Effects of a neuromuscular joint-protective exercise therapy program for treatment of wrist osteoarthritis: a randomized controlled trial.

BACKGROUND: Individuals with wrist osteoarthritis (OA) can suffer from pain, muscular weakness, and impaired motion of the wrist, which can reduce the quality of life. While there is strong evidence that all patients with OA should receive first-line treatment with education and exercises, this approach has not yet been proposed for individuals with wrist OA. Therefore, this trial aimed to evaluate the effectiveness of a first line neuromuscular joint-protective exercise therapy program compared to a training program with range of motion (ROM) exercises in patients with wrist OA. METHODS: In this randomized controlled trial (RCT), 48 patients with symptomatic and radiographically confirmed wrist OA were randomly allocated to a 12-week self-management program with either a neuromuscular joint-protective exercise therapy program (intervention group) or a training program with ROM exercises only (control group). Our primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) with secondary outcome measures of grip strength, range of wrist motion, the Numerical Pain Rating, Scale (NPRS), the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Generalized Self-Efficacy Scale (GSES). The outcome measures were evaluated by a blinded assessor at baseline and 12 weeks. Between-groups differences were analyzed using the Mann-Whitney U test and within-group differences were analyzed with the Wilcoxon signed-rank test. RESULTS: A total of 41 participants were analyzed at 12 weeks. There were no significant differences in PRWE between the groups at 12 weeks (p = 0.27). However, DASH improved significantly in the intervention group compared to the control group (p = 0.02) and NPRS on load within the intervention group (p = 0.006). The difference in DASH should be interpreted with caution since it could be due to a non-significant increase (worsening) from baseline in the control group in combination with a non-significant decrease (improvement) in the intervention group. CONCLUSIONS: This RCT showed that the novel neuromuscular joint-protective exercise therapy program was not superior in reducing pain and improving function compared to a training program with ROM exercises at 12 weeks. Future research is warranted to evaluate the effectiveness of forthcoming exercise therapy treatment programs for patients with wrist OA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 10/05/2022. https://clinicaltrials.gov .

Surgery of Schwannoma in the upper limb - sensitivity and specificity of preoperative magnetic resonance imaging and relation between tumour size and symptoms.

BACKGROUND: Benign peripheral nerve tumours consist of different types, most commonly Schwannomas. Preoperative Magnetic Resonance Imaging (MRI) is commonly performed before surgery and Pathoanatomical Diagnosis (PAD) confirms the diagnosis. Our aims were to study the utility of MRI and the relation between tumour size and symptoms. METHODS: Retrospectively, patients, surgically treated for benign nerve tumours between 2008 and 2019, were identified and preoperative MRI, with measurement of tumour size, PAD, symptoms, peroperative details, and symptomatic outcomes of surgery, were analysed. RESULTS: The sensitivity and specificity to correctly identify Schwannomas with preoperative MRI were 85% and 50%, respectively, based on 30 Schwannomas and nine neurofibromas that were identified. Tumour size did not affect the presence of preoperative symptoms, but patients with sensory dysfunction at last follow-up had larger Schwannomas (p < 0.05). Symptoms as a palpable tumour, paraesthesia and pain improved by surgical excision (p < 0.001, p < 0.001 and p < 0.012, respectively), but sensory and motor dysfunction were common postoperatively. No malignant peripheral nerve sheath tumours (MPNST) were found. Using a surgical microscope, instead of only loop magnification, lowered the risk of perioperative nerve injuries (p < 0.05), but did not further diminish postoperative symptoms. CONCLUSIONS: Early and accurate diagnosis of Schwannomas is valuable for adequate presurgical preparation and prompt surgical intervention. Preoperative examination with MRI has a high sensitivity, but low specificity; although recent advancement in MRI technology indicates improvement in diagnostic precision. Surgical excision is preferably performed early in conjunction with symptomatic debut to improve outcome.

The retinacular ligaments of the digital extensor expansion revisited: An anatomical and biomechanical study.

