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Background: Bartonella species are fastidious, intracellular bacteria responsible for an expanding array of human pathologies. Most are considered to be transmitted by direct inoculation with infected bodily fluids from a mammalian reservoir species or vector-transmitted through a variety of arthropod species and their excrement. However, there are mounting reports of infection in the absence of documented animal or vector contact. A variety of Bartonella species have been documented in conditions affecting both the peripheral and central nervous systems. More common conditions, including neuroretinitis, are often associated with Bartonella henselae. However, Bartonella quintana, the agent of trench fever, as well as emerging pathogens related to rodent reservoir species, B. grahamii and B. elizabethae, have also been documented. Encephalitis and encephalopathy, also most often associated with B. henselae, have been reported with B. quintana, B. washoensis (ground squirrels) and B. vinsonii subsp. vinsonii (voles) infections. Bartonella infections have also been associated with peripheral neuropathies, such as cranial nerve paresis and neuropathic pain, including infection with less commonly encountered species such as Bartonella koehlerae. Recently, molecular diagnostic testing revealed that DNA from Bartonella spp. was found to be more prevalent in blood of patients with neuropsychiatric disorders such as schizophrenia and psychoses compared to healthy controls. Methods: A systematic literature search was conducted on PubMed, Google Scholar and Web of Science. Search terms included Bartonella and specific neurological conditions and focused on peer-reviewed case reports published after 2012 pursuant to a prior review, with limited exceptions for conditions not previously covered. Published diagnostic testing, serology, molecular testing or pathology, were necessary for inclusion, except for one case which had clinical and epidemiological evidence consistent with diagnosis along with follow-up. Results: Neurobartonelloses included neuralgic amyotrophy, complex regional pain syndrome, chronic inflammatory demyelinating polyneuropathy, cranial nerve paralysis, Guillain-Barré syndrome, peripheral vasculitic polyneuropathy, acute transverse myelopathy, neuroretinitis, encephalitis/encephalopathy, cerebral vasculitis/aneurysm and neuropsychiatric conditions. Conclusions: The breadth of reported symptoms and clinical syndromes associated with an increasing number of Bartonella species continues to expand. Increased clinical awareness of this important zoonotic pathogen is necessary to advance One Health among the medical and veterinary communities. [ABSTRACT FROM AUTHOR]

Background: Approximately 70% of patients receiving neurotoxic chemotherapy (e.g., paclitaxel or vincristine) will develop chemotherapy-induced peripheral neuropathy. Despite the known negative effects of CIPN on physical functioning and chemotherapy dosing, little is known about how to prevent CIPN. The development of efficacious CIPN prevention interventions is hindered by the lack of knowledge surrounding CIPN mechanisms. Nicotinamide adenine dinucleotide (NAD+) and cyclic-adenosine diphosphate ribose (cADPR) are potential markers of axon degeneration following neurotoxic chemotherapy, however, such markers have been exclusively measured in preclinical models of chemotherapy-induced peripheral neuropathy (CIPN). The overall objective of this longitudinal, observational study was to determine the association between plasma NAD+, cADPR, and ADPR with CIPN severity in young adults receiving vincristine or paclitaxel. Methods: Young adults (18–39 years old) beginning vincristine or paclitaxel were recruited from Dana-Farber Cancer Institute. Young adults completed the QLQ-CIPN20 sensory and motor subscales and provided a blood sample prior to starting chemotherapy (T1) and at increasing cumulative vincristine (T2: 3–5 mg, T3: 7–9 mg) and paclitaxel (T2: 300–500 mg/m2, T3: 700–900 mg/m2) dosages. NAD+, cADPR, and ADPR were quantified from plasma using mass spectrometry. Metabolite levels and QLQ-CIPN20 scores over time were compared using mixed-effects linear regression models and/or paired two-sample tests. Results: Participants (N = 50) were mainly female (88%), white (80%), and receiving paclitaxel (78%). Sensory and motor CIPN severity increased from T1–T3 (p < 0.001). NAD+ (p = 0.28), cADPR (p = 0.62), and ADPR (p = 0.005) values decreased, while cADPR/NAD+ ratio increased from T1–T3 (p = 0.50). There were no statistically significant associations between NAD + and QLQ-CIPN20 scores over time. Conclusions: To our knowledge, this is the first study to measure plasma NAD+, cADPR, and ADPR among patients receiving neurotoxic chemotherapy. Although, no meaningful changes in NAD+, cADPR, or cADPR/NAD+ were observed among young adults receiving paclitaxel or vincristine. Future research in an adequately powered sample is needed to explore the clinical utility of biomarkers of axon degeneration among patients receiving neurotoxic chemotherapy to guide mechanistic research and novel CIPN treatments. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy (PN) is a common neurological complication of HIV (Human Immunodeficiency Virus) that can significantly affect patients' quality of life. In Ethiopia, children living with HIV are at an increased risk of developing peripheral neuropathy due to comorbidities such as anemia, tuberculosis, malnutrition, and poor socio-economic status. Our study aims to evaluate the prevalence of peripheral neuropathy among children living with HIV in Ethiopia using a simple clinical screening tool. Methods: A health institution-based cross-sectional study was conducted among 148 children aged 5 to 18 years living with HIV who are receiving treatment at the antiretroviral therapy (ART) clinic of the randomly selected public health institutions in the Gamo zone. An interview and neurologic examination were conducted. A binary logistic regression model was used to identify factors associated with the outcome variable. Variables with p-value < 0.25 in the bi-variable logistic regression analysis were entered and checked for association in a multivariable logistic regression model. The level of statistical significance was declared at the p-value < 0.05. Result: In this study, 148 children participated, making a response rate of 97.5%. The mean ± standard deviation (SD) age of the respondents was 15.03 ± 2.99 years, and 81(54.7%) were male. The magnitude of PN was 20.9% (31/148). Children in the age category of 15–18 (adjusted odds ratio (AOR) = 1.88, 95%CI; 1.24–4.60), low BMI for age (AOR = 1.66, 95%CI; 1.12–4.15), last exposure to isoniazid within 1 year (AOR = 2.31, 95%CI; 1.12–8.53). Longer duration of HIV illness (AOR = 2.17, 95%CI; 1.54–4.64), and past tuberculosis (TB) treatment (AOR = 2.11, 95%CI; 1.08–7.48) were significantly associated factors with peripheral neuropathy. Conclusion: Our analysis revealed that being in the age category of 15–18 years, low BMI for age, Isoniazid exposure, longer Duration of HIV illness, and past TB treatment were significantly associated with peripheral neuropathy in children living with HIV. These disease-related factors may contribute to the development and progression of peripheral neuropathy in this population. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: The previous effects of acupuncture-related interventions in improving chemotherapy-induced peripheral neuropathy (CIPN) symptoms and quality of life (QoL) remain unclear in terms of pairwise comparisons. Aims: This systematic review and network meta-analysis aimed to determine the hierarchical effects of acupuncture-related interventions on symptoms, pain, and QoL associated with CIPN in cancer patients undergoing chemotherapy. Methods: Nine electronic databases were searched, including PubMed, Embase, Cochrane Library, EBSCO, Medline Ovid, Airiti Library, China National Knowledge Infrastructure (CNKI), China Journal full-text database (CJFD), and Wanfang. Medical subject heading terms and text words were used to search for eligible randomized controlled trials published from database inception to May 2023. Results: A total of 33 studies involving 2,027 participants were included. Pairwise meta-analysis revealed that acupuncture-related interventions were superior to usual care, medication, or dietary supplements in improving CIPN symptoms, CIPN pain, and QoL. Furthermore, network meta-analysis indicated that acupuncture plus electrical stimulation (acupuncture-E) had the greatest overall effect among the various interventions. The surface under the cumulative ranking curve (SUCRA) revealed that acupuncture-E ranked the highest in improving CINP symptoms. Acupuncture alone was most effective in reducing CIPN pain, and acupuncture plus moxibustion (acupuncture-M) ranked highest in enhancing QoL. Conclusion: This finding suggests that acupuncture-related interventions can provide patients with benefits in improving CIPN symptoms, pain, and QoL. In particular, acupuncture-E could be the most effective approach in which the provided evidence offers diverse options for cancer patients and healthcare professionals. Implication for the profession and/or patient care: These findings provide valuable insights into the potential benefits of acupuncture-related interventions for managing symptoms, pain, and QoL associated with CIPN in patients undergoing chemotherapy. Among the various interventions studied, overall, acupuncture-E had the most significant impact and was effective for a minimum duration of 3 weeks. On the other hand, transcutaneous electrical acupoint/nerve stimulation (TEAS) was identified as a noninvasive and feasible alternative for patients who had concerns about needles or the risk of bleeding. It is recommended that TEAS interventions should be carried out for a longer period, preferably lasting 4 weeks, to achieve optimal outcomes. Trial registration: The study protocol was registered in the International Prospective Register of Systematic Reviews. Registration Number: CRD42022319871. [ABSTRACT FROM AUTHOR]

