Quantitative Functional Outcomes Research Articles

Functional Outcomes of Patients Who Underwent Anorectal Malformation Repair Using MRI Guidance

BackgroundDespite the initiation of minimally invasive laparoscopic techniques, the majority of patients who undergo anorectal malformation repair still experience functional bowel issues in childhood, including constipation and fecal incontinence. In this study, we evaluate the functional outcomes of a procedure in which magnetic resonance imaging guidance is used during initial laparoscopic repair to better locate the epicenter of the sphincter muscle complex and pelvic floor with the goal of more accurate placement of the neoanus and improved functional outcomes. MethodsA retrospective chart review evaluated demographic, operative, and outcome details for patients who underwent this procedure. A telephone survey was employed to determine levels of social continence using the validated Baylor Continence Scale and to determine what type of bowel management is used. ResultsTwenty-six patients were included. Median age at operation was 7 months, and median age at follow-up was 4 years old, with a range of 1–9. Bowel management regimen results revealed that 19 % (n = 5) use no bowel management regimen, 58 % (n = 15) use laxatives only, and 23 % (n = 6) use enemas. Enema use was not associated with different spine or sacral anomalies (p = 0.77). Fifteen patients (58 %) answered the Baylor Continence Scale questions and had a median score of 14. No difference was found in scores when accounting for lesion level (p = 0.43), quality of needle placement (p = 0.46), or quality of sphincter muscles (p = 0.75). ConclusionsUsing MRI guidance in the repair of anorectal malformations shows promise in both the qualitative and quantitative functional outcomes of this complex patient population. Level of EvidenceLevel III.

Functional Outcome of Dual Reinnervation with Cross-Facial Nerve Graft and Masseteric Nerve Transfer for Facial Paralysis.

The combination of cross-facial nerve graft (CFNG) and masseteric nerve transfer (MNT) for reinnervation of facial paralysis may provide advantages of both neural sources. However, quantitative functional outcome reports with a larger number of patients are lacking in the literature. Here, the authors describe their 8-year experience with this surgical technique. Twenty patients who presented with complete facial paralysis (duration, <12 months) received dual reinnervation with CFNG and MNT. The functional outcome of the procedure was evaluated with the physician-graded outcome metric eFACE scale. The objective artificial intelligence-driven software Emotrics and FaceReader were used for oral commissure measurements and emotional expression assessment, respectively. The mean follow-up was 31.75 ± 23.32 months. In the eFACE score, the nasolabial fold depth and oral commissure at rest improved significantly ( P < 0.05) toward a more balanced state after surgery. Postoperatively, there was a significant decrease in oral commissure asymmetry while smiling (from 19.22 ± 6.1 mm to 12.19 ± 7.52 mm). For emotional expression, the median intensity score of happiness, as measured by the FaceReader software, increased significantly while smiling (0.28; interquartile range, 0.13 to 0.64). In five patients (25%), a secondary static midface suspension with fascia lata strip had to be performed because of unsatisfactory resting symmetry. Older patients and patients with greater preoperative resting asymmetry were more likely to receive static midface suspension. The authors' results suggest that the combination of MNT and CFNG for reinnervation of facial paralysis provides good voluntary motion and may lessen the use of static midface suspension in the majority of patients. Therapeutic, IV.

Impact of Etiology on Seizure and Quantitative Functional Outcomes in Children with Cerebral Palsy and Medically Intractable Epilepsy Undergoing Hemispherotomy/Hemispherectomy

To compare functional and seizure outcomes in children with vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy following functional hemispherotomy or anatomic hemispherectomy. Consecutive patients satisfying inclusion criteria from 07/01/2015 to 12/01/2019 were reviewed for demographic data and seizure (Engel classification) and functional (Functional Independence Measure for Children) outcomes. After a mean follow-up of 2years 8months (1year 2months), 11 of 18 patients achieved post-operative seizure freedom without significant difference between vascular (5/7) and dysplastic (6/11) etiologies (P= 0.64). Functional assessments were completed for 15 of 18 of subjects, split comparably between groups. Mean change in the Functional Independence Measure for Children from pre-operative baseline to inpatient rehabilitation admission (vascular,-35.3 [13.2]; malformation of cortical development{MCD},-34.5 [25.0]; P= 0.69), inpatient rehabilitation admission to discharge (vascular, 18.7 [9.0]; MCD, 20.8 [11.4]; P= 0.60), and pre-operative evaluation to clinic follow-up (vascular,-7.6 [9.7]; MCD,-3.6 [19.3]; P= 0.61) did not differ between groups. Quantitative functional and seizure outcomes following functional hemispherotomy or anatomic hemispherectomy did not differ significantly between vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy in this study. Hemispheric surgery resulted in minor functional declines from baseline following comprehensive multidisciplinary therapy.