Our aim was to clarify the anatomy and function of the retinacular ligaments. Forty-eight fingers were dissected and the thickness of the oblique retinacular ligament (ORL) was graded. In four fingers, the motion in the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints was subjected to an in-depth analysis before and after sectioning of either the lateral bands (LB) or the ORLs. The function of the ORLs in restricting flexion of the DIP joint with full extension of the PIP joint was measured in 10 fingers. An ORL could be identified on both sides in all 48 fingers. The distribution of the insertion on the proximal phalanx was 7/96 (7%) in the distal third, 70/96 (73%) in the middle third and 19/96 (20%) in the proximal third. Among the specimens, 29% were graded as having a strong bundle of fibers, 51% as having well-defined and regular fibers and 20% as having thin and sparse fibers. With the PIP joint extended, there was a statistically significant increase in flexion of the DIP joint after the ORL was cut. After the LB was sectioned, the ORL was able to extend the DIP joint with an extension lag of 10-22°. Cutting the ORL did not affect the ability to extend that joint. We conclude that the retinacular ligaments are consistent. Their major role is not connected with finger movement, but to provide stabilizing links between the PIP and DIP joints. They are active in not only specific, uncommon finger positions but also in ordinary use of the fingers.

The Dynamics of Nerve Degeneration and Regeneration in a Healthy Milieu and in Diabetes.

Appropriate animal models, mimicking conditions of both health and disease, are needed to understand not only the biology and the physiology of neurons and other cells under normal conditions but also under stress conditions, like nerve injuries and neuropathy. In such conditions, understanding how genes and different factors are activated through the well-orchestrated programs in neurons and other related cells is crucial. Knowledge about key players associated with nerve regeneration intended for axonal outgrowth, migration of Schwann cells with respect to suitable substrates, invasion of macrophages, appropriate conditioning of extracellular matrix, activation of fibroblasts, formation of endothelial cells and blood vessels, and activation of other players in healthy and diabetic conditions is relevant. Appropriate physical and chemical attractions and repulsions are needed for an optimal and directed regeneration and are investigated in various nerve injury and repair/reconstruction models using healthy and diabetic rat models with relevant blood glucose levels. Understanding dynamic processes constantly occurring in neuropathies, like diabetic neuropathy, with concomitant degeneration and regeneration, requires advanced technology and bioinformatics for an integrated view of the behavior of different cell types based on genomics, transcriptomics, proteomics, and imaging at different visualization levels. Single-cell-transcriptional profile analysis of different cells may reveal any heterogeneity among key players in peripheral nerves in health and disease.

Dose-efficient multimodal microscopy of human tissue at a hard X-ray nanoprobe beamline.

X-ray fluorescence microscopy performed at nanofocusing synchrotron beamlines produces quantitative elemental distribution maps at unprecedented resolution (down to a few tens of nanometres), at the expense of relatively long measuring times and high absorbed doses. In this work, a method was implemented in which fast low-dose in-line holography was used to produce quantitative electron density maps at the mesoscale prior to nanoscale X-ray fluorescence acquisition. These maps ensure more efficient fluorescence scans and the reduction of the total absorbed dose, often relevant for radiation-sensitive (e.g. biological) samples. This multimodal microscopy approach was demonstrated on human sural nerve tissue. The two imaging modes provide complementary information at a comparable resolution, ultimately limited by the focal spot size. The experimental setup presented allows the user to swap between them in a flexible and reproducible fashion, as well as to easily adapt the scanning parameters during an experiment to fine-tune resolution and field of view.

Temporal trend of small nerve fibre degeneration in people with and without type 2 diabetes mellitus.