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: The white blood cell count to mean platelet volume ratio (WMR) is considered a promising inflammatory marker, and its recognition is increasing. Inflammation is closely related to metabolic diseases such as diabetes and its complications. However, there are currently no reports on the correlation between WMR and type 2 diabetic peripheral neuropathy (DPN). This study aims to explore the correlation between WMR and DPN in type 2 diabetes patients. By understanding this association, we hope to provide a theoretical basis for preventing DPN through the improvement of inflammatory responses. Methods: This was a cross-sectional study involving 2515 patients with T2DM. Logistic regression analysis was conducted to assess the associations between WMR and DPN. Finally, the receiver operating characteristic curve (ROC curve) was employed to evaluate the predictive efficacy of WMR for DPN. Results: Patients in higher WMR quartiles exhibited increased presence of DPN. Additionally, WMR remained significantly associated with a higher odds ratio (OR) of DPN (OR 4.777, 95% confidence interval [CI] 1.296–17.610, P < 0.05) after multivariate adjustment. Moreover, receiver operating characteristic curve analysis indicated that the optimal cutoff value for WMR in predicting DPN presence was 0.5395 (sensitivity: 65.40%; specificity: 41.80%; and area under the curve [AUC]: 0.540). Conclusions: In patients with T2DM, WMR was significantly increased in DPN and independently associated with an increased risk of DPN presence in Chinese patients. This suggests that WMR may serve as a useful and reliable biomarker of DPN, highlighting the importance of paying more attention to T2DM patients with high WMR to further prevent and reduce the development of DPN and related unfavorable health outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic offloading devices, including insoles, shoes, and other orthoses, are some of the most commonly used interventions to treat or prevent diabetic foot ulceration. Custom-made offloading devices are increasingly used to offset the development of foot ulcers. However, whether these devices are more effective than prefabricated standard offloading devices is uncertain. Therefore, this systematic review collates and examines evidence on the efficacy of custom-made offloading devices in preventing foot ulcer incidence and recurrence in people diagnosed with diabetes. Methods: Five scientific databases were searched, covering 2011–2023. Initial searches and screening were carried out independently by two researchers. Studies meeting the inclusion criteria were further examined through additional screenings, and critical appraisal. Data relevant to the review aims were extracted and analysed within a narrative synthesis. Results: Of the 1,715 articles found in the initial searches, nine papers were found to meet inclusion criteria and were included in the review. The evidence shows that custom-made offloading devices are likely to be more effective for reducing or preventing diabetic foot ulcers than standard offloading devices. However, due to a lack of data it remains uncertain whether custom-made offloading devices are more cost-effective for preventing ulceration compared to standard insoles. Likewise, due to measurement heterogeneity between studies and lack of data, it is unclear whether adherence is higher in users of custom-made offloading devices, and whether such devices deliver significantly greater reductions in peak pressure as compared to standard offloading devices. Conclusion: Custom-made offloading devices are more effective than standard devices for preventing diabetic foot ulceration, and we recommended their use when feasible; however, there remains uncertainty regarding their cost-effectiveness compared to standard insoles and offloading devices. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the long-term outcomes of saphenous nerve (SN) injuries from hamstring tendon harvesting during ACL reconstruction, focusing on clinical results and patient satisfaction after at least two years. Additionally, it investigates the incidence, recovery patterns, and impact of these injuries on functional outcomes, daily activities, and ACL re-rupture rates immediately post-surgery and at final follow-up. Materials and methods: A retrospective review was conducted on patients who had undergone ACL reconstruction with hamstring tendon grafts at a single institution between January 2015 and January 2020. The incidence of SN injuries was assessed immediately after surgery and at final follow-up. Additionally, the recovery rate and time were evaluated, and the impact of these injuries on functional outcomes was measured using the Lysholm Knee Score (LKS) and patient-reported effects on daily activities. Results: Of the 159 patients analyzed, iatrogenic SN injuries were initially observed in 87 (54.7%) patients post-ACLR. By the final follow-up, paresthesia had resolved in 36 (22.6%) patients within an average of 11.1 months. Persistent SN injuries were recorded in 51 (32.1%) patients, affecting various extents of the infrapatellar branch (IPBSN) and the sartorial branch (SBSN) of the saphenous nerve. Patients with persistent SN injuries experienced a significant impact on daily activities and had lower LKS scores compared to those without injuries or with recovered injuries. Furthermore, a higher re-rupture rate was associated with persistent SN injuries. Conclusions: The study finds that SN injuries during hamstring graft harvesting for ACL reconstruction are common, with a significant portion of patients experiencing persistent sensory deficits for at least two years postoperatively. These injuries are observed to adversely affect patient satisfaction and functional outcomes and to increase the re-rupture rate. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) and lower extremity arterial disease (LEAD) are significant contributors to diabetic foot ulcers (DFUs), which severely affect patients' quality of life. This study aimed to develop machine learning (ML) predictive models for DPN and LEAD and to identify both shared and distinct risk factors. Methods: This retrospective study included 479 diabetic inpatients, of whom 215 were diagnosed with DPN and 69 with LEAD. Clinical data and laboratory results were collected for each patient. Feature selection was performed using three methods: mutual information (MI), random forest recursive feature elimination (RF-RFE), and the Boruta algorithm to identify the most important features. Predictive models were developed using logistic regression (LR), random forest (RF), and eXtreme Gradient Boosting (XGBoost), with particle swarm optimization (PSO) used to optimize their hyperparameters. The SHapley Additive exPlanation (SHAP) method was applied to determine the importance of risk factors in the top-performing models. Results: For diagnosing DPN, the XGBoost model was most effective, achieving a recall of 83.7%, specificity of 86.8%, accuracy of 85.4%, and an F1 score of 83.7%. On the other hand, the RF model excelled in diagnosing LEAD, with a recall of 85.7%, specificity of 92.9%, accuracy of 91.9%, and an F1 score of 82.8%. SHAP analysis revealed top five critical risk factors shared by DPN and LEAD, including increased urinary albumin-to-creatinine ratio (UACR), glycosylated hemoglobin (HbA1c), serum creatinine (Scr), older age, and carotid stenosis. Additionally, distinct risk factors were pinpointed: decreased serum albumin and lower lymphocyte count were linked to DPN, while elevated neutrophil-to-lymphocyte ratio (NLR) and higher D-dimer levels were associated with LEAD. Conclusions: This study demonstrated the effectiveness of ML models in predicting DPN and LEAD in diabetic patients and identified significant risk factors. Focusing on shared risk factors may greatly reduce the prevalence of both conditions, thereby mitigating the risk of developing DFUs. [ABSTRACT FROM AUTHOR]

