PXL01 alters macrophage response with no effect on axonal outgrowth or Schwann cell response after nerve repair in rats.

Background: Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after repair of the sciatic nerve in healthy Wistar rats. Materials & methods: PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. Results: Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. Conclusion: PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages.

[Box: see text].

Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends.

Introduction: Proteomic analysis of injured human peripheral nerves, particularly focusing on events occurring in the proximal and distal nerve ends, remains relatively underexplored. This study aimed to investigate the molecular patterns underlying a digital nerve injury, focusing on differences in protein expression between the proximal and distal nerve ends. Methods: A total of 26 human injured digital nerve samples (24 men; 2 women; median age 47 [30-66] years), harvested during primary nerve repair within 48 h post-injury from proximal and distal nerve ends, were analyzed using mass spectrometry. Results: A total of 3,914 proteins were identified, with 127 proteins showing significant differences in abundance between the proximal and the distal nerve ends. The downregulation of proteins in the distal nerve end was associated with synaptic transmission, autophagy, neurotransmitter regulation, cell adhesion and migration. Conversely, proteins upregulated in the distal nerve end were implicated in cellular stress response, neuromuscular junction stability and muscle contraction, neuronal excitability and neurotransmitter release, synaptic vesicle recycling and axon guidance and angiogenesis. Discussion: Investigation of proteins, with functional annotations analysis, in proximal and the distal ends of human injured digital nerves, revealed dynamic cellular responses aimed at promoting tissue degeneration and restoration, while suppressing non-essential processes.

Presurgical management of ulnar nerve entrapment in patients with and without diabetes mellitus.

Diabetes mellitus (DM) is a risk factor for the development of ulnar nerve entrapment (UNE). Differences in surgical outcomes for UNE between patients with and without DM have been reported, but studies on presurgical management are scarce. This study aimed to evaluate the presurgical management of UNE in patients with (DM diagnosis < 2 years of UNE diagnosis) and without DM regarding the level of care for diagnosis and the proportion that proceeds to surgery. Data from 6600 patients with UNE between 2004 and 2019 were included from the Skåne Health Care Register (SHR) and cross-linked with data from the Swedish National Diabetes Register (NDR). The group with UNE and DM was compared to the group with UNE without DM and prevalence ratios were calculated using Cox regression analysis. Patients with DM more often got their first UNE diagnosis in secondary care than in primary care (643/667, 96% vs. 5361/5786; 93%). Patients with and without DM, regardless of the type of DM, presence of retinopathy, or HbA1c levels, were surgically treated for UNE to the same extent (258/667, 39% of patients with DM vs. 2131/5786, 37% of patients without DM). The proportion of surgically treated was significantly lower among patients diagnosed with UNE in primary care compared to secondary care (59/449, 13% vs. 2330/5786, 38%). Men were more often surgically treated than women (1228/3191, 38% vs.1161/3262 36%). Patients with UNE and DM are surgically treated to the same extent as patients with UNE but without DM and are more likely to be diagnosed in specialized care.

Acute fingertip and nail injuries in the hand.

A correct diagnosis and treatment of fingertip- and nail injuries, commonly seen in the emergency room, is crucial. Insufficient treatment can result in long-term complications, including finger dysfunction and dysaesthesia, nail deformity, infection, or pain. These remaining problems may induce severe impairment of the quality of life of the patient. This review summarises the diagnosis and treatment.

Experience of living with chronic pain in conjunction with surgery for ulnar nerve entrapment at the elbow-A qualitative study.

PURPOSE: Pain in conjunction with surgery for ulnar nerve entrapment at the elbow is seldom highlighted in the literature. This study aimed to explore patients' experiences of living with chronic pain (≥3 months duration) in conjunction with surgery for ulnar nerve entrapment at the elbow, the consequences and the coping strategies applied. MATERIAL AND METHODS: In-depth interviews were conducted with 10 participants aged 18-60 years. The narratives were analyzed using an inductive approach and content-analysis. RESULTS: The analysis revealed seven main categories: "Physical symptoms/impairments" and "Mood and emotions"comprise symptoms caused by ulnar nerve entrapment at the elbow and chronic pain; "Consequences in daily life" includes challenges and obstacles in every-day life, impact on leisure activities and social life; "Struggling with self-image" embraces experiences closely related to identity; "Coping strategies" covers adaptive resources; "Experience of relief "describes perceived improvements; "Key message for future care" comprises important aspects for healthcare providers to consider. CONCLUSIONS: The results clarify the need for healthcare personnel to adopt a biopsychosocial approach when treating patients with ulnar nerve entrapment at the elbow. Emotional symptoms and sleep disturbances should be identified and treated properly since they contribute to the heavy burden experienced by the individual.