AIMS: We investigated the long-term temporal trend of intraepidermal nerve fibre density (IENFD) and the association between changes in IENFD and metabolic factors in individuals with and without type 2 diabetes. METHODS: A total of 66 participants were enrolled in this longitudinal population-based study, at baseline consisting of 35 individuals (median 61 years) without diabetes and 31 individuals with type 2 diabetes mellitus. Participants underwent clinical and electrophysiological examinations, as well as a skin biopsy both at baseline and at the follow-up visit (mean 8.1 ± 0.5 years). IENFD was assessed in thin sections of 5 µm, stained with the protein gene product 9.5-antibody and compared between the groups. RESULTS: IENFD decreased during the period in both groups, with a greater decline in the group without diabetes than in type 2 diabetes (-2.3 and -0.6 fibres/mm respectively; p < 0.001). While IENFD at baseline was significantly reduced in type 2 diabetes relative to people without (p < 0.001), no difference in IENFD was found between groups at the follow-up (p = 0.183). Linear mixed model analysis indicated that age, weight and HbA1c were associated with decrease in IENFD in the total population (p < 0.007). IENFD also decreased with increasing age and weight, but not with HbA1c , in the separate groups (p < 0.049). CONCLUSIONS: Despite lower IENFD levels at baseline in type 2 diabetes, IENFD was equal between the groups at follow-up. A decrease in IENFD is to a limited extent affected by body weight, and HbA1c , but age seems to be the long-term determinant of IENFD in an elderly population.

Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb.

BACKGROUND: Traumatic peripheral nerve injury is common and incurs significant cost to individuals and society. Healing following direct nerve repair or repair with autograft is slow and can be incomplete. Several bioengineered nerve wraps or devices have become available as an alternative to direct repair or autologous nerve graft. Nerve wraps attempt to reduce axonal escape across a direct repair site and nerve devices negate the need for a donor site defect, required by an autologous nerve graft. Comparative evidence to guide clinicians in their potential use is lacking. We collated existing evidence to guide the clinical application of currently available nerve wraps and conduits. OBJECTIVES: To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (direct repair or nerve autograft). SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 26 January 2022. We searched online and, where not accessible, contacted societies' secretariats to review abstracts from the British Surgical Society of the Hand, International Federation of Surgical Societies of the Hand, Federation of European Surgical Societies of the Hand, and the American Society for Peripheral Nerve from October 2007 to October 2018. SELECTION CRITERIA: We included parallel group randomised controlled trials (RCTs) and quasi-RCTs of nerve repair in the upper limb using a bioengineered wrap or conduit, with at least 12 months of follow-up. DATA COLLECTION AND ANALYSIS: We used standard Cochrane procedures. Our primary outcomes were 1. muscle strength and 2. sensory recovery at 24 months or more. Our secondary outcomes were 3. British Medical Research Council (BMRC) grading, 4. integrated functional outcome (Rosén Model Instrument (RMI)), 5. touch threshold, 6. two-point discrimination, 7. cold intolerance, 8. impact on daily living measured using the Disability of Arm Shoulder and Hand Patient-Reported Outcome Measure (DASH-PROM), 9. sensory nerve action potential, 10. cost of the device, and 11. adverse events (any and specific serious adverse events (further surgery)). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: Five studies involving 213 participants and 257 nerve injuries reconstructed with wraps or conduits (129 participants) or standard repair (128 participants) met the inclusion criteria. Of those in the standard repair group, 119 nerve injuries were managed with direct epineurial repair, and nine autologous nerve grafts were performed. One study excluded the outcome data for the repair using an autologous nerve graft from their analysis, as it was the only autologous nerve graft in the study, so data were available for 127 standard repairs. There was variation in the functional outcome measures reported and the time postoperatively at which they were recorded. Mean sensory recovery, assessed with BMRC sensory grading (range S0 to S4, higher score considered better) was 0.03 points higher in the device group (range 0.43 lower to 0.49 higher; 1 RCT, 28 participants; very low-certainty evidence) than in the standard repair group (mean 2.75 points), which suggested little or no difference between the groups, but the evidence is very uncertain. There may be little or no difference at 24 months in mean touch thresholds between standard repair (0.81) and repair using devices, which was 0.01 higher but this evidence is also very uncertain (95% confidence interval (CI) 0.06 lower to 0.08 higher; 1 trial, 32 participants; very low-certainty evidence). Data were not available to assess BMRC motor grading at 24 months or more. Repair using bioengineered devices may not improve integrated functional outcome scores at 24 months more than standard techniques, as assessed by the Rosén Model Instrument (RMI; range 0 to 3, higher scores better); the CIs allow for both no important difference and a better outcome with standard repair (mean RMI 1.875), compared to the device group (0.17 lower, 95% CI 0.38 lower to 0.05 higher; P = 0.13; 2 trials, 60 participants; low-certainty evidence). Data from one study suggested that the five-year postoperative outcome of RMI may be slightly improved after repair using a device (mean difference (MD) 0.23, 95% CI 0.07 to 0.38; 1 trial, 28 participants; low-certainty evidence). No studies measured impact on daily living using DASH-PROM. The proportion of people with adverse events may be greater with nerve wraps or conduits than with standard techniques, but the evidence is very uncertain (risk ratio (RR) 7.15, 95% CI 1.74 to 29.42; 5 RCTs, 213 participants; very low-certainty evidence). This corresponds to 10 adverse events per 1000 people in the standard repair group and 68 per 1000 (95% CI 17 to 280) in the device group. The use of nerve repair devices may be associated with a greater need for revision surgery but this evidence is also very uncertain (12/129 device repairs required revision surgery (removal) versus 0/127 standard repairs; RR 7.61, 95% CI 1.48 to 39.02; 5 RCTs, 256 nerve repairs; very low-certainty evidence). AUTHORS' CONCLUSIONS: Based on the available evidence, this review does not support use of currently available nerve repair devices over standard repair. There is significant heterogeneity in participants, injury pattern, repair timing, and outcome measures and their timing across studies of nerve repair using bioengineered devices, which make comparisons unreliable. Studies were generally small and at high or unclear risk of bias. These factors render the overall certainty of evidence for any outcome low or very low. The data reviewed here provide some evidence that more people may experience adverse events with use of currently available bioengineered devices than with standard repair techniques, and the need for revision surgery may also be greater. The evidence for sensory recovery is very uncertain and there are no data for muscle strength at 24 months (our primary outcome measures). We need further trials, adhering to a minimum standard of outcome reporting (with at least 12 months' follow-up, including integrated sensorimotor evaluation and patient-reported outcomes) to provide high-certainty evidence and facilitate more detailed analysis of effectiveness of emerging, increasingly sophisticated, bioengineered repair devices.

