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Frontiers in Neurology 2024Although exercise is recommended for cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN), the effective types of exercise for preventing and treating...
PURPOSE
Although exercise is recommended for cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN), the effective types of exercise for preventing and treating CIPN remain unclear. This systematic review and network meta-analysis (NMA) aimed to evaluate the comparative effects of exercise on CIPN.
METHODS
We included relevant randomized controlled trials (RCTs) identified in a 2019 systematic review that evaluated the effects of exercise on CIPN and conducted an additional search for RCTs published until 2023. We evaluated the risk of bias for each RCT; the comparative effectiveness of exercise on patient-reported quality of life (QOL) through an NMA; and the effectiveness of exercise on QOL scores, patient-reported CIPN symptoms, and pain through additional meta-analyses.
RESULTS
Twelve studies (exercise, = 540; control, = 527) comparing 8 exercise interventions were included in the analysis. All studies were determined to have a high risk of bias. The meta-analyses showed significantly improved QOL [standard mean differences (SMD) 0.45; 95% confidence interval (CI) = 0.12 to 0.78] and CIPN symptoms (SMD 0.46; 95% CI = 0.11 to 0.82). No severe adverse events were reported. Pain tended to improve with exercise (SMD 0.84; 95% CI = -0.11 to 1.80). An NMA suggested that the interventions of a combination of balance and strength training showed a significant improvement in QOL scores compared to the control.
CONCLUSION
Exercise interventions may be beneficial for improving QOL and CIPN symptoms. High-quality large clinical trials and data are needed to conclude that exercise is beneficial and safe.
PubMed: 38352137
DOI: 10.3389/fneur.2024.1346099 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
Toxins Sep 2023The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain... (Review)
Review
BACKGROUND
The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain disorders (NP).
METHODS
A comprehensive literature search was conducted using Medline, Web of Science, and the Cochrane Library databases. Only randomized clinical trials (RCT) published between 2003 and the end of June 2023, investigating the use of BTX to treat NP, were selected. PICO guidelines were used to select and tabulate the articles.
RESULTS
A total of 6 RCTs were selected. Five articles used BTX injections to treat classical trigeminal neuralgia, and one to treat post-herpetic neuralgia. A total of 795 patients received BTX injections. The selected studies utilised different doses and methods of injections and doses. All the selected studies concluded superiority of BTX injections over placebo for reducing pain levels, and 5 out 6 of them highlighted an improvement in the patient's quality of life. Most of the studies reported transient and mild side effects.
CONCLUSION
There is evidence of the efficacy of BTX injections in orofacial pain management. However, improved study protocols are required to provide direction for the clinical use of BTX to treat various orofacial neuropathic pain disorders.
Topics: Humans; Botulinum Toxins; Facial Pain; Trigeminal Neuralgia; Databases, Factual; Neuralgia
PubMed: 37755967
DOI: 10.3390/toxins15090541 -
Frontiers in Pharmacology 2023Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of...
Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of life and survivorship in affected patients. Genetic polymorphisms in the CYP3A family have been investigated but the findings have been inconsistent and contradictory. A systematic review identified 12 pharmacogenetic studies investigating genetic variation in and and TIPN. In our candidate gene study, 288 eligible participants (211 taxane participants receiving docetaxel or paclitaxel, and 77 control participants receiving oxaliplatin) were successfully genotyped for and . Genotyping data was transformed into a combined CYP3A metaboliser phenotype: Poor metabolisers, intermediate metabolisers and extensive metabolisers. Individual genotypes and combined CYP3A metaboliser phenotypes were assessed in relation to neurotoxicity, including by meta-analysis where possible. In the systematic review, no significant association was found between and TIPN in seven studies, with one study reporting a protective association. For , one study has reported an association with TIPN, while four other studies failed to show an association. Evaluation of our patient cohort showed that paclitaxel was found to be more neurotoxic than docetaxel ( < 0.001). Diabetes was also significantly associated with the development of TIPN. The candidate gene analysis showed no significant association between either SNP () and the development of TIPN overall, or severe TIPN. Meta-analysis showed no association between these two variants and TIPN. Transformed into combined CYP3A metaboliser phenotypes, 30 taxane recipients were poor metabolisers, 159 were intermediate metabolisers, and 22 were extensive metabolisers. No significant association was observed between metaboliser status and case-control status. We have shown that the risk of peripheral neuropathy during taxane chemotherapy is greater in patients who have diabetes. CYP3A genotype or phenotype was not identified as a risk factor in either the candidate gene analysis or the systematic review/meta-analysis, although we cannot exclude the possibility of a minor contribution, which would require a larger sample size.
PubMed: 37469869
DOI: 10.3389/fphar.2023.1178421 -
Heliyon Mar 2024Many clinical management strategies have been proposed to deal with diabetic foot ulcers. However, the occurrence and recurrence of foot ulcers remain the major problems...
