulated landing impact was applied to the specimens based on a single 10 Hz haversine. Osteochondral explants were obtained from anterior, middle and posterior regions of medial and lateral tibial compartments. The extent of cartilage and trabecular disruption in these explants was examined based on histology, SEM and microCT. Only specimens in unrestrained condition incurred ACL failure upon impact. Restraining axial tibial rotation during simulated impact generally inflicted cartilage damage and deformation, and further caused trabecular disruption. Axial tibial rotation restraint did not necessarily restrict anterior tibial translation, as indicated by the presence of relative posterior femoral translation and osteochondral disruption at anterior-posterior tibial regions. While the results obtained in the current study may not be completely translatable to human models, there is likelihood that restraining axial tibial rotation during landing may help to prevent ACL failure, but will also induce osteochondral disruption in most tibial regions.

Enhancement of meniscal repair in the avascular zone using mesenchymal stem cells in a porcine model.

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue. At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001). The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced.

Direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact.

Anterior tibial loading is a major factor involved in the anterior cruciate ligament (ACL) injury mechanism during ski impact landing. We sought to investigate the direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact of intact knee joints without quadriceps activation. Twelve porcine knee specimens were procured. Four specimens were used as non-impact control while the remaining eight were mounted onto a material-testing system at 70 degrees flexion and subjected to simulated landing impact, which was successively repeated with incremental actuator displacement. Four specimens from the impacted group underwent pre-impact MRI for tibial plateau angle measurements while the other four were subjected to histology and microCT for cartilage morphology and volume assessment. The tibial plateau angles ranged from 29.4 to 38.8 degrees . There was a moderate linear relationship (Y=0.16X; R(2)=0.64; p<0.001) between peak axial impact compressive load (Y) and peak anterior tibial load (X). The anterior and posterior regions in the impacted group sustained surface cartilage fraying, superficial clefts and tidemark disruption, compared to the control group. MicroCT scans displayed visible cartilage deformation for both anterior and posterior regions in the impacted group. Due to the tibial plateau angle, increased axial impact compressive load can directly elevate anterior tibial load and hence contribute to ACL failure during simulated landing impact. Axial impact compressive load resulted in shear cartilage damage along anterior-posterior tibial plateau regions, due to its contribution to anterior tibial loading. This mechanism plays an important role in elevating ACL stress and cartilage deformation during impact landing.

Sagittal knee joint kinematics and energetics in response to different landing heights and techniques.

Single-leg and double-leg landing techniques are common athletic maneuvers typically performed from various landing heights during intensive sports activities. However, it is still unclear how the knee joint responds in terms of kinematics and energetics to the combined effects of different landing heights and techniques. We hypothesized that the knee displays greater flexion angles and angular velocities, joint power and work in response to the larger peak ground reaction force from 0.6-m height, compared to 0.3-m height. We further hypothesized that the knee exhibits elevated flexion angles and angular velocities, joint power and work during double-leg landing, relative to single-leg landing. Ground reaction force, knee joint kinematics and energetics data were obtained from 10 subjects performing single-leg and double-leg landing from 0.3-m to 0.6-m heights, using motion-capture system and force-plates. Higher peak ground reaction force (p<0.05) was observed during single-leg landing and/or at greater landing height. We found greater knee flexion angles and angular velocities (p<0.05) during double-leg landing and/or at greater landing height. Elevated knee joint power and work were noted (p<0.05) during double-leg landing and/or at greater landing height. The knee joint is able to respond more effectively in terms of kinematics and energetics to a larger landing impact from an elevated height during double-leg landing, compared to single-leg landing. This allows better shock absorption and thus minimizes the risk of sustaining lower extremity injuries.

Effect of landing height on frontal plane kinematics, kinetics and energy dissipation at lower extremity joints.