Vibrotactile sense might improve over time in paediatric subjects with type 1 diabetes-A mid-term follow-up using multifrequency vibrometry.

AIM: Impaired vibrotactile sense, mirroring diabetic peripheral neuropathy, is present among children and adolescents with type 1 diabetes. This study aims to re-examine the vibrotactile sense of paediatric type 1 diabetes subjects in order to evaluate any alterations in the vibrotactile sense over time. METHODS: A VibroSense Meter I device was used to determine the vibrotactile perception thresholds (VPTs) for seven frequencies from the pulp of index and little fingers and for five frequencies from metatarsal heads one and five on the sole of the foot, of 37 children and adolescents with type 1 diabetes, previously examined in a larger cohort. Subjects were followed up after a median time of 30 months. Z-scores of VPTs were calculated using previously collected normative data. RESULTS: Vibrotactile perception thresholds improved over time at low frequencies (especially 16 Hz) on the foot, while not being statistically significant different on the rest of the frequencies, either on hand or foot. VPTs were not correlated with HbA1c. CONCLUSION: A mid-term follow-up of vibrotactile sense in paediatric subjects with type 1 diabetes shows a conceivable normalization of previously impaired vibrotactile sense on some frequencies on the foot, indicating that vibrotactile sense might fluctuate over time.

Psychometric properties of patient-reported outcome measures (PROMs) in wrist osteoarthritis: test-retest reliability and construct validity.