Background: Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes implemented during the study. We present a process evaluation protocol of a home-based gait, balance, and resistance exercise intervention to ameliorate persistent taxane-induced neuropathy study according to 7 key elements of process evaluation. Methods: The process evaluation is conducted parallel to the longitudinal, randomized control clinical trial examining the effects of the home-based gait, balance, and resistance exercise program for women with persistent peripheral neuropathy following treatment with taxanes for breast cancer (IRB approval: Pro00040035). The flowcharts clarify how the intervention should be implemented in comparable settings, fidelity procedures help to ensure the participants are comfortable and identify their individual needs, and the process evaluation allows for the individual attention tailoring and focus of the research to avoid protocol deviation. Conclusions: The publication of the evaluation protocol plan adds transparency to the findings of clinical trials and favors process replication in future studies. The process evaluation enables the team to systematically register information and procedures applied during recruitment and factors that impact the implementation of the intervention, thereby allowing proactive approaches to prevent deviations from the protocol. When tracking an intervention continuously, positive or negative intervention effects are revealed early on in the study, giving valuable insight into inconsistent results. Furthermore, a process evaluation adds a participant-centered element to the research protocols, which allows a patient-centered approach to be applied to data collection. Trial registration: ClinicalTrials.gov NCT04621721, November 9, 2020, registered prospectively. Protocol version: April 27, 2020, v2. [ABSTRACT FROM AUTHOR]

Background: Humeral shaft fractures, constituting 3–5% of musculoskeletal injuries, are commonly managed conservatively using functional braces. However, this approach may not be feasible in resource-limited settings. This study aimed to evaluate the functional outcomes of nonoperative treatment for humeral shaft fractures in adults utilizing a U-shaped slab. Methods: This prospective study was conducted from August 2021 to August 2022 involving 16-year-old and older individuals who received nonsurgical treatment for humeral shaft fractures at public tertiary hospitals in Rwanda. The assessment focused on various functional outcomes, including alignment, union rate, range of motion, return to activities of daily living, and DASH score. Results: The study included 73 participants, predominantly males (73.9%), with a median age of 33 years. The union rate was high at 89.04%, and 10.96% experienced delayed union. Radial nerve palsy occurred in 4.11% of patients, but all the patients fully recovered within three months. Despite angular deformities during healing in the majority of participants, these deformities did not significantly impact functional outcomes. According to the international classification of disabilities, 77% of participants achieved a good functional grade. Conclusion: The conservative U-shaped slab method was effective at managing humeral shaft fractures. However, optimal results necessitate careful participant selection and comprehensive rehabilitation education. Implementing these measures can improve the overall success of nonoperative management. [ABSTRACT FROM AUTHOR]

Background: A growing body of research indicates that poor functional status before chemotherapy may be correlated with the severity of chemotherapy-induced peripheral neuropathy (CIPN) after the neurotoxic treatment. However, little is known about the associations between pre-chemotherapy physical function and CIPN in patients with pancreatic cancer. Purpose: To identify the predictors of CIPN in relation to pre-chemotherapy physical function in patients with pancreatic cancer. Methods: This secondary analysis included data from patients with pancreatic cancer who participated in a longitudinal research study at National Cheng Kung University Hospital, Tainan, Taiwan. Four physical function tests (i.e., grip strength, Timed Up and Go (TUG), 2-minute step test (2MST), and Romberg test) and two questionnaires (The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and Chemotherapy-Induced Peripheral Neuropathy Module [CIPN20]) were assessed at baseline (i.e., before first chemotherapy session) and 2-, 3-, 4-, and 6-month follow-up. Multiple linear regression with adjustment for confounding factors was used to assess the associations between the four functional tests at baseline and the CIPN20 total score and individual subscale scores (sensory, motor, and autonomic) at 6-month follow-up. Results: Data from a total of 209 pancreatic cancer patients (mean age: 64.4 years, 54.5% male) were analyzed. The findings showed that the severity of CIPN at 6-month follow-up was significantly associated with the baseline TUG completion time (β = 0.684, p = 0.003). The TUG completion time was also positively correlated with the 6-month CIPN sensory and autonomic subscales. In addition, a baseline positive Romberg test (β = 0.525, p = 0.009) was a significant predictor of the severity of motor neuropathy at 6-month follow-up. Conclusion: The TUG completion time and positive Romberg test before chemotherapy may be predictive factors of the CIPN severity 6 months after the commencement of chemotherapy. Accordingly, the incorporation of TUG and Romberg tests into the clinical assessment protocol emerges as imperative for individuals diagnosed with pancreatic carcinoma undergoing chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Background: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. Methods: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. Results: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, l-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. Conclusion: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder. [ABSTRACT FROM AUTHOR]