Many clinical management strategies have been proposed to deal with diabetic foot ulcers. However, the occurrence and recurrence of foot ulcers remain the major problems for diabetics. This study aims to identify, visualize, and characterize the meta-analyses on diabetic foot ulcer research. Articles published online were retrieved from the Web of Science core collection database using a search query incorporating MeSH terms and topics related to diabetic foot ulcers and meta-analysis. The publications were then analyzed for basic characteristics, including publication year, countries, topics covered, references, and keywords discussed in the articles. Data visualization was performed using CiteSpace. 334 meta-analyses and systematic reviews on diabetic foot ulcers were identified. The number of publications has experienced rapid growth in recent years (nearly 6-fold since 2016). The United States, China, Netherlands, England, and Australia had a strong collaboration in the contribution of publication. 7 primary topics were summarized from the top 100 highly cited publications: #1 Interventions (proportion: 59%), #2 Risk factors and Prevention (22%), #3 Epidemiology analysis (6%), #4 Cost-effectiveness of interventions (5%), #5 Long-term prognosis (3%), #6 Quality of life analysis (3%), and #7 Economic burden analysis (2%). Footwear and offloading interventions, multidisciplinary care, hyperbaric oxygen, platelet-rich plasma, and negative pressure wound therapies are highly regarded in terms of intervention. Diabetic foot osteomyelitis, peripheral diabetic neuropathy, chronic limb-threatening ischemia, and infections are the main comorbidities. In recent years, offloading interventions, debridement, telemedicine, long-term prognosis, and economic burden analyses have gradually received attention. Individualized treatment, multidisciplinary collaboration, quality of life considerations, and economic burden analyses are the long-term concerns.
PubMed: 38496839
DOI: 10.1016/j.heliyon.2024.e27534 -
Journal of Plastic, Reconstructive &... Sep 2023Peripheral nerve injuries (PNI) are predominantly treated by anatomical repair or reconstruction with autologous nerve grafts or allografts. Motor nerve transfers for... (Review)
Review
BACKGROUND
Peripheral nerve injuries (PNI) are predominantly treated by anatomical repair or reconstruction with autologous nerve grafts or allografts. Motor nerve transfers for PNI in the upper extremity are well established; however, this technique is not yet widely used in the lower extremity. This literature review presents an overview of the current options and postoperative results for nerve transfers as a treatment for nerve injury in the lower extremity.
METHODS
A systematic search in PubMed and Embase databases was performed. Full-text English articles describing surgical procedures and postoperative outcomes of nerve transfers in the lower extremity were included. The primary outcome was postoperative muscle strength measured using the British Medical Research Council (MRC) scale, with MRC> 3 considered good and postoperative return of sensation reported according to the modified Highet classification.
RESULTS
A total of 36 articles for motor nerve transfer and 7 for sensory nerve transfer were included. Sixteen articles described motor nerve transfers for treating peroneal nerve injury, 17 for femoral nerve injury, 2 for tibial nerve injury, and one for obturator nerve injury. Transfers of multiple branches to restore deep peroneal nerve function led to a good outcome in 58% of patients and 43% when a single branch was used as a donor. The transfer of multiple branches for femoral nerve or obturator nerve repair was performed in all reported patients with a good outcome.
CONCLUSIONS
The transfer of motor nerves for the recovery of PNI is a feasible technique with relatively low risks and great benefits. The correct indication, timing, and surgical technique are essential for optimizing results.
Topics: Humans; Nerve Transfer; Neurosurgical Procedures; Lower Extremity; Peripheral Nerve Injuries; Peroneal Neuropathies; Leg Injuries
PubMed: 37390541
DOI: 10.1016/j.bjps.2023.06.011 -
Frontiers in Neurology 2023The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD...
BACKGROUND/OBJECTIVES
The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD in adults is difficult, because phenotypes are different from those in children and influenced by symptoms from acquired conditions. This systematic literature review aims to answer the following questions: (1) What is the diagnostic yield of exome/genome sequencing (ES/GS) for IMD in adults with unsolved phenotypes? (2) What characteristics do adult patients diagnosed with IMD through ES/GS have?
METHODS
A systematic search was conducted using the following search terms (simplified): "Whole exome sequencing (WES)," "Whole genome sequencing (WGS)," "IMD," "diagnostics" and the 1,450 known metabolic genes derived from ICIMD. Data from 695 articles, including 27,702 patients, were analyzed using two different methods. First, the diagnostic yield for IMD in patients presenting with a similar phenotype was calculated. Secondly, the characteristics of patients diagnosed with IMD through ES/GS in adulthood were established.