BACKGROUND: Patient-reported outcome measures (PROMs) are frequently used to assess the effects of treatments in patients with wrist osteoarthritis (OA), but their psychometric properties have not been evaluated in this group of patients. Our aim was to evaluate the psychometric properties of the Numeric Rating Scale (NRS pain at rest, pain on motion without load, and pain on load), the Disabilities of the Arm, Shoulder and Hand (DASH) and the Patient Rated Wrist Evaluation (PRWE) questionnaires in patients with wrist OA regarding test-retest reliability and construct validity. METHODS: The NRS, DASH and PRWE were self-administered by 50 patients (40 men and 10 women, mean age 66 years) in a postal survey on two occasions, two weeks apart. Test-retest reliability was evaluated by Kappa statistics and the Spearman rank correlation coefficients (rho) were calculated to evaluate construct validity. RESULTS: The Kappa coefficients for DASH, PRWE and NRS pain on motion without load and NRS pain on load were > 0.90, 95% CI ranging from 0.84 to 0.98, while NRS pain at rest was 0.83, 95% CI 0.73-0.92. The construct validity of the PROMs was confirmed by three formulated hypotheses: a higher correlation between PRWE and NRS (rho 0.80-0.91, p < 0.001) was found, compared to DASH and NRS (rho 0.68-0.80, p < 0.001); the NRS pain on motion without load and NRS pain on load correlated more strongly to PRWE and DASH (rho 0.71-0.91, p < 0.001) compared to NRS pain at rest (rho 0.68-0.80) and a high correlation between PRWE and DASH was found (rho 0.86, p < 0.001). CONCLUSIONS: The NRS, DASH and PRWE demonstrate excellent test-retest reliability and moderate to high construct validity in patients with wrist OA. These PROMs are highly related, but they also differ. Therefore, they complement each other in ensuring a comprehensive evaluation of perceived disability in wrist OA. As PRWE showed the highest test-retest reliability and the highest relation to the other PROMs, the sole use of the PRWE can be recommended in clinical practice.

Vibrotactile sense 5 years after carpal tunnel release in people with diabetes: A prospective study with matched controls.

AIM: To compare vibrotactile sense, 5 years after carpal tunnel release in people with and without diabetes. METHODS: Out of 35 people with diabetes and carpal tunnel syndrome, age- and gender-matched with 31 people without diabetes but with idiopathic carpal tunnel syndrome, 27 and 30 people, respectively, participated in this prolonged follow-up. Vibration perception threshold of the index and little finger (median and ulnar nerve, respectively), 5 years after surgery, was measured at seven different frequencies (8, 16, 32, 64, 125, 250 and 500 Hz). RESULTS: Significant improvement of vibration perception threshold from 1 to 5 years after carpal tunnel release was found at 64 Hz for people with diabetes, while improvement for people without diabetes was demonstrated at several frequencies (64-250 Hz). However, both groups demonstrated a significant decrease in vibration perception threshold for the low frequencies (8-16 Hz). At 5 years, people with diabetes had significantly impaired vibration perception threshold at the index finger for high frequencies (125-500 Hz), and for nearly all frequencies (16 Hz, 64-500 Hz) at the little finger, compared to people without diabetes. CONCLUSION: After carpal tunnel release, significant mid-term improvement of vibrotactile sense appears limited for people with diabetes, compared to a continuous improvement for people without diabetes. In addition, a decline in low-frequency vibrotactile sense occurs for the median as well as the ulnar nerve innervated fingers. Clinical Trial Registration NCT01201109.

Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes.

AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes. The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN. METHODS: A quantitative mass spectrometry-based proteomics analysis was made of peripheral nerves from age- and gender-matched living human male tissue donors; nine type 2 diabetes subjects, with decreased sural nerve action potentials indicating DPN, and six controls without type 2 diabetes, with normal electrophysiology results. RESULTS: A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between type 2 diabetes and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins was made to find clusters of similar proteins in type 2 diabetes subjects and healthy controls. CONCLUSIONS: This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without type 2 diabetes, which may aid in finding biomarkers of importance to DPN development.

3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects.

BACKGROUND: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. MATERIAL AND METHODS: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. RESULTS: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. CONCLUSIONS: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.

Gold and Cobalt Oxide Nanoparticles Modified Poly-Propylene Poly-Ethylene Glycol Membranes in Poly (ε-Caprolactone) Conduits Enhance Nerve Regeneration in the Sciatic Nerve of Healthy Rats.