Carpal Tunnel Syndrome and Trigger Finger May Be an Early Symptom of Preclinic Type 2 Diabetes.

Background: Type 2 diabetes (T2D) is a major risk factor for carpal tunnel syndrome (CTS) and trigger finger (TF), but less is known regarding the risk of developing T2D after being diagnosed with CTS or TF. CTS and TF could be early signs of preclinical T2D, and early detection of T2D is crucial to prevent complications and morbidity. Therefore, we investigate the association between CTS/TF and T2D in an adult population without previous T2D using big data registers in Sweden. Methods: Data were collected by crosslinking five nationwide Swedish registers. Individuals aged 40-85 years on December 31, 2010, without prior overt diabetes, were included (n = 3,948,517) and followed up from baseline (ie, a diagnosis of CTS or TF) or January 1, 2011, for controls, until a diagnosis of T2D, prescription of oral antidiabetics or insulin, or end of follow-up four years after baseline. Multivariate Cox regression models were created to calculate hazard ratios for T2D. Results: In total, 37,346 (0.95%) patients were diagnosed with CTS, whereof 1329 (3.46%) developed T2D. There were 17,432 (0.44%) patients who developed TF, whereof 639 (3.67%) developed T2D. Among the controls, 2.73% developed T2D. Compared with controls, there was an increased risk of developing T2D after being diagnosed with either CTS (HR 1.35; 95% confidence interval 1.28-1.43) or TF (HR 1.21; 95% confidence interval 1.12-1.31). Conclusion: Compared with controls, a diagnosis of CTS or TF was associated with 35% and 21% higher risk for later T2D, respectively, which might indicate the existence of undetected T2D in this population.

Risk of hand and forearm conditions due to vibrating hand-held tools exposure: a retrospective cohort study from Sweden.

OBJECTIVES: The occurrence of hand and forearm disorders related to vibration exposure, adjusted for relevant background factors, is scarcely reported. We analysed the prevalence of such conditions in a large population cohort, stratified by sex, and associations with exposure to vibrating hand-held tools. DESIGN: This is a retrospective cohort study. SETTING: Individuals in the Malmö Diet and Cancer Study cohort (MDCS; inclusion 1991-1996; followed until 2018) were asked, 'does your work involve working with vibrating hand-held tools?' (response: 'not at all', 'some' and 'much'). Data were cross-linked with national registers to identify treatment for carpal tunnel syndrome (CTS), ulnar nerve entrapment (UNE), Dupuytren's disease, trigger finger or first carpometacarpal joint (CMC-1) osteoarthritis (OA). Cox regression models, unadjusted and adjusted (age, sex, prevalent diabetes, smoking, hypertension and alcohol consumption), were performed to analyse the effects of reported vibration exposure. PARTICIPANTS: Individuals in the MDCS who had answered the questionnaire on vibration exposure (14 342 out of the originally 30 446 individuals in MDCS) were included in the study. RESULTS: In total, 12 220/14 342 individuals (76%) reported 'no' exposure, 1392/14 342 (9%) 'some' and 730/14 342 (5%) 'much' exposure to vibrating hand-held tools. In men, 'much' exposure was independently associated with CTS (HR 1.71 (95% CI 1.11 to 2.62)) and UNE (HR 2.42 (95% CI 1.15 to 5.07)). 'Some' exposure was independently associated with UNE in men (HR 2.10 (95% CI 1.12 to 3.95)). 'Much' exposure was independently associated with trigger finger in women (HR 2.73 (95% CI 1.49 to 4.99)). We found no effect of vibration exposure on Dupuytren's disease or CMC-1 OA. 'Much' vibration exposure predicted any hand and forearm diagnosis in men (HR 1.44 (95% CI 1.08 to 1.80)), but not in women. CONCLUSIONS: Vibration exposure by hand-held tools increases the risk of developing CTS and UNE and any common hand and forearm conditions in men, whereas women only risk trigger finger and CMC-1 OA. Adjustment for relevant confounders in vibration exposure is crucial.

Surgery for carpal tunnel syndrome in patients with and without diabetes-Is there a difference in the frequency of surgical procedures?