RESULTS
The diagnostic yield of ES and/or GS for adult patients presenting with unexplained neurological symptoms is 11% and for those presenting with dyslipidemia, diabetes, auditory and cardiovascular symptoms 10, 9, 8 and 7%, respectively. IMD patients diagnosed in adulthood (n = 1,426), most frequently portray neurological symptoms (65%), specifically extrapyramidal/cerebellar symptoms (57%), intellectual disability/dementia/psychiatric symptoms (41%), pyramidal tract symptoms/myelopathy (37%), peripheral neuropathy (18%), and epileptic seizures (16%). The second most frequently observed symptoms were ophthalmological (21%). In 47% of the IMD diagnosed patients, symptoms from multiple organ systems were reported. On average, adult patients are diagnosed 15 years after first presenting symptoms. Disease-related abnormalities in metabolites in plasma, urine or cerebral spinal fluid were identified in 40% of all patients whom underwent metabolic screening. In 52% the diagnosis led to identification of affected family members with the same IMD.
CONCLUSION
ES and/or GS is likely to yield an IMD diagnosis in adult patients presenting with an unexplained neurological phenotype, as well as in patients with a phenotype involving multiple organ systems. If a gene panel does not yield a conclusive diagnosis, it is worthwhile to analyze all known disease genes. Further prospective research is needed to establish the best diagnostic approach (type and sequence of metabolic and genetic test) in adult patients presenting with a wide range of symptoms, suspected of having an IMD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021295156.
PubMed: 37560457
DOI: 10.3389/fneur.2023.1206106 -
International Journal of Computer... Aug 2023The implementation of artificial intelligence in hand surgery and rehabilitation is gaining popularity. The purpose of this scoping review was to give an overview of... (Review)
Review
PURPOSE
The implementation of artificial intelligence in hand surgery and rehabilitation is gaining popularity. The purpose of this scoping review was to give an overview of implementations of artificial intelligence in hand surgery and rehabilitation and their current significance in clinical practice.
METHODS
A systematic literature search of the MEDLINE/PubMed and Cochrane Collaboration libraries was conducted. The review was conducted according to the framework outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. A narrative summary of the papers is presented to give an orienting overview of this rapidly evolving topic.
RESULTS
Primary search yielded 435 articles. After application of the inclusion/exclusion criteria and addition of supplementary search, 235 articles were included in the final review. In order to facilitate navigation through this heterogenous field, the articles were clustered into four groups of thematically related publications. The most common applications of artificial intelligence in hand surgery and rehabilitation target automated image analysis of anatomic structures, fracture detection and localization and automated screening for other hand and wrist pathologies such as carpal tunnel syndrome, rheumatoid arthritis or osteoporosis. Compared to other medical subspecialties the number of applications in hand surgery is still small.
CONCLUSION
Although various promising applications of artificial intelligence in hand surgery and rehabilitation show strong performances, their implementation mostly takes place within the context of experimental studies. Therefore, their use in daily clinical routine is still limited.
Topics: Humans; Artificial Intelligence; Carpal Tunnel Syndrome; Fractures, Bone; Hand; Image Processing, Computer-Assisted
PubMed: 36633789
DOI: 10.1007/s11548-023-02831-3 -
Frontiers in Immunology 2023Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of... (Meta-Analysis)
Meta-Analysis Review
The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis.
Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of neuropathic pain. Routine exercise has the potential to mitigate complications of future nerve damage and persistence of pain through neuroimmune regulation. This systematic review aimed to explore the effect of pre-injury exercise on neuroimmune responses, and other physiological and behavioural reactions following peripheral neuropathy in animals. Three electronic databases were searched from inception to July 2022. All controlled animal studies assessing the influence of an active exercise program prior to experimentally-induced traumatic peripheral neuropathy compared to a non-exercise control group on neuroimmune, physiological and behavioural outcomes were selected. The search identified 17,431 records. After screening, 11 articles were included. Meta-analyses showed that pre-injury exercise significantly reduced levels of IL-1β (SMD: -1.06, 95% CI: -1.99 to -0.13, n=40), but not iNOS (SMD: -0.71 95% CI: -1.66 to 0.25, n=82). From 72 comparisons of different neuroimmune outcomes at different anatomical locations, vote counting revealed reductions in 23 pro-inflammatory and increases in 6 anti-inflammatory neuroimmune outcomes. For physiological outcomes, meta-analyses revealed that pre-injury exercise improved one out of six nerve morphometric related outcomes (G-ratio; SMD: 1.95, 95%CI: 0.77 to 3.12, n=20) and one out of two muscle morphometric outcomes (muscle fibre cross-sectional area; SMD: 0.91, 95%CI: 0.27 to 1.54, n=48). For behavioural outcomes, mechanical allodynia was significantly less in the pre-injury exercise group (SMD -1.24, 95%CI: -1.87 to -0.61) whereas no overall effect was seen for sciatic function index. subgroup analysis suggests that timing of outcome measurement may influence the effect of pre-injury exercise on mechanical allodynia. Risk of bias was unclear in most studies, as the design and conduct of the included experiments were poorly reported. Preventative exercise may have potential neuroprotective and immunoregulatory effects limiting the sequalae of nerve injury, but more research in this field is urgently needed.
Topics: Animals; Hyperalgesia; Exercise; Neuralgia
PubMed: 37767095
DOI: 10.3389/fimmu.2023.1215566