The Impact of Dorsal Root Ganglion Stimulation on Pain Levels and Functionality in Patients With Chronic Postsurgical Knee Pain

BackgroundChronic postsurgical pain is a considerable source of disabling neuropathic pain. Rates of knee replacement surgeries are increasing, and many patients report chronic postsurgical pain in their wake. When conventional therapies prove ineffective, neuromodulation options such as dorsal root ganglion stimulation (DRGS) may be used. However, little is known about the effect of DRGS on improvements in quantitative functional outcome parameters. Materials and MethodsIn a prospective observational study at two pain centers, patients with chronic postsurgical knee pain underwent implantation with a DRGS system after an interdisciplinary multimodal pain program. Ratings of pain, mood, quality of life, and function were captured at baseline and through 12 months of treatment. Quantitative measures (range of motion, walking distance, and pain medication usage) were also recorded. ResultsVisual analog scale ratings of pain decreased from 8.6 to 3.0 (p < 0.0001; N = 11), and other pain measures agreed. Quality of life on the 36-Item Short Form Health Survey questionnaire improved from 69.3 to 87.6 (p < 0.0001), whereas the improvement in depression ratings was nonsignificant. International Knee Documentation Committee questionnaire ratings of function improved from 27.7 to 51.7 (p < 0.0001), which aligned with other functional measures. On average, knee range of motion improved by 24.5°, and walking distance dramatically increased from 125 meters to 1481. Cessation of opioids, antidepressants, and/or anticonvulsants was achieved by 73% of participants. ConclusionsBoth subjective-based questionnaire and quantitative examination-based variables were in broad agreement on the value of DRGS in improving functionality and chronic postsurgical pain in the knee. Although this finding is limited by the small sample size, this intervention may have utility in the many cases in which pain becomes problematic after orthopedic knee surgery.

Abstract 14: Large Gap Peripheral Nerve Repair in a Non-Human Primate Model: Improving Outcomes Utilizing Photochemical Tissue Bonding (PTB) with Acellular Nerve Allograft (ANA)

PURPOSE: Segmental peripheral nerve deficits are challenging injuries associated with poor outcomes. While these injuries afflict civilians (e.g. Boston Marathon Bombing), they have become increasingly prevalent in combat trauma since the advent of improvised explosive devices. Standard of care large-gap (>3cm) reconstruction requires nerve autograft. Alternatives are sought in clinical scenarios where donor limb is not available (e.g. multiple extremity trauma) or donor site morbidity (e.g. painful neuroma formation, loss of function) makes autograft use suboptimal. A variety of alternatives have been proposed including allografts and conduits. Photochemical tissue bonding (PTB) as an alternative to traditional suture neurorrhaphy has been extensively studied in the rodent sciatic nerve model. PTB carries several advantages: reduction of needle trauma, prevention of axonal escape, and a water-tight seal to contain neuroregenerative factors and exclude inflammatory invasion. We report a non-human primate study which recapitulates human anatomy, allows for objective quantitative functional outcomes testing, electrophysiology and histomorphometry. The purpose of this study is to evaluate whether PTB can elevate the performance of acellular nerve allograft (ANA) to that of standard of care autograft/suture. METHODS: Nineteen rhesus macaques underwent 4cm proximal radial nerve defect creation in the right upper extremity, the radial nerve transected proximally at the humeral spiral groove, distally prior to the branch to brachioradialis. The radial nerve was selected as it is responsible for an isolated function with no input from other nerves. Three repair techniques were evaluated: n=6 autograft/suture, n=6 ANA/suture, n=7 ANA photosealed in place with light-activated human amnion wraps (PTB). An objective functional outcome test was conceived using an apparatus that accurately measured the degree of wrist extension as a function of time after surgery. Electromyography (EMG) was performed at 0, 120, 240, and 365 days (euthanasia). Histomorphometry and muscle mass retention were analyzed at euthanasia. RESULTS: Average loss of wrist extension was 88.3 ± 8.2° after radial nerve defect creation. Autograft group animals recovered 82.0° of extension by 7 months. Wrist extension recovery was modestly slower, as expected, in the ANA groups, however, by 8 months the ANA/PTB group recovered 63.0° of extension with no difference in recovery of baseline EMG amplitude as compared to controls (Avance/PTB=75.81% vs. autograft/suture=65.06%). If recovery follows current trajectory, we expect ANA/PTB to demonstrate equivalent outcomes to the autograft/suture group at one year. CONCLUSION: This radial nerve defect model improves upon existing animal models by allowing for large nerve gap testing in a primate model more analogous to the clinical large nerve gap injury in humans. ANA/PTB group functional recovery lagged modestly behind autograft/suture (by as long as 8 weeks) but is approaching equivalence at 8 months. EMG recovery is similar at 8 months. This preliminary data confirms PTB as a promising technique to improve outcomes of large nerve gap reconstruction in combination with autograft (previously demonstrated) and with acellular nerve allograft.