Carpal tunnel syndrome (CTS) occurs more often among individuals with diabetes. The aim of this retrospective observational registry study was to examine whether individuals with diabetes and CTS are treated surgically to the same extent as individuals with CTS but without diabetes. Data on CTS diagnosis and surgery were collected from the Skåne Healthcare Register (SHR). A total of 35,105 individuals (age ≥ 18 years) diagnosed with CTS from 2004-2019 were included. Data were matched to the Swedish National Diabetes Register (NDR. Cox regression models were used to calculate the risk of the use of surgical treatment. Of the 35,105 included individuals with a CTS diagnosis, 17,662 (50%) were treated surgically, and 4,966 (14%) had diabetes. A higher number of individuals with diabetes were treated surgically (2,935/4,966, 59%) than individuals without diabetes (14,727/30,139, 49%). In the Cox regression model, diabetes remained a significant risk factor for surgical treatment (PR 1.14 (95% CI 1.11-1.17)). Individuals with type 1 diabetes were more frequently treated surgically (490/757, 65%) than individuals with type 2 diabetes (2,445/4,209, 58%). There was no difference between the sexes and their treatment. The duration of diabetes was also a risk factor for surgical treatment in diabetes type 2, but high HbA1c levels were not. Individuals with diabetes are more likely to be treated surgically for CTS than individuals without diabetes. Individuals with type 1 diabetes are more likely to be treated surgically for CTS than individuals with type 2 diabetes.

Carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is the most common nerve entrapment disorder worldwide. The epidemiology and risk factors, including family burden, for developing CTS are multi-factorial. Despite much research, its intricate pathophysiological mechanism(s) are not fully understood. An underlying subclinical neuropathy may indicate an increased susceptibility to developing CTS. Although surgery is often performed for CTS, clear international guidelines to indicate when to perform non-surgical or surgical treatment, based on stage and severity of CTS, remain to be elucidated. Neurophysiological examination, using electrophysiology or ultrasonography, performed in certain circumstances, should correlate with the history and findings in clinical examination of the person with CTS. History and clinical examination are particularly relevant globally owing to lack of other equipment. Various instruments are used to assess CTS and treatment outcomes as well as the effect of the disorder on quality of life. The surgical treatment options of CTS - open or endoscopic - offer an effective solution to mitigate functional impairments and pain. However, there are risks of post-operative persistent or recurrent symptoms, requiring meticulous diagnostic re-evaluation before any additional surgery. Health-care professionals should have increased awareness about CTS and all its implications. Future considerations of CTS include use of linked national registries to understand risk factors, explore possible screening methods, and evaluate diagnosis and treatment with a broader perspective beyond surgery, including psychological well-being.

Muscle preservation in proximal nerve injuries: a current update.

Optimal recovery of muscle function after proximal nerve injuries remains a complex and challenging problem. After a nerve injury, alterations in the affected muscles lead to atrophy, and later degeneration and replacement by fat-fibrous tissues. At present, several different strategies for the preservation of skeletal muscle have been reported, including various sets of physical exercises, muscle massage, physical methods (e.g. electrical stimulation, magnetic field and laser stimulation, low-intensity pulsed ultrasound), medicines (e.g. nutrients, natural and chemical agents, anti-inflammatory and antioxidants, hormones, enzymes and enzyme inhibitors), regenerative medicine (e.g. growth factors, stem cells and microbiota) and surgical procedures (e.g. supercharge end-to-side neurotization). The present review will focus on methods that aimed to minimize the damage to muscles after denervation based on our present knowledge.

Round table discussion: the management of idiopathic cubital tunnel syndrome.

Idiopathic cubital tunnel syndrome is the second most common neuropathy in the upper limb. Best evidence regarding the surgical management of this condition has evolved from anterior or submuscular transposition as the former reference standard, to in situ simple release. Differences of opinion remain regarding the timing of surgery, type of surgery and adjunctive surgery. Four surgeons with Level 5 expertise were asked to answer specific questions regarding this condition.

Socioeconomic factors and outcome after repair and reconstruction of digital and major nerve trunk injuries in the upper limb.