Background: Unanticipated symptoms of peripheral nerve damage following surgery are distressing to both the patient and their clinical team, including surgeons, anesthesiologists, and neurologists. The causes that are commonly considered for perioperative neuropathy can include surgical trauma, positioning-related injury, or injury related to a regional anesthetic technique. However, these cases often do not have a clear etiology and can occur without any apparent periprocedural anomalies. Postoperative inflammatory neuropathy is a more recently described, and potentially underrecognized cause of perioperative neuropathy which may improve with corticosteroid therapy. Therefore, it is an important etiology to consider early in the evaluation of perioperative neuropathy. Case presentation: An otherwise healthy patient presented for left anterior cruciate ligament reconstruction. He underwent femoral and sciatic ultrasound-guided single-injection peripheral nerve blocks preoperatively, followed by a general anesthetic for the surgical procedure. He developed postoperative neuropathy in the sciatic distribution with both sensory and motor deficits. The patient received multi-disciplinary consultations, including neurology and pain management, and a broad differential diagnosis was considered. Based on neurological evaluation and imaging studies, a final diagnosis of post-surgical inflammatory neuropathy was made. The patient's course improved with conservative management, but immunosuppressive treatment may have been considered for a more severe or worsening clinical course. Conclusions: There are limited publications describing postoperative inflammatory neuropathy, and this case serves to illustrate a potentially under-recognized and multifactorial cause of postoperative neuropathy. Perioperative neuropathies are a complication that surgeons and anesthesiologists strive to avoid; however, prevention and treatment of this condition have been elusive. Increased reporting and investigation of postoperative inflammatory neuropathy as one cause for this complication will help to further our understanding of this potentially devastating complication. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) is a prevalent and serious complication of diabetes mellitus, impacting the nerves in the limbs and leading to symptoms like pain, numbness, and diminished function. While the exact molecular and immune mechanisms underlying DPN remain incompletely understood, recent findings indicate that mitochondrial dysfunction may play a role in the advancement of this diabetic condition. Methods: Two RNA transcriptome datasets (codes: GSE185011 and GSE95849), comprising samples from diabetic peripheral neuropathy (DPN) patients and healthy controls (HC), were retrieved from the Gene Expression Omnibus (GEO) database hosted by the National Center for Biotechnology Information (NCBI). Subsequently, differential expression analysis and gene set enrichment analysis were performed. Protein–protein interaction (PPI) networks were constructed to pinpoint key hub genes associated with DPN, with a specific emphasis on genes related to mitochondria and peripheral neuropathy disease (PND) that displayed differential expression. Additionally, the study estimated the levels of immune cell infiltration in both the HC and DPN samples. To validate the findings, quantitative polymerase chain reaction (qPCR) was employed to confirm the differential expression of selected genes in the DPN samples. Results: This research identifies four hub genes associated mitochondria or PN. Furthermore, the analysis revealed increased immune cell infiltration in DPN tissues, particularly notable for macrophages and T cells. Additionally, our investigation identified potential drug candidates capable of regulating the expression of the four hub genes. These findings were corroborated by qPCR results, reinforcing the credibility of our bioinformatics analysis. Conclusions: This study provides a comprehensive overview of the molecular and immunological characteristics of DPN, based on both bioinformatics and experimental methods. [ABSTRACT FROM AUTHOR]

Background Diabetic foot disease (DF) is a common diabetes-related complication; however, the prevalence and associated risk factors for DF are not well characterised among people living with diabetes (PLWD) in Zimbabwe. This may suggest the unavailability of adequate strategies to diagnose and treat DF in the country. This study aimed to determine the prevalence of DF and associated risk factors for PLWD in Harare, Zimbabwe. Methods This was a cross-sectional study, employing a quantitative approach. In total, 352 PLWD were recruited from 16 primary care clinics in Harare. Sociodemographic and clinical data were collected via face-to-face interviews and clinical records reviews. The DF screening included an evaluation for peripheral neuropathy, ankle-brachial index (ABI), ulceration, and amputation. Self-administered questionnaires were used to assess knowledge, attitudes, and practices (KAPs), and KAP was scored using Bloom’s cut-of. Chi-Square goodness-of-ft tests were performed, and regression analyses were used for association analysis. The threshold for signifcance was p<0.05. Results This group included 82 men and 279 women, with a combined mean age of 57.9±14 years. Twenty one (~26%) men and 41 (15%) women had type 1 diabetes. The diabetes type distribution signifcantly difered by gender (p<0.001). Oral hypoglycaemics (71%) were most commonly administered for management. DF was observed in 53% (95% CI=50–56) of PLWD. Other DF symptoms observed were abnormal ABI (53%), peripheral neuropathy (53%), foot ulceration (17%) and amputation (3%). Peripheral neuropathy increased the risk of ulceration (OR=1.7; 95% CI=1.1–2.6; p=0.019), while insulin use was protective against amputation (OR=0.1; 95% CI=0.1–0.9; p=0.049). Most (87%) of the participants demonstrated good DF knowledge and the importance of adhering to medication to prevent DF. However, 96% did not know that smoking was a risk factor for DF. Nearly two-thirds (63%) demonstrated poor attitudes and practices. Poor attitudes and practices were not predictors of DF ulceration risk (p>0.05). Conclusion This study showed that there was a high prevalence of DF (53%) in PLWD in Zimbabwe, and insulin use was protective against DF. There is an urgent need for policy revisions to include foot screening in routine primary care and increasing insulin use for PLWD to prevent complications such as DF as an integral part of primary care. Diabetic foot (DF) complications can lead to amputations, yet foot care is not routinely monitored in Zimbabwe. Our study describes the DF burden and the associated risk factors among people living with diabetes (PLWD) in Zimbabwe. More than half had DF, and 3% had amputated lower limbs. Insulin use was found to protect against amputations. Our study highlights the need for routine DF screening for PLWD. Our fndings also underscore the need for education and awareness tools for patients to adhere to prescribed insulin for improved diabetes management and prevention of complications such as DF. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) represents a major unmet medical need that currently has no preventive and/or curative treatment. This is, among others, driven by a poor understanding of the contributive role of drug transport across biological barriers to target-site exposure. Methods: Here, we systematically investigated the transport of 11 small-molecule drugs, both, associated and not with CIPN development, at conventional (dorsal root ganglia, sciatic nerve) and non-conventional (brain, spinal cord, skeletal muscle) CIPN sites. We developed a Combinatory Mapping Approach for CIPN, CMA-CIPN, combining in vivo and in vitro elements. Results: Using CMA-CIPN, we determined the unbound tissue-to-plasma concentration ratio (Kp,uu) and the unbound intracellular-to-extracellular concentration ratio (Kp,uu,cell), to quantitatively assess the extent of unbound drug transport across endothelial interfaces and parenchymal cellular barriers of investigated CIPN-sites, respectively, in a rat model. The analysis revealed that unique pharmacokinetic characteristics underly time-dependent accumulation of the CIPN-positive drugs paclitaxel and vincristine at conventional (dorsal root ganglia and sciatic nerve) and non-conventional (skeletal muscle) CIPN sites. Investigated CIPN-positive drugs displayed intracellular accumulation contrary to CIPN-negative drugs nilotinib and methotrexate, which lacked this feature in all investigated tissues. Conclusions: Hence, high unbound drug intracellular and extracellular exposure at target sites, driven by an interplay of drug transport across the endothelial and parenchymal cellular barriers, is a predisposing factor to CIPN development for CIPN-positive drugs. Critical drug-specific features of unbound drug disposition at various CIPN- sites provide invaluable insights into understanding the pharmacological/toxicological effects at the target-sites which will inform new strategies for monitoring and treatment of CIPN. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. Methods: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. Discussion: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. Trial registration: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023 [ABSTRACT FROM AUTHOR]