Machine learning methods enable predictive modeling of antibody feature:function relationships in RV144 vaccinees.

The adaptive immune response to vaccination or infection can lead to the production of specific antibodies to neutralize the pathogen or recruit innate immune effector cells for help. The non-neutralizing role of antibodies in stimulating effector cell responses may have been a key mechanism of the protection observed in the RV144 HIV vaccine trial. In an extensive investigation of a rich set of data collected from RV144 vaccine recipients, we here employ machine learning methods to identify and model associations between antibody features (IgG subclass and antigen specificity) and effector function activities (antibody dependent cellular phagocytosis, cellular cytotoxicity, and cytokine release). We demonstrate via cross-validation that classification and regression approaches can effectively use the antibody features to robustly predict qualitative and quantitative functional outcomes. This integration of antibody feature and function data within a machine learning framework provides a new, objective approach to discovering and assessing multivariate immune correlates.

Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris

Severe injuries to the extremities often result in muscle trauma and, in some cases, significant volumetric muscle loss (VML). These injuries continue to be challenging to treat, with few available clinical options, a high rate of complications, and often persistent loss of limb function. To facilitate the testing of regenerative strategies for skeletal muscle, we developed a novel quadriceps VML model in the rat, specifically addressing functional recovery of the limb. Our outcome measures included muscle contractility measurements to assess muscle function and gait analysis for evaluation of overall limb function. We also investigated treatment with muscle autografts, whole or minced, to promote regeneration of the defect area. Our defect model resulted in a loss of muscle function, with injured legs generating less than 55% of muscle strength from the contralateral uninjured control legs, even at 4 weeks post-injury. The autograft treatments did not result in significant recovery of muscle function. Measures of static and dynamic gait were significantly decreased in the untreated, empty defect group, indicating a decrease in limb function. Histological sections of the affected muscles showed extensive fibrosis, suggesting that this scarring of the muscle may be in part the cause of the loss of muscle function in this VML model. Taken together, these data are consistent with clinical findings of reduced muscle function in large VML injuries. This new model with quantitative functional outcome measures offers a platform on which to evaluate treatment strategies designed to regenerate muscle tissue volume and restore limb function.

I25 Intracellular metabolic pathways control immune tolerance

The field that links immunity and metabolism is rapidly expanding. Apparently non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation suggesting that metabolic alterations can be induced by or be consequence of an altered self-immune tolerance. In this context, a key role is played by signalling systems acting as metabolic “sensors” linking energy/nutritional status to regulatory T (Treg) cell functions such s the adipose tissue derived hormone, leptin. We propose that a dynamic/oscillatory activity of intracellular metabolism might represent a shift in understanding the molecular mechanisms governing Treg cell tolerance. In particular, the decision between Treg cell proliferation and hyporesponsiveness arises from their ability to probe the extracellular milieu and, modulating the metabolic intracellular signalling, to determine different qualitative and quantitative functional outcomes.

Regulatory T cells, mTOR kinase, and metabolic activity.

The field that links immunity and metabolism is rapidly expanding. Apparently, non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be a consequence of an altered self-immune tolerance. In this context, a key role is played by signaling systems acting as metabolic "sensors" linking energy/nutritional status to regulatory T (Treg) cell functions. We propose that a dynamic/oscillatory activity of intracellular metabolism, through mTOR modulation, might represent a shift in understanding the molecular mechanisms governing Treg cell tolerance. In particular, the decision between Treg cell proliferation and hyporesponsiveness arises from their ability to probe the extracellular milieu and, modulating the metabolic intracellular signaling, to determine different qualitative and quantitative functional outcomes.