Lack of the necessary magnitude of energy dissipation by lower extremity joint muscles may be implicated in elevated impact stresses present during landing from greater heights. These increased stresses are experienced by supporting tissues like cartilage, ligaments and bones, thus aggravating injury risk. This study sought to investigate frontal plane kinematics, kinetics and energetics of lower extremity joints during landing from different heights. Eighteen male recreational athletes were instructed to perform drop-landing tasks from 0.3- to 0.6-m heights. Force plates and motion-capture system were used to capture ground reaction force and kinematics data, respectively. Joint moment was calculated using inverse dynamics. Joint power was computed as a product of joint moment and angular velocity. Work was defined as joint power integrated over time. Hip and knee joints delivered significantly greater joint power and eccentric work (p<0.05) than the ankle joint at both landing heights. Substantial increase (p<0.05) in eccentric work was noted at the hip joint in response to increasing landing height. Knee and hip joints acted as key contributors to total energy dissipation in the frontal plane with increase in peak ground reaction force (GRF). The hip joint was the top contributor to energy absorption, which indicated a hip-dominant strategy in the frontal plane in response to peak GRF during landing. Future studies should investigate joint motions that can maximize energy dissipation or reduce the need for energy dissipation in the frontal plane at the various joints, and to evaluate their effects on the attenuation of lower extremity injury risk during landing.

Repeated application of incremental landing impact loads to intact knee joints induces anterior cruciate ligament failure and tibiofemoral cartilage deformation and damage: A preliminary cadaveric investigation.

Anterior cruciate ligament (ACL) injury is a major problem worldwide and prevails during high-impact activities. It is not well-understood how the extent and distribution of cartilage damage will arise from repetitive landing impact loads that can lead to ACL failure. This study seeks to investigate the sole effect of repetitive incremental landing impact loads on the induction of ACL failure, and extent and distribution of tibiofemoral cartilage damage in cadaveric knees. Five cadaveric knees were mounted onto a material testing system at 70 degrees flexion to simulate landing posture. A motion-capture system was used to track rotational and translational motions of the tibia and femur, respectively. Each specimen was compressed at a single 10Hz haversine to simulate landing impact. The compression trial was successively repeated with increasing actuator displacement till a significant compressive force drop was observed. All specimens underwent ACL failure, which was confirmed via magnetic resonance scans and dissection. Volume analysis, thickness measurement and histological techniques were employed to assess cartilage lesion status. For each specimen, the highest peak compressive force (1.9-7.8kN) was at the final trial in which ACL failure occurred; corresponding posterior femoral displacement (7.6-18.0mm) and internal tibial rotation (0.6 degrees -4.7 degrees ) were observed. Significant compressive force drop (79.8-90.9%) was noted upon ACL failure. Considerable cartilage deformation and damage were found in exterior, posterior and interior femoral regions with substantial volume reduction in lateral compartments. Repeated application of incremental landing impact loads can induce both ACL failure and cartilage damage, which may accelerate the risk of developing osteoarthritis.

Prevalence of Penicillium specific Ig E level and allergy symptoms among office workers in a selected company in Bangi, Malaysia.

Indoor fungal reservoirs, particularly airborne Penicillium species, were identified throughout the ventilation system of the building and dissemination of fungi from those reservoirs was found to be occurring all the time. The objectives of this study were to determine the association between air concentration of indoor mould (Penicillium) and allergy symptoms among office workers. The study design used in this research was a cross-sectional study. Risk factors were identified through the questionnaire survey. Office workers were selected based on the proximity of their workstations to the microbiological air sampler used for the mould sampling. Results from the current study suggests that individual susceptibility of exposed subjects might be influenced by several factors associated with mould exposure; for example, inhaled mycotoxins or volatile organic compounds, which may, in some complex way, affect the immune response. This study provides the much needed preliminary baseline data for developing guidelines with validated findings that will be of use for policy decisions in Malaysia regarding indoor air quality. Results from this study are recommended for use in planning and implementing control measures in order to reduce the exposure to indoor mould and promote healthy working environment among the workers.

Characterization of knitted polymeric scaffolds for potential use in ligament tissue engineering.

