Dataset Information

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

ABSTRACT:

Objectives

Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps.

Methods

Nine brachial plexus patients with insufficient elbow flexion (i.e., partial denervation) received intramuscular escalating doses of autologous bone marrow-derived mononuclear cells, combined with tendon transfers. Effect parameters included biceps biopsies, motor unit analysis on needle electromyography and computerised muscle tomography, before and after cell therapy.

Results

No adverse effects in vital signs, bone marrow aspiration sites, injection sites, or surgical wound were seen. After cell therapy there was a 52% decrease in muscle fibrosis (p = 0.01), an 80% increase in myofibre diameter (p = 0.007), a 50% increase in satellite cells (p = 0.045) and an 83% increase in capillary-to-myofibre ratio (p < 0.001) was shown. CT analysis demonstrated a 48% decrease in mean muscle density (p = 0.009). Motor unit analysis showed a mean increase of 36% in motor unit amplitude (p = 0.045), 22% increase in duration (p = 0.005) and 29% increase in number of phases (p = 0.002).

Conclusions

Mononuclear cell injection in partly denervated muscle of brachial plexus patients is safe. The results suggest enhanced muscle reinnervation and regeneration. Cite this article: Bone Joint Res 2014;3:38-47.

SUBMITTER: Hogendoorn S

PROVIDER: S-EPMC3942869 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

Hogendoorn S S Duijnisveld B J BJ van Duinen S G SG Stoel B C BC van Dijk J G JG Fibbe W E WE Nelissen R G H H RG

Bone & joint research 20140224 2

<h4>Objectives</h4>Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear ...[more]

PMID: 24565688

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Project description:BackgroundTraumatic brachial plexus injuries (BPIs) disproportionately affect young, able-bodied individuals. Beyond direct costs associated with medical treatment, there are far-reaching indirect costs related to disability and lost productivity. Our objective was to estimate per-patient indirect cost associated with BPI.MethodsWe estimated indirect costs as the sum of (1) short-term wage loss, (2) long-term wage loss, and (3) disability payments. Short-term (6-month) wage loss was the product of missed work days and the average earnings per day. The probability of return to work was derived from a systematic review of the literature, and long-term wage loss and disability payments were estimated. Monte Carlo simulation was used to perform a sensitivity analysis of long-term wage loss by varying age, sex, and return to work simultaneously. Disability benefits were estimated from U.S. Social Security Administration data. All cost estimates are in 2018 U.S. dollars.ResultsA systematic review of the literature demonstrated that the patients with BPI had a mean age of 26.4 years, 90.5% were male, and manual labor was the most represented occupation. On the basis on these demographics, our base case was a 26-year-old American man working as a manual laborer prior to BPI, with an annual wage of $36,590. Monte Carlo simulation estimated a short-term wage loss of $22,740, a long-term wage loss of $737,551, and disability benefits of $353,671. The mean total indirect cost of traumatic BPI in the Monte Carlo simulations was $1,113,962 per patient over the post-injury lifetime (median: $801,723, interquartile range: $22,740 to $2,350,979). If the probability of the patient returning to work at a different, lower-paying job was doubled, the per-patient total indirect cost was $867,987.ConclusionsBPI can have a far-reaching economic impact on both individuals and society. If surgical reconstruction enables patients with a BPI to return to work, the indirect cost of this injury decreases.Level of evidenceEconomic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Project description:Background and purposeBrachial plexus birth injury is caused by traction on the neck during delivery and results in flaccid palsy of an upper extremity commonly involving C5-C6 nerve roots. MR imaging and MR myelography help to assess the anatomic location, extent, and severity of brachial plexus injuries which influence the long-term prognosis along with the surgical decision making. Recently, sonography has been increasingly used as the imaging modality of choice for brachial plexus injuries. The aim of this study was to assess the degree of correlation among brachial plexus sonography, MR imaging, and surgical findings in children with brachial plexus birth injury.Materials and methodsThis prospective study included 55 consecutive patients (girls/boys = 32:23; mean age, 2.1 ± 0.8 months) with brachial plexus birth injury between May 2014 and April 2017. The patients were classified according to the Narakas classification and were followed up at 4- to 6-week intervals for recovery by the Modified Mallet system and sonography without specific preparation for evaluation. All patients had MR imaging under general anesthesia. Nerve root avulsion-retraction, pseudomeningocele, and periscalene soft tissue were accepted brachial plexus injury findings on imaging. Interobserver agreement for MR imaging and the agreement between imaging and surgical findings were estimated using the κ statistic. The diagnostic accuracy of sonography and MR imaging was calculated on the basis of the standard reference, which was the surgical findings.ResultsForty-three patients had pre- and postganglionic injury, 12 had only postganglionic injury findings, and 47% of patients underwent an operation. On sonography, no patients had preganglionic injury, but all patients had postganglionic injury findings. For postganglionic injury, the concordance rates between imaging and the surgical findings ranged from 84% to 100%, and the diagnostic accuracy of sonography and MR imaging was 89% and 100%, respectively. For preganglionic injury, the diagnostic accuracy of MR imaging was 92%. Interobserver agreement and the agreement between imaging and the surgical findings were almost perfect for postganglionic injury (κ = 0.81-1, P < .001).ConclusionsHigh-resolution sonography can identify and locate the postganglionic injury associated with the upper and middle trunks. The ability of sonography to evaluate pre- and the postganglionic injury associated with the lower trunk was quite limited. Sonography can be used as a complement to MR imaging; thus, the duration of the MR imaging examination and the need for sedation can be reduced by sonography.