Characterization of a composite injury model of severe lower limb bone and nerve trauma

Severe extremity trauma often results in large zones of injury comprising multiple types of tissue and presents many clinical challenges for reconstruction. Considerable investigation is ongoing in tissue engineering and regenerative medicine therapeutics to improve reconstruction outcomes; however, the vast majority of musculoskeletal trauma models employed for testing the therapeutics consist of single-tissue defects, offering limited utility for investigating strategies for multi-tissue repair. Here we present the first model of composite lower limb bone and nerve injury, characterized by comparison to well-established, single-tissue injury models, using biomaterials-based technologies previously demonstrated to show promise in those models. Quantitative functional outcome measures were incorporated to facilitate assessment of new technologies to promote structural and functional limb salvage following severe extremity trauma. Nerve injury induced significant changes in the morphology and mechanical properties of intact bones. However, BMP-mediated segmental bone regeneration was not significantly impaired by concomitant nerve injury, as evaluated via radiographs, microcomputed tomography (μCT) and biomechanical testing. Neither was nerve regeneration significantly impaired by bone injury when evaluated via histology and electrophysiology. Despite the similar tissue regeneration observed, the composite injury group experienced a marked functional deficit in the operated limb compared to either of the single-tissue injury groups, as determined by quantitative, automated CatWalk gait analysis. As a whole, this study presents a challenging, clinically relevant model of severe extremity trauma to bone and nerve tissue, and emphasizes the need to incorporate quantitative functional outcome measures to benchmark tissue engineering therapies.

Effect of Inspiratory Muscle Training Intensities on Pulmonary Function and Work Capacity in People Who Are Healthy: A Randomized Controlled Trial

Inspiratory muscle training (IMT) has been shown to improve inspiratory muscle function, lung volumes (vital capacity [VC] and total lung capacity [TLC]), work capacity, and power output in people who are healthy; however, no data exist that demonstrate the effect of varying intensities of IMT to produce these outcomes. The purpose of this study was to evaluate the impact of IMT at varying intensities on inspiratory muscle function, VC, TLC, work capacity, and power output in people who are healthy. This was a randomized controlled trial. The study was conducted in a clinical laboratory. Forty people who were healthy (mean age=21.7 years) were randomly assigned to 4 groups of 10 individuals. Three of the groups completed an 8-week program of IMT set at 80%, 60%, and 40% of sustained maximum inspiratory effort. Training was performed 3 days per week, with 24 hours separating training sessions. A control group did not participate in any form of training. Baseline and posttraining measurements of body composition, VC, TLC, inspiratory muscle function (including maximum inspiratory pressure [MIP] and sustained maximum inspiratory pressure [SMIP]), work capacity (minutes of exercise), and power output were obtained. The participants in the 80%, 60%, and 40% training groups demonstrated significant increases in MIP and SMIP, whereas those in the 80% and 60% training groups had increased work capacity and power output. Only the 80% group improved their VC and TLC. The control group demonstrated no change in any outcome measures. This study may have been underpowered to demonstrate improved work capacity and power output in individuals who trained at 40% of sustained maximum inspiratory effort. High-intensity IMT set at 80% of maximal effort resulted in increased MIP and SMIP, lung volumes, work capacity, and power output in individuals who were healthy, whereas IMT at 60% of maximal effort increased work capacity and power output only. Inspiratory muscle training intensities lower than 40% of maximal effort do not translate into quantitative functional outcomes.