Peripheral nerve injuries in the upper limb can lead to substantial disability and pain. We aimed to assess how socioeconomic factors affect outcomes after repaired or reconstructed digital or major nerve trunk injuries in the upper limb. We identified 670 individuals, who underwent surgical nerve repair or reconstruction using sensory nerve autografts, in the Swedish National Quality Registry for Hand Surgery 2010-2018. Socioeconomic factors, including education, cohabitation, type of work, sick leave, immigrant status and income, were gathered from the Swedish statistical agency ( www.scb.se ) and National Diabetes Register (NDR). We calculated prevalence ratios (PR) to assess the relationship between socioeconomic factors and surgical outcomes for the nerve injuries. Individuals with a major nerve trunk injury had higher QuickDASH scores and lower income compared to those with digital nerve injury. Individuals with immigration background (adjusted PR = 2.0, 95% CI 1.2-3.2), history of > 4 weeks of sick leave the year before surgery (adjusted PR = 1.8, 95% CI 1.1-3.1), or education level below tertiary (adjusted PR = 2.8, 95% CI 1.7-4.7) had significantly higher QuickDASH scores. Recognizing impact of non-biological factors, including immigration, prior sick leave, and education level, on outcome after nerve surgery is crucial for improving prognosis in socioeconomically deprived individuals.

The Unpredictable Ulnar Nerve-Ulnar Nerve Entrapment from Anatomical, Pathophysiological, and Biopsychosocial Aspects.

Peripheral nerves consist of delicate structures, including a rich microvascular system, that protect and nourish axons and associated Schwann cells. Nerves are sensitive to internal and external trauma, such as compression and stretching. Ulnar nerve entrapment, the second most prevalent nerve entrapment disorder after carpal tunnel syndrome, appears frequently at the elbow. Although often idiopathic, known risk factors, including obesity, smoking, diabetes, and vibration exposure, occur. It exists in all adult ages (mean age 40-50 years), but seldom affects individuals in their adolescence or younger. The patient population is heterogeneous with great co-morbidity, including other nerve entrapment disorders. Typical early symptoms are paresthesia and numbness in the ulnar fingers, followed by decreased sensory function and muscle weakness. Pre- and postoperative neuropathic pain is relatively common, independent of other symptom severity, with a risk for serious consequences. A multimodal treatment strategy is necessary. Mild to moderate symptoms are usually treated conservatively, while surgery is an option when conservative treatment fails or in severe cases. The decision to perform surgery might be difficult, and the outcome is unpredictable with the risk of complications. There is no consensus on the choice of surgical method, but simple decompression is relatively effective with a lower complication rate than transposition.

Serum biomarkers in patients with hand-arm vibration injury and in controls.

Hand-arm vibration injury is a well-known occupational disorder that affects many workers globally. The diagnosis is based mainly on quantitative psychophysical tests and medical history. Typical manifestations of hand-arm vibration injury entail episodes of finger blanching, Raynaud's phenomenon (RP) and sensorineural symptoms from affected nerve fibres and mechanoreceptors in the skin. Differences in serum levels of 17 different biomarkers between 92 patients with hand-arm vibration injury and 51 controls were analysed. Patients with hand-arm vibration injury entailing RP and sensorineural manifestations showed elevated levels of biomarkers associated with endothelial injury or dysfunction, inflammation, vaso- or neuroprotective compensatory, or apoptotic mechanisms: intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1); thrombomodulin (TM), heat shock protein 27 (HSP27); von Willebrand factor, calcitonin gene-related peptide (CGRP) and caspase-3. This study adds important knowledge on pathophysiological mechanisms that can contribute to the implementation of a more objective method for diagnosis of hand-arm vibration injury.

Diagnostic contribution of multi-frequency vibrometry to detection of peripheral neuropathy in type 1 diabetes mellitus compared with nerve conduction studies.

AIM: The aim was to assess the use of multi-frequency vibrometry (MFV) in detecting diabetic peripheral neuropathy (DPN) in type 1 diabetes in comparison to nerve conduction studies (NCS) and neurothesiometer (NT). Our objectives were to examine how VPTs correlated with NCS parameters, evaluate the efficacy of MFV in distinguishing DPN as well as to investigate whether MFV procedure could be based on fewer frequencies. METHODS: Adults with type 1 diabetes with previous MFV examinations were recruited at Skåne University Hospital in Malmö, Sweden, between 2018 and 2020. Participants were examined regarding nerve function in the lower limbs through MFV, NT and NCS. RESULTS: A total of 66 participants (28 women and 38 men) with a median age of 50 (39 to 64) years were included in the study. Through NCS assessment, 33 participants (50%) were diagnosed with DPN. We found negative correlations between VPTs and all NCS parameters, where the strongest correlation was found between sural nerve amplitude and the 125 Hz frequency of MFV. A combination of four frequencies, two low (4 and 8 Hz) and two high (125 and 250 Hz), showed the highest classification efficacy (AUC 0.83, 95% CI 0.73-0.93). CONCLUSION: We conclude that a strong correlation exists between the sural nerve amplitude and the VPTs at 125 Hz and that VPT testing with MFV can be focused on only four frequencies instead of seven, thus shortening test time, to distinguish DPN in the lower limb.