Different scaffolds have been designed for ligament tissue engineering. Knitted scaffolds of poly-L-lactic acid (PLLA) yarns and co-polymeric yarns of PLLA and poly(glycolic acid) (PLGA) were characterized in the current study. The knitted scaffolds were immersed in medium for 20 weeks, before mass loss, molecular weight, pH value change in medium were tested; changes in mechanical properties were evaluated at different time points. Results showed that the knitted scaffolds had 44% porosity. There was no significant pH value change during degradation, while there was obvious mass loss at initial 4 week, as well as smooth molecular weight drop of PLLA. PLGA degraded more quickly, while PLLA kept its integrity for at least 20 weeks. Young's modulus increased while tensile strength and strain at break decreased with degradation time; however, all of them could maintain the basic requirements for ACL reconstruction. It showed that the knitted polymeric structures could serve as potential scaffolds for tissue-engineered ligaments.

Measurement of the visual contribution to postural steadiness from the COP movement: methodology and reliability.

We studied the reliability of different measures of the visual contribution to postural steadiness by recording the postural sway during standing with eyes open (EO) or eyes closed (EC). The COP trajectory was recorded in 21 subjects aged 42-61 standing on a firm or foam support. The improvement of postural steadiness due to vision was measured with a higher reliability (i.e. lower intra- and inter-subject variabilities) with the sway velocity V, than with the position RMS. Due to the increase of the variability of V and RMS with their own mean values, we quantified the visual contribution to posture by the stabilization ratio (SR), based on a logarithm transform of V or RMS. As compared to the Romberg quotient (EC/EO), SR improved the reliability of the measurement of the visual contribution to posture within individuals, across subjects, and even across different studies in the literature. Our method led to decrease the inter-subject coefficient of variation of this measurement to about 25%, using a foam support. It leads to a similar accuracy in binocular and monocular vision, and it also applies to the quantification of other non-visual sensory contributions to posture.

Development of an integrated CAD-FEA process for below-knee prosthetic sockets.

BACKGROUND: Computer-aided design and manufacturing has been successfully used in prosthetic applications since 1980s. It simplifies the socket rectification process and improves reproducibility but does not introduce any new principle into socket design. Integrating finite element analysis to CAD will provide a more objective assessment of socket fit and improve the chance of a successful first fitting. METHODS: Current study aims to establish a finite element model generation technique directly from geometrical information of commercial prosthetic CAD workstation. A program developed in-house automatically performs meshing of the stump geometry and assigns suitable material properties, load and boundary conditions to the model. The model was validated by comparing predicted pressure with experimentally measured values for one amputee subject. FINDINGS: The predicted pressure distribution has an root-mean-square error of 8.8 kPa compared to experimental values at 10%, 25% and 50% of the gait cycle. INTERPRETATION: Current method was able to develop a finite element model to predict interface pressure reasonably well and can be integrated with prosthetic CAD system to provide quantitative feedback to the prosthetist in an automated process.

Mesenchymal stem cells in musculoskeletal tissue engineering: a review of recent advances in National University of Singapore.

A key factor in the tissue engineering approach to tissue repair and regeneration is the use of appropriate cells. Mesenchymal stem cells (MSCs) are derived from bone marrow stroma or connective tissues and they have the potential to differentiate into various mesenchymal cell lines in vitro and in vivo. These cells hold great promise for musculoskeletal tissue engineering. This review is based mainly on the work which has been done in the National University of Singapore on the use of MSCs for engineering cartilage, growth plate, bone and tendon/ligament as well as the clinical trail of autologous chondrocyte implantation. It can help to shape future research on musculoskeletal tissue engineering.

Internal model approach for gait modeling and classification.

In this paper, we present a novel approach to model and classify gait patterns based on internal models. An internal model consists of two sets of differential equations and a neural network in between. It can effectively describe dynamic movement primitives (DMP), hence is able to model the temporal-spatial gait patterns. An interesting feature of the internal model is, the nonlinear map generated by the neural network can also serve the purpose for gait pattern classification. In this work we use a single hidden layer feedforward network (SLFN), and show that the characteristics of gait patterns can be captured via the output layer weights. The experiment results based on EMGs of gait patterns at five different walking speeds are used to validate the internal model approach.