Background: Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination. Methods: We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering "Neuromuscular disease" AND "COVID-19 vaccine", and pooled the individual patient data extracted from the included studies. Results: A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%). The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based. Conclusion: COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination. Highlights: • Neuromuscular diseases (NMD) have emerged as a significant side effect of COVID-19 vaccination. • The study provides a comprehensive summary of the clinical features and outcomes of NMD associated with COVID-19 vaccination. • A total of 258 cases of NMD following COVID-19 vaccination were reported globally. • The most commonly reported NMDs were Guillain-Barré syndrome (GBS) and Parsonage-Turner syndrome (PTS). • Symptoms typically appeared within 2 weeks after vaccination, with a higher likelihood following the first dose of vector vaccine. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common adverse effect in patients undergoing chemotherapy, and no effective interventions are currently available for its prevention and treatment. Non-pharmacological therapies appear to be beneficial for the prevention and treatment of CIPN, but it remains unclear which therapy is most effective. The aim of this study was to identify the most effective non-pharmacological therapy for CIPN patients. Methods: PubMed, Web of Science, Embase, and Cochrane Library were searched for randomized controlled trials on non-pharmacological therapies for CIPN. The primary outcomes included pain and peripheral neuropathological symptoms, and the secondary outcomes included quality of life, sensory and motor symptoms. The pairwise analysis and a network meta-analysis were performed using a random effects model. Results: A total of 46 articles were included in this study, involving 2,878 participants. Our study showed that massage was more effective in pain-alleviating compared with acupuncture [SMD = 0.81, 95%CI (0.04, 1.57)], vitamin and gabapentin [SMD = 2.56, 95%CI (1.39, 3.74)], and usual care and placebo [SMD = 0.9, 95%CI (0.31, 1.49)]. As for attenuating peripheral neuropathological symptoms, massage was more effective than usual care and placebo [SMD = 0.75, 95%CI (0.33, 1.17)], sensorimotor training [SMD = 1.17, 95%CI (0.24, 2.10)], electrostimulation [SMD=-1.18, 95%CI (-2.14, -0.21)], multimodal exercise [SMD=-0.82, 95%CI (-1.57, -0.08)], and resistance training [SMD = 1.03, 95%CI (0.11, 1.95)]. Massage was also more effective than other non-pharmacological therapies in improving quality of life, sensory and motor symptoms. Conclusions: According to our study, massage has advantages in alleviating pain, improving quality of life, and improving peripheral neuropathological symptoms and has better effect than other non-pharmacological interventions, representing certain clinical significance. However, the results of this study should be interpreted with caution due to the limitations of the included studies. In the future, more high-quality multi arm randomized controlled trials can be attempted to provide direct comparisons of the relative effects of non-pharmacological interventions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of linezolid-containing regimens for treatment of M. abscessus pulmonary disease. Methods: The records of 336 patients with M. abscessus pulmonary disease who were admitted to Shanghai Pulmonary Hospital from January 2018 to December 2020 were retrospectively analyzed. A total of 164 patients received a linezolid-containing regimen and 172 controls did not. The effectiveness, safety, antibiotic susceptibility profiles, outcomes, culture conversion, cavity closure, and adverse reactions were compared in these two groups. Results: The two groups had similar treatment success (56.1% vs. 48.8%; P > 0.05), but treatment duration was shorter in the linezolid group (16.0 months [inter-quartile ranges, IQR: 15.0–17.0] vs. 18.0 months [IQR: 16.0–18.0]; P < 0.01). The rates of sputum culture conversion were similar (53.7% vs. 46.5%, P > 0.05), but time to conversion was shorter in the linezolid group (3.5 months [IQR: 2.5–4.4] vs. 5.5 months [IQR: 4.0–6.8]; P < 0.01). The linezolid group had a higher rate of cavity closure (55.2% vs. 28.6%, P < 0.05) and a shorter time to cavity closure (3.5 months [IQR: 2.5–4.4] vs. 5.5 months [IQR: 4.0–6.8]; P < 0.01). Anemia and peripheral neuropathy were more common in the linezolid group (17.7% vs. 1.7%, P < 0.01; 12.8% vs. 0.6%, P < 0.01). Conclusions: The linezolid and control groups had similar treatment success rates. The linezolid group had a shorter treatment duration, shorter time to sputum culture conversion, and higher rate and shorter time to lung cavity closure. More patients receiving linezolid developed anemia and peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes foot deformity is among the major causes of diabetic foot ulceration, resulting in lower limb amputation. However, the study on the distribution of foot deformity and its risk factor among diabetic patients in Ethiopia is limited. This study determined the overall prevalence and associated factors of foot deformity among adult diabetic patients on follow-up at Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia. Methods: Hospital-based cross-sectional study was conducted among 392 diabetic patients using a systematic random sampling technique at Debre Markos Comprehensive Specialized Hospital. Data were collected by pre-tested, semi-structured questionnaires and diabetic foot assessment format. Multivariable binary logistic regression was used to determine the association between dependent and independent variables. Adjusted odds ratios (AOR) with their 95% confidence interval (CI) were used to determine the strength of the association, and a variable with a p-value < 0.05 was statistically significant factors of diabetes foot deformity. Result: The overall prevalence of foot deformity was 33.4% [95% CI: 28.9–38.3]. In the final logistic regression analysis, rural residency [AOR = 2.64, 95% CI: 1.31, 5.31], poor glycemic control [AOR = 2.41; 95% CI: 1.34, 4.33], diabetes duration ≥ 10 years [AOR = 2.74; 95% CI: 1.50, 5.02], inadequate footwear [AOR = 2.11; 95% CI: 1.17, 3.82] and presence of peripheral neuropathy [AOR = 8.21; 95% CI: 4.54, 14.84] were statistically significant associated factors with diabetes foot deformity. Conclusion: The prevalence of foot deformity among adult diabetic patients was high. It is recommended to incorporate foot deformity screening in routine diabetic patient follow-ups especially for those with poor glycaemic control, rural residency, long diabetes duration, inadequate footwear, and diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain–Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: Interleg systolic blood pressure difference (ILSBPD) is associated with peripheral artery disease, but the relationship between ILSBPD and apparent peripheral neuropathy in diabetic patients remains unclear. We explored the relationship between ILSBPD and apparent peripheral neuropathy and examined the possible effect modifiers in US adults with diabetes. Methods: One thousand and fifty-one diabetic participants were included in the study with complete data on systolic blood pressure of the lower extremities and Semmes–Weinstein 10-g monofilament testing from the 1999–2004 National Health and Nutritional Examination Surveys. Systolic blood pressure in the lower extremities was measured using an oscillometric blood pressure device with the patient in the supine position. Apparent peripheral neuropathy was defined as the presence of monofilament insensitivity. Results: Every 5-mmHg increment in ILSBPD is associated with an about 14% increased risk of apparent peripheral neuropathy in crude model, but after adjustment for covariates, the correlation became nonsignificant (P = 0.160). When participants were divided into groups based on ILSBPD cutoffs of 5, 10 and 15 mmHg in different analyses, there was a significantly increased risk of apparent peripheral neuropathy in the ILSBPD ≥ 15 mmHg group (OR 1.79, 95% CI 1.11–2.91, P = 0.018), even after adjusting for confounders. In subgroup analysis, no interaction effect was found (all P for interaction > 0.05). Conclusions: In US adults with diabetes, an increase in the ILSBPD (≥ 15 mmHg) was associated with a higher risk of apparent peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: In nerve transfer for peripheral nerve injury, it is sometimes necessary to suture size-mismatched nerves. In 1993, a favorable suture method called the Ochiai suture method for size-mismatched nerve transfer was reported. However, there is currently a lack of substantial evidence beyond the original report. Therefore, this study aimed to verify the advantages of using the Ochiai suture method for size-mismatched nerve transfer. Methods: A total of 18 rats were evaluated in this study and randomly divided into two groups. All rats underwent femoral to sciatic nerve transfer. Specifically, group A (n = 10) underwent the Ochiai suture method, while group B (n = 8) underwent the perineural suture method. After 12 weeks postoperatively, we conducted the sciatic functional index (SFI) test, measured muscle wet-weight, and performed histological evaluations. All data were compared between the two groups, with Welch's t test for normally distributed data and Mann-Whitney's U test for non-normally distributed data. Statistical significance was set at p < 0.05. Results: The mean number of axons was significantly greater in group A than in group B at 5 mm distal to the stump (p = 0.04). Additionally, the average axonal diameter was significantly greater in group A than in group B at 5 mm and 10 mm distal to the stump (p < 0.01 and p < 0.01, respectively). However, the SFI test and measured muscle wet-weight values showed no significant differences between the two groups. Conclusions: Our study revealed that the Ochiai suture method for size-mismatched nerve transfer in rats increases the regenerative axon numbers and diameters. These findings suggest that the Ochiai suture method could be a valuable approach for achieving effective motor function restoration in cases of size-mismatched nerve transfer. [ABSTRACT FROM AUTHOR]