Immediate Plate Osteosynthesis of Open Fractures of the Humeral Shaft

The aim of this study was to assess the outcome of immediate plate osteosynthesis in the surgical treatment of open humeral shaft fractures. In a Level I trauma center and teaching hospital, we reviewed 53 patients with open humeral diaphyseal fractures who were treated with immediate open reduction and plate fixation from April 1988 to August 1998. Forty-six patients were available for adequate follow-up and assessment. All fractures were treated with a standard protocol that included irrigation and debridement, intravenous antibiotics, and immediate open reduction and plate fixation. Patients were assessed to determine whether bone grafts were needed during surgery, whether bone union was achieved, the state of the radial nerve, and postoperative complications. No quantitative functional outcomes were assessed, because this was beyond the scope of the study. It was hypothesized that immediate plate osteosynthesis would achieve safe and acceptable clinical results. The 46 patients with adequate final follow-up were assessed at a mean time of 37.5 weeks (13-156 weeks). All fractures united primarily in satisfactory angulation <5 degrees in coronal and sagittal planes. There were 6 delayed unions with a mean time to union of 42.5 weeks (30-72 weeks). The remaining 40 patients united at a mean of 18.4 weeks (12-26 weeks). No patient required subsequent surgery to obtain union of the fracture. Complications were rare, with no deep infections, nonunions, or iatrogenic nerve injuries. Complications included amputation in three patients and dysesthesia in one patient. Two patients had implants removed because of discomfort. Immediate plate osteosynthesis for open humeral shaft fractures has been shown to produce excellent results regarding bone union and absence of deep infections and is a safe technique in the management of these injuries.

An examination of outcome measures to assess functional mobility in childhood survivors of osteosarcoma.

The purpose of this study is to examine outcome measures that assess functional mobility in adolescent survivors of osteosarcoma. We will also identify relationships between functional mobility measurements and specific measure(s) of health-related quality of life (HRQL). Eighteen adolescent survivors of osteosarcoma at least 2 years from surgery at the Children's Hospital of Philadelphia (CHOP) participated in this study. Functional mobility, endurance, perceived exertion, and locomotor efficiency is examined with the following measurement tools: timed up and go (TUG), timed up and down stairs (TUDS), 9-min run-walk, rate of perceived exertion (RPE), and physiological cost index (PCI). The currently used evaluation of function from the American Musculoskeletal Tumor Society (MSTS) is also administered. The Short Form 36 (SF-36) measuring HRQL is used. MSTS scores did not correlate with quantitative functional outcome measures. MSTS scores did not correlate with the HRQL as measured by the SF-36. In contrast, subjects with a higher rate of vitality on the SF-36 walked with more efficiency, farther distance during the 9-min run-walk, and performed the TUDS and TUG with a faster speed. The MSTS does not correlate with actual measures of function or with HRQL. These data demonstrate the need for a new measure to determine functional mobility in survivors of osteosarcoma.

The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force.

Clinical outcome assessment in Multiple Sclerosis (MS) is challenging due to the diversity and fluctuating nature of MS symptoms. Traditional clinical scales such as the EDSS are inadequate in their assessment of key clinical dimensions of MS (e.g. , cognitive function), and they have psychometric limitations as well. Based on analyses of pooled data from natural history studies and from placebo groups in clinical trials, the National MS Society's Clinical Outcomes Assessment Task Force recently proposed a new multidimensional clinical outcome measure, the MS Functional Composite (MSFC). The MSFC comprises quantitative functional measures of three key clinical dimensions of MS: leg function/ambulation, arm/hand function, and cognitive function. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score. Preliminary analyses confirm that: (1) the three clinical dimensions of the MSFC are relatively independent; (2) the MSFC is sensitive to clinical changes over 1- and 2-year intervals; and (3) the MSFC has acceptable criterion validity (i.e., predicts both concurrent and subsequent EDSS change). The advantages and potential limitations of incorporating quantitative functional outcome measures such as the MSFC into collaborative databases are discussed.

The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment

Clinical outcome assessment in Multiple Sclerosis (MS) is challenging due to the diversity and fluctuating nature of MS symptoms. Traditional clinical scales such as the EDSS are inadequate in their assessment of key clinical dimensions of MS (e.g., cognitive function), and they have psychometric limitations as well. Based on analyses of pooled data from natural history studies and from placebo groups in dinical trials, the National MS Society's clinical Outcomes Assessment Task Force recently proposed a new multidimensional clinical outcome measure, the MS Functional Composite (MSFC). The MSFC comprises quantitative functional measures of three key clinical dimensions of MS: leg functionl ambulation, arm/hand function, and cognitive function. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score. Preliminary analyses confirm that: (I) the three clinical dimensions of the MSFC are relatively independent; (2) the MSFC is sensitive to clinical changes over I- and 2-year intervals; and (3) the MSFC has acceptable criterion validity (i.e., predicts both concurrent and subsequent EDSS change). The advantages and potential limitations of incorporating quantitative functional outcome measures such as the MSFC into collaborative databases are discussed.