Project description:The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post-traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow-derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow-derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls.The study was a retrospective cohort design comparing pediatric patients in a phase I clinical trial treated with IV autologous bone marrow-derived mononuclear cells (n = 10) to a control group of age- and severity-matched children (n = 19).The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000 to 2008.Study patients were 5-14 years with postresuscitation Glasgow Coma Scale scores of 5-8.The treatment group received 6 million autologous bone marrow-derived mononuclear cells/kg body weight IV within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our traumatic brain injury management protocol, derived from American Association of Neurological Surgeons guidelines.The primary measure was the Pediatric Intensity Level of Therapy scale used to quantify treatment of elevated intracranial pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction score and days of intracranial pressure monitoring as a surrogate for length of neurointensive care. A repeated-measure mixed model with marginal linear predictions identified a significant reduction in the Pediatric Intensity Level of Therapy score beginning at 24 hours posttreatment through week 1 (p < 0.05). This divergence was also reflected in the Pediatric Logistic Organ Dysfunction score following the first week. The duration of intracranial pressure monitoring was 8.2 ± 1.3 days in the treated group and 15.6 ± 3.5 days (p = 0.03) in the time-matched control group.IV autologous bone marrow-derived mononuclear cell therapy is associated with lower treatment intensity required to manage intracranial pressure, associated severity of organ injury, and duration of neurointensive care following severe traumatic brain injury. This may corroborate preclinical data that autologous bone marrow-derived mononuclear cell therapy attenuates the effects of inflammation in the early post-traumatic brain injury period.

Project description:IntroductionTraumatic brachial plexus injury (TBPI) involves major trauma to the large nerves of the arm which control the movement and sensation. Fifty per cent of injuries result in complete paralysis of the arm with many other individuals having little movement, sensation loss and unremitting pain. The injury often causes severe and permanent disability affecting work and social life, with an estimated cost to the National Health Service and the economy of £35 million per annum. Advances in microsurgery have resulted in an increase in interventions aimed at reconstructing these injuries. However, data to guide evidence-based decisions is lacking. Different outcomes are used across studies to assess the effectiveness of treatments. This has impeded our ability to synthesise results to determine which treatments work best. Studies frequently report short-term clinical outcomes but rarely report longer term outcomes and those focused on quality of life. This project aims to produce a core outcome set (COS) for surgical and conservative management of TBPI. The TBPI COS will contain a minimum set of outcomes to be reported and measured in effectiveness studies and collected through routine clinical care.Methods and analysisThis mixed-methods project will be conducted in two phases. In phase 1 a long list of patient-reported and clinical outcomes will be identified through a systematic review. Interviews will then explore outcomes important to patients. In phase 2, the outcomes identified across the systematic review, and the interviews will be included in a three-round online Delphi exercise aiming to reach consensus on the COS. The Delphi process will include patient and healthcare participants. A consensus meeting will be held to achieve the final COS.Ethics and disseminationThe use of a COS in TBPI will increase the relevance of research and clinical care to all stakeholders, facilitate evidence synthesis and evidence-based decision making. The study has ethical approval.Trial registration numbersCRD42018109843.

Dataset Information

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

Objectives

Methods

Results

Conclusions

Publications

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

Similar Datasets

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