Background: Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations. Methods: This study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2–6 of chemotherapy. Cronbach's α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20. Result: A 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment – oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05). Conclusion: This study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks' intervention on chemotherapy completion and CIPN severity. Methods: Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline to week 12. Secondary endpoints included NRS scores for tingling and sleep, completion of chemotherapy, severity of CIPN, and quality of life (QOL) scores. The safety endpoint was incidence of adverse events. Results: Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), − 1.7 (− 2.4 to − 1.0) (p < 0.001). Patients with baseline NRS of ≥ 6 experienced a 44.0% reduction in score from baseline to week 12 (LOCF): mean change (95% CI), − 3.3 (− 5.0 to − 1.5) (p = 0.002). Chemotherapy was discontinued in 18 (34.6%) patients; CIPN led to discontinuation in only 2 (3.8%). There was no notable worsening of CIPN severity in terms of Common Terminology Criteria for Adverse Events grade or Modified Total Neuropathy Score-reduced, although use of pain medications during chemotherapy might cause worsening of CIPN due to underestimation of subjective symptoms. QOL score based on the EuroQol five-dimensional descriptive system did not worsen during the 12 weeks. Thirty-one percent of patients experienced adverse drug reactions, and the most common event was somnolence (13.5%). Serious adverse events and death occurred in 3 patients and 1 patient, respectively; however, they were unrelated to mirogabalin treatment. Conclusions: Intervention with mirogabalin during chemotherapy may be effective and safe for cancer patients with moderate to severe CIPN. It can contribute to completion of chemotherapy without worsening of CIPN. Trial registration: Japan Registry of Clinical Trials (jRCTs031210101, registered 20/5/2021). [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting side effect of systemic cancer therapy. In many cancer survivors, CIPN persists after treatment ends and is associated with functional impairments, abnormal gait patterns, falls, and diminished quality of life. However, little is known regarding which patients are most likely to develop CIPN symptoms that impair mobility and increase fall risk, when this risk develops, or the optimal timing of early intervention efforts to mitigate the impact of CIPN on functioning and fall risk. This study will address these knowledge gaps by (1) characterizing trajectories of symptoms, functioning, and falls before, during, and after treatment in adults prescribed neurotoxic chemotherapy for cancer; and (2) determining the simplest set of predictors for identifying individuals at risk for CIPN-related functional decline and falls. Methods: We will enroll 200 participants into a prospective, observational study before initiating chemotherapy and up to 1 year after completing chemotherapy. Eligible participants are aged 40–85 years, diagnosed with stage I-III cancer, and scheduled to receive neurotoxic chemotherapy. We perform objective assessments of vibratory and touch sensation (biothesiometry, tuning fork, monofilament tests), standing and dynamic balance (quiet stance, Timed-Up-and-Go tests), and upper and lower extremity strength (handgrip dynamometry, 5-time repeated chair stand test) in the clinic at baseline, every 4–6 weeks during chemotherapy, and quarterly for 1 year post-chemotherapy. Participants wear devices that passively and continuously measure daily gait quality and physical activity for 1 week after each objective assessment and self-report symptoms (CIPN, insomnia, fatigue, dizziness, pain, cognition, anxiety, and depressive symptoms) and falls via weekly electronic surveys. We will use structural equation modeling, including growth mixture modeling, to examine patterns in trajectories of changes in symptoms, functioning, and falls associated with neurotoxic chemotherapy and then search for distinct risk profiles for CIPN. Discussion: Identifying simple, early predictors of functional decline and fall risk in adults with cancer receiving neurotoxic chemotherapy will help identify individuals who would benefit from early and targeted interventions to prevent CIPN-related falls and disability. Trial registration: This study was retrospectively registered with ClinicalTrials.gov (NCT05790538) on 3/30/2023. [ABSTRACT FROM AUTHOR]

In recent years, the role of nobiletin in neuronal disorders has received extensive attention. However, the study of nobiletin in the peripheral nervous system is limited. Nobiletin, as a compound with high fat solubility, high bioavailability and low toxicity, has been extensively studied. Accumulating scientific evidence has shown that nobiletin has a variety of biological functions in the nervous system, such as inhibiting the expression of inflammatory factors, reducing the neurotoxic response, improving the antioxidant capacity, promoting the survival of nerve cells, promoting axon growth, reducing blood‒brain barrier permeability, reducing brain oedema, promoting cAMP response element binding protein expression, improving memory, and promoting mild depolarization of nerve cell mitochondria to improve antioxidative stress capacity. Accumulating studies have shown that nobiletin also protects enteric nervous system, spinal cord and sciatic nerve. To explore the new therapeutic potential of nobiletin in the nervous system, recent and relevant research progress is reviewed in this article. This will provide a new research idea for nobiletin in the nervous system. [ABSTRACT FROM AUTHOR]

Background: We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept. Methods: Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables. Results: The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product. Conclusions: Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory. Trial registration: ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy is not only the most prevalent consequence of diabetes but also the main reason for foot ulceration, disability, and amputation. Therefore, the current study aims to determine the effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients. Methods: This 12-week, randomized, and parallel-group trial was conducted to compare the efficacy of oral clonidine and gabapentin with gabapentin alone in diabetic patients in southwest Iran during the first half of 2021. Thirty patients with type 2 diabetes with peripheral neuropathy as assessed by a visual analog scale (VAS) and divided into two groups of 15 patients, treated for up to three months. The data were analyzed using SPSS-21 software. In order to report the results, descriptive indices, independent t-test, one-way analysis of covariance (ANCOVA) and analysis of variance with repeated measures were used. Results: The mean and standard deviation of the age of the participants in the clonidine + gabapentin group was equal to 50.20 ± 7.44, and in the gabapentin group was equal to 50.47 ± 7.57 (t = 0.10, P-value = 0.923). This research showed a significant difference between the clonidine + gabapentin group and with gabapentin group in terms of neuropathic pain and the severity of neuropathic pain (P < 0.001). Conclusions: According to this research results, clonidine + gabapentin can reduce neuropathic pain and the severity of neuropathic pain in diabetic patients. Therefore, it is recommended that healthcare professionals with diabetes expertise prescribe these medications to reduce neuropathic pain and its severity. Trial registration: This study was registered in the Iranian Clinical Trials System with the ID (IRCT20211106052983N1) on 14/01/2022. [ABSTRACT FROM AUTHOR]

Background: The morbidity of type 1 diabetes mellitus (T1DM) in children is increasing and diabetic peripheral neuropathy (DPN) is one of the main microvascular complications of T1DM. The aim of this study was to explore sympathetic skin response (SSR) characteristics in children with T1DM and analyze the value of early diagnosis and follow-up in T1DM complicated with DPN. Methods: Our prospective study enrolling 85 participants diagnosed with T1DM and 30 healthy controls (HCs) in the Children's Hospital of Hebei Province from 2017 to 2020. Compared the outcomes of SSR and nerve conduction study (NCS) in T1DM, and evaluated the variations in SSR and NCS of different durations, as well as changes after six months of therapy. Results: SSR latency of T1DM group showed statistical difference as compared to HCs (p < 0.05). The SSR test was more sensitive than the NCS test in the early diagnosis of T1DM with DPN (p < 0.05). The abnormal rates of SSR and NCS in long duration of disease were higher than those in short duration of disease (p < 0.05). Among 65 participants with diabetic neuropathy, the onset latencies of SSR were shortened and the NCS were improved after treatment (p < 0.05). Conclusions: SSR could provide the accurate early diagnosis and follow-up of pediatric diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) has been shown to be independently associated with cardiovascular events and mortality. This study aimed to evaluate changes in left ventricular (LV) microvascular perfusion and myocardial deformation in type 2 diabetes mellitus (T2DM) patients with and without DPN, as well as to investigate the association between myocardial perfusion and LV deformation. Methods: Between October 2015 and July 2022, one hundred and twenty-three T2DM patients without DPN, fifty-four patients with DPN and sixty age‑ and sex‑matched controls who underwent cardiovascular magnetic resonance imaging were retrospectively analyzed. LV myocardial perfusion parameters at rest, including upslope, time to maximum signal intensity (TTM), max signal intensity (max SI), and myocardial strains, including global radial, circumferential and longitudinal strain (GRS, GCS and GLS, respectively), were calculated and compared among the groups with One‑way analysis of variance. Univariable and multivariable linear regression analyses were performed to explore the independent factors influencing LV myocardial perfusion indices and LV strains in diabetes. Results: The LV GLS, upslope and max SI were significantly deteriorated from controls, through patients without DPN, to patients with DPN (all P < 0.001). Compared with controls, TTM was increased and LV GRS and GCS were decreased in both patient groups (all P < 0.05). Multivariable regression analyses considering covariates showed that DPN was independently associated with reduced upslope, max SI and LV GLS (β = − 0.360, − 2.503 and 1.113, p = 0.021, 0.031 and 0.010, respectively). When the perfusion indices upslope and max SI were included in the multivariable analysis for LV deformation, DPN and upslope (β = 1.057 and − 0.870, p = 0.020 and 0.018, respectively) were significantly associated with LV GLS. Conclusion: In patients with T2DM, there was more severe LV microvascular and myocardial dysfunction in patients with complicated DPN, and deteriorated subclinical LV systolic dysfunction was associated with impaired myocardial circulation. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora. Methods: In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis. Results: HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis. Conclusions: HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphoproliferative disorders of natural killer cells (CLPD-NK) is a rare lymphoproliferative disease. Peripheral neuropathy is an unusual symptom of CLPD-NK. We report a case of peripheral neuropathy associated with CLPD-NK and perform a review of literatures. Case presentation: a 62-year‐old woman presented with progressive numbness and weakness in both extremities. Electrophysiological examinations indicated a sensorimotor polyneuropathy. Peripheral blood examination revealed that the number of white blood cells (WBC) and lymphocytes were significantly increased. Flow cytometry analysis identified that 84% of the lymphocytes are NK cells that mainly expressed CD56, combined with variable expression of CD16, CD2, CD7, CD94, granzyme B, perforin, and CD158 but negative for CD3. Sural nerve biopsy revealed that a plethora of NK cells infiltrated into nerve fascicles. On treatment with combined cyclophosphamide and corticosteroids, her symptoms rapidly improved. Moreover, the absolute lymphocyte count and its proportion recovered to normal range after 3 months' treatment. Conclusion: To the best of our knowledge, this is the first case report of peripheral neuropathy associated with CLPD-NK from Chinese. This rare lymphoproliferative disease should be considered if peripheral neuropathy combines with increased WBC or lymphocytes. Immunosuppressive drugs are the major treatment and most patients can achieve a good prognosis. [ABSTRACT FROM AUTHOR]

Background and purpose: The lack of timely foot care among individuals with diabetics often lead to ulceration followed by infection and amputation. This study aimed to evaluate the foot self-care status and foot screening practices among patients with type 2 diabetes in various cities across Iran. Methods: The cross-sectional descriptive study was performed on patients with type 2 diabetes in 10 main cities of Iran. The information about demographic and lifestyle factors, diabetes history, and diabetic foot self-care (DFSQ) was assessed. Additionally, the neurological and vascular condition of the foot were screened by Inlow's 60-Second Screen. Results: The study included 1094 diabetic patients with, with a majority being female (64.8%) and married (92.5%). The average age of the participants was 57.6 ± 10.21 (mean ± SD), and the mean duration of diabetes was 11.56 ± 7.41 years. Based on Inlow's 60-Second Screen criteria, 58% of the patients should undergo yearly foot ulcer screening, 47% exhibited peripheral neuropathy, and 37% were found to have inappropriate footwear. Conclusion: The high prevalence of peripheral neuropathy observed in approximately half of the participants across different regions of Iran underscores the importance of continuous patient education regarding foot care and appropriate footwear. Furthermore, regular foot ulcer screenings, following the recommended intervals outlined in Inlow's screening protocol, should be implemented to effectively manage diabetic foot complications. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions. Case presentation: A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient's immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30–35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy. Conclusion: The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative. [ABSTRACT FROM AUTHOR]

The present study was undertaken to explore the relative contributions of Cav3.2 T-type channels to mediating the antihyperalgesic activity of joint manipulation (JM) therapy. We used the chronic constriction injury model (CCI) to induce peripheral neuropathy and chronic pain in male mice, followed by JM. We demonstrate that JM produces long-lasting mechanical anti-hyperalgesia that is abolished in Cav3.2 null mice. Moreover, we found that JM displays a similar analgesic profile as the fatty acid amide hydrolase inhibitor URB597, suggesting a possible converging mechanism of action involving endocannabinoids. Overall, our findings advance our understanding of the mechanisms through which JM produces analgesia. [ABSTRACT FROM AUTHOR]

Background: Increased levels of low-density lipoprotein cholesterol (LDL-C) have been identified as one potential risk factor for diabetic peripheral neuropathy (DPN) in patients. The current study seeks to clarify the link between LDL-C, hyperglycemia, and DPN in patients with type 2 diabetes mellitus (T2DM). Methods: Here, a total of 120 T2DM individuals were recruited. These volunteers with T2DM were divided into 2 groups, based on the presence or absence of peripheral neuropathy. Additionally, their baseline characteristics were compared. Association among LDL-C and glycosylated hemoglobin (HbA1c) levels and DPN, particularly with respect to specific nerve conduction velocity were analyzed. To identify factors influencing DPN, regression was performed. Furthermore, mediation analysis was employed to evaluate the indirect, direct and total effects of LDL-C on specific nerve conduction velocity, with HbA1c serving as a mediator. Results: Compared to 55 patients without DPN, 65 patients with DPN demonstrated elevated levels of LDL-C and HbA1c. Both LDL-C and HbA1c have been found to be associated with reduced the motor fiber conduction velocities of Ulnar (or the Common peroneal) nerve in diabetic patients. HbA1c is one of the known risk factors for DPN in individuals with T2DM. Further mediation analysis revealed that the effect of LDL-C on the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities are fully mediated by HbA1c in patients with T2DM. Conclusions: The impact of elevated LDL-C levels upon the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities in patients with T2DM was found to be entirely mediated by increased HbA1c levels. [ABSTRACT FROM AUTHOR]

Background: Diabetic cardiovascular autonomic neuropathy (CAN) and distal symmetrical polyneuropathy (DSPN) are severe diabetic complications. Collagen type VI (COL6) and III (COL3) have been associated with nerve function. We investigated if markers of COL6 formation (PRO-C6) and COL3 degradation (C3M) were associated with neuropathy in people with type 1 diabetes (T1D). Methods: In a cross-sectional study including 300 people with T1D, serum and urine PRO-C6 and C3M were obtained. CAN was assessed by cardiovascular reflex tests: heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuver (VM). Two or three pathological CARTs constituted CAN. DSPN was assessed by biothesiometry. Symmetrical vibration sensation threshold above 25 V constituted DSPN. Results: Participants were (mean (SD)) 55.7 (9.3) years, 51% were males, diabetes duration was 40.0 (8.9) years, HbA1c was 63 (11 mmol/mol, (median (IQR)) serum PRO-C6 was 7.8 (6.2;11.0) ng/ml and C3M 8.3 (7.1;10.0) ng/ml. CAN and DSPN were diagnosed in 34% and 43% of participants, respectively. In models adjusted for relevant confounders a doubling of serum PRO-C6, was significantly associated with odds ratio > 2 for CAN and > 1 for DSPN, respectively. Significance was retained after additional adjustments for eGFR only for CAN. Higher serum C3M was associated with presence of CAN, but not after adjustment for eGFR. C3M was not associated with DSPN. Urine PRO-C6 analyses indicated similar associations. Conclusions: Results show previously undescribed associations between markers of collagen turnover and risk of CAN and to a lesser degree DSPN in T1D. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy caused by amyloidosis is one of the well-recognised sequelae of mutations in the transthyretin gene (TTR). Case presentation: We describe a case of peripheral neuropathy in a White British 74 year old man with wild-type TTR, 8 years following receipt of a 'domino' liver transplant (from a donor with a TTR mutation). The clinical phenotype and neurophysiology, coupled with presence of ATTR amyloid deposits on fat biopsy, established the diagnosis of ATTR amyloid neuropathy, as a consequence of receipt of a variant-TTR secreting liver. A nerve biopsy was not clinically appropriate for this patient. Such cases are rare since recipients of such livers are typically restricted to people whose natural lifespan is unlikely to stretch into the anticipated symptomatic period of ATTR amyloidosis. However, novel "gene silencing" therapeutics are now available which can dramatically alter the course of this disorder, by reducing the proportion of abnormal proteins. Conclusions: This represents a rare but predictable iatrogenic side effect, and doctors should be aware of this eventuality occurring in a shorter time span than previously anticipated. [ABSTRACT FROM AUTHOR]

Background: Dose-limiting toxicities significantly impact the benefit/risk profile of many drugs. Whole genome sequencing (WGS) in patients receiving drugs with dose-limiting toxicities can identify therapeutic hypotheses to prevent these toxicities. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting neurological toxicity of chemotherapies with no effective approach for prevention. Methods: We conducted a genetic study of time-to-first peripheral neuropathy event using 30× germline WGS data from whole blood samples from 4900 European-ancestry cancer patients in 14 randomized controlled trials. A substantial number of patients in these trials received taxane and platinum-based chemotherapies as part of their treatment regimen, either standard of care or in combination with the PD-L1 inhibitor atezolizumab. The trials spanned several cancers including renal cell carcinoma, triple negative breast cancer, non-small cell lung cancer, small cell lung cancer, bladder cancer, ovarian cancer, and melanoma. Results: We identified a locus consisting of low-frequency variants in intron 13 of GRID2 associated with time-to-onset of first peripheral neuropathy (PN) indexed by rs17020773 (p = 2.03 × 10−8, all patients, p = 6.36 × 10−9, taxane treated). Gene-level burden analysis identified rare coding variants associated with increased PN risk in the C-terminus of GPR68 (p = 1.59 × 10−6, all patients, p = 3.47 × 10−8, taxane treated), a pH-sensitive