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 .

Effects of socioeconomic status on patient-reported outcome after surgically treated trigger finger: a retrospective national registry-based study.

OBJECTIVES: To investigate if socioeconomic status impacts patient-reported outcomes after a surgically treated trigger finger (TF). DESIGN AND SETTING: Data on patients with TF treated with surgery were collected from the Swedish National Quality Registry of Hand Surgery (HAKIR) 2010-2019 with an evaluation of symptoms and disability before surgery and at 3 and 12 months after surgery, using the short version of the Disabilities of Arm, Shoulder and Hand (QuickDASH) questionnaire.Data from HAKIR and the Swedish National Diabetes Registry (ndr.nu) were combined with socioeconomic data from Statistics Sweden (scb.sc), analysing the impact of marital status, education level, income, occupation, sickness benefits, days of unemployment, social assistance and migrant status on the outcome by a linear regression model. PARTICIPANTS: In total, 5477 patients were operated on for primary TF during the study period, of whom 21% had diabetes, with a response rate of 35% preoperatively, 26% at 3 months and 25% at 12 months. RESULTS: At all time points, being born in Sweden (preoperatively B-coefficient: -9.74 (95% CI -13.38 to -6.11), 3 months postoperatively -9.80 (95% CI -13.82 to -5.78) and 12 months postoperatively -8.28 (95% CI -12.51 to -4.05); all p<0.001) and high earnings (preoperatively -7.81 (95% CI -11.50 to -4.12), 3 months postoperatively -9.35 (95% CI -13.30 to -5.40) and 12 months postoperatively -10.25 (95% CI -14.37 to -6.13); all p<0.0001) predicted lower QuickDASH scores (ie, fewer symptoms and disability) in the linear regression models. More sick leave during the surgery year predicted higher QuickDASH scores (preoperatively 5.77 (95% CI 3.28 to 8.25; p<0.001), 3 months postoperatively 4.40 (95% CI 1.59 to 7.22; p<0.001) and 12 months postoperatively 4.38 (95% CI 1.35 to 7.40; p=0.005)). No socioeconomic factors impacted the change in QuickDASH score from preoperative to 12 months postoperatively in the fully adjusted model. CONCLUSION: Individuals with low earnings, high sick leave the same year as the surgery and those born outside of Sweden reported more symptoms both before and after surgery, but the relative improvement was not affected by socioeconomic factors.

A self-managed exercise therapy program for wrist osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Post-traumatic wrist osteoarthritis (OA) can eventually lead to pain, muscular weakness, and stiffness of the wrist, which can affect the function of the entire upper limb and reduce the quality of life. Although there is strong evidence that all patients with OA should be offered adequate education and exercises as a first-line treatment, an effective self-management program, including structured education and therapeutic exercises, has not yet been introduced for individuals with wrist OA. This trial aims to evaluate the effectiveness of an exercise therapy program with joint protective strategies to improve neuromuscular control (intervention group) compared to a training program with range of motion exercises (control group). METHODS: This is a single-blinded randomized controlled trial (RCT) with two treatment arms in patients with symptomatic and radiographically confirmed wrist OA. The trial will be conducted at a hand surgery department. The participants will be randomly assigned either to a neuromuscular exercise therapy program or to a training program with range of motion exercises only. Participants in both groups will receive a wrist orthosis and structured education on wrist anatomy, pathophysiology, and joint protective self-management strategies. The programs consist of home exercises that will be performed twice a day for 12 weeks. The Patient-Rated Wrist Evaluation (PRWE) is the primary outcome measure of pain and function. Wrist range of motion (ROM), grip strength, the Numeric Pain Rating scale (NPRS), Disabilities of the Arm, Shoulder, and Hand (DASH), the General Self-Efficacy Scale (GSES), Global Rating of Change (GROC), and conversion to surgery are the secondary measures of outcome. Assessments will be performed at baseline and at 3, 6, and 12 months after baseline by a blinded assessor. DISCUSSION: The upcoming results from this trial may add new knowledge about the effectiveness of a self-managed exercise therapy program on pain and function for individuals with wrist OA. If the present self-management program proves to be effective, it can redefine current treatment strategies and may be implemented in wrist OA treatment protocols. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 27 April 2022. https://clinicaltrials.gov .

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.

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.