Reconstruction of nerve defects is a clinical challenge. Autologous nerve grafts as the gold standard treatment may result in an incomplete restoration of extremity function. Biosynthetic nerve conduits are studied widely, but still have limitations. Here, we reconstructed a 10 mm sciatic nerve defect in healthy rats and analyzed nerve regeneration in poly (ε-caprolactone) (PCL) conduits longitudinally divided by gold (Au) and gold-cobalt oxide (AuCoO) nanoparticles embedded in poly-propylene poly-ethylene glycol (PPEG) membranes (AuPPEG or AuCoOPPEG) and compared it with unmodified PPEG-membrane and hollow PCL conduits. After 21 days, we detected significantly better axonal outgrowth, together with higher numbers of activated Schwann cells (ATF3-labelled) and higher HSP27 expression, in reconstructed sciatic nerve and in corresponding dorsal root ganglia (DRG) in the AuPPEG and AuCoOPPEG groups; whereas the number of apoptotic Schwann cells (cleaved caspase 3-labelled) was significantly lower. Furthermore, numbers of activated and apoptotic Schwann cells in the regenerative matrix correlated with axonal outgrowth, whereas HSP27 expression in the regenerative matrix and in DRGs did not show any correlation with axonal outgrowth. We conclude that gold and cobalt-oxide nanoparticle modified membranes in conduits improve axonal outgrowth and increase the regenerative performance of conduits after nerve reconstruction.

Injury-Induced HSP27 Expression in Peripheral Nervous Tissue Is Not Associated with Any Alteration in Axonal Outgrowth after Immediate or Delayed Nerve Repair.

We investigated injury-induced heat shock protein 27 (HSP27) expression and its association to axonal outgrowth after injury and different nerve repair models in healthy Wistar and diabetic Goto-Kakizaki rats. By immunohistochemistry, expression of HSP27 in sciatic nerves and DRG and axonal outgrowth (neurofilaments) in sciatic nerves were analyzed after no, immediate, and delayed (7-day delay) nerve repairs (7- or 14-day follow-up). An increased HSP27 expression in nerves and in DRG at the uninjured side was associated with diabetes. HSP27 expression in nerves and in DRG increased substantially after the nerve injuries, being higher at the site where axons and Schwann cells interacted. Regression analysis indicated a positive influence of immediate nerve repair compared to an unrepaired injury, but a shortly delayed nerve repair had no impact on axonal outgrowth. Diabetes was associated with a decreased axonal outgrowth. The increased expression of HSP27 in sciatic nerve and DRG did not influence axonal outgrowth. Injured sciatic nerves should appropriately be repaired in healthy and diabetic rats, but a short delay does not influence axonal outgrowth. HSP27 expression in sciatic nerve or DRG, despite an increase after nerve injury with or without a repair, is not associated with any alteration in axonal outgrowth.

Correction to: Gender differences in nerve regeneration after sciatic nerve injury and repair in healthy and in type 2 diabetic Goto-Kakizaki rats.

An amendment to this paper has been published and can be accessed via the original article.

3D analysis of the myenteric plexus of the human bowel by X-ray phase-contrast tomography - a future method?

OBJECTIVES: Light microscopical analysis in two dimensions, combined with immunohistochemistry, is presently the gold standard to describe the enteric nervous system (ENS). Our aim was to assess the usefulness of three-dimensional (3D) imaging by X-ray phase-contrast tomography in evaluating the ENS of the human bowel. MATERIAL AND METHODS: Myenteric ganglia were identified in full-thickness biopsies of the ileum and colon by hematoxylin & eosin staining. A1-mm biopsy punch was taken from the paraffin blocks and placed into a Kapton® tube for subsequent tomographic investigation. The samples were scanned, without further preparation, using phase-contrast tomography at two different scales: overview scans (performed with laboratory setups), which allowed localization of the nervous tissue (∼1µm effective voxel size); and high-resolution scans (performed with a synchrotron endstation), which imaged localized regions of 320x320x320 µm3 (176 nm effective voxel size). RESULTS: The contrast allowed us to follow the shape and the size changes of the ganglia, as well as to study their cellular components together with the cells and cellular projections of the periganglional space. Furthermore, it was possible to show the 3D network of the myenteric plexus and to quantify its volume within the samples. CONCLUSIONS: Phase-contrast X-ray tomography can be applied for volume analyses of the human ENS and to study tissue components in unstained paraffin-embedded tissue biopsies. This technique could potentially be used to study disease mechanisms, and to compare healthy and diseased tissues in clinical research.

Cold intolerance and neuropathic pain after peripheral nerve injury in upper extremity.

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re-education. In a cross-sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow-up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re-education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire-Italian version (CISS-it, cut-off pathology >30/100 points), CISS questionnaire-12 item version (CISS-12, 0-46 points-grouping: healthy that means no cold intolerance [0-14], mild [15-24], moderate [25-34], severe [35-42], very severe [43-46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique-4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two-point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC-scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS-it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain.

Evaluation of small nerve fiber dysfunction in type 2 diabetes.

OBJECTIVES: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. MATERIALS AND METHODS: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). RESULTS: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = -.268, P = .013) and Total Neuropathy Score (r = -.219, P = .042). Positive correlations were found between IENFD and sural nerve amplitude (r = .371, P = .001) as well as conduction velocity of both the sural (r = .241, P = .029) and peroneal nerve (r = .258, P = .018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). CONCLUSIONS: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.

Social participation in persons with upper limb amputation receiving an esthetic prosthesis.

STUDY DESIGN: Qualitative study. INTRODUCTION: An amputation injury to the hand may lead to not only impaired hand function but also psychosocial consequences. PURPOSE OF THE STUDY: The purpose of the study was to explore personal experiences of social participation for persons provided with an esthetic prosthesis after acquired upper limb amputation. METHODS: Thirteen persons with acquired upper limb amputation, who were in need of and had received an esthetic prosthesis, were interviewed. The transcribed text was subjected to content analysis. RESULTS: The emotional reactions to a visibly different hand were linked to a changed appearance and a feeling of being exposed. Recollecting the accident could result in nightmares and sleeping disorders. A change of personality, due to sadness after the amputation was expressed, as well as social insecurity and impact on relations and life roles. Adapting to social challenges comprised hiding or exposing the hand, using personal internal resources and receiving support from others. The esthetic prosthesis contributed to an intact appearance and could serve as a facilitator for initial or long-term social participation. The time that had passed since the injury made it easier to deal with the consequences or in achieving acceptance. DISCUSSION: Coping with emotions and social relations after an acquired amputation can be difficult and complex. CONCLUSIONS: Individual needs must be considered and questions about appearance and how it may affect social participation must be asked. An esthetic prosthesis can normalize the appearance and offer the confidence needed to facilitate social participation in those struggling with appearance-related concerns.

Patient-reported quality of life and hand disability in elderly patients after a traumatic hand injury - a retrospective study.

BACKGROUND: Hand injuries occur at any age and cause disability in hand and arm function as well as impaired quality of life, but no study has focused on hand disability and quality of life in the elderly after a hand injury. Globally, the population over 60 years of age is expected to double by 2050 and more hand injuries are estimated among the elderly population. Our goal is to obtain more information and a better understanding of problems elderly patients experience after a hand injury to be able in the future to optimally relocate resources in the health care sector with respect to numbers and injury pattern as well as to health status of these patients. METHODS: Patients aged more than 65 years with a traumatic hand/wrist/forearm injury treated (July 1st 2013 - June 30th 2014) at department of Hand Surgery, Malmö, Sweden were included. Health-related outcome questionnaires, i.e. QuickDASH, SF-36, Visual Analogue Scale (VAS), Cold Intolerance Severity Score (CISS), and general information were mailed to the patients (time from injury: > 1.5-2.5 years). The participants were compared in groups according to age, gender, cold intolerance, injury severity and previous occupation. RESULTS: One hundred and thirty-seven participants responded [response rate 55%; non-responders (n = 113); only difference between groups was that non-responders were older]. Women were older than men at the time of injury (p = 0.04) and differed regarding living conditions. The main differences in QuickDASH, all VAS questions, and the majority of SF-36 subscales (p < 0.05) were found in the participants with CISS > 50, who experienced more impairment. More serious injuries (Modified HISS) were found to have higher QuickDASH and CISS score as well as more functional impairment (p < 0.05). Few differences were found in groups divided according to age, gender (although men experiencing less functional impairment in QuickDASH), previous occupation and injured hand. CONCLUSIONS: Patients aged more than 65 years at the time a hand injury was sustained, generally experience a high-level quality of life and limited functional problems after such an injury, but patients with CISS > 50 and with a more serious injury were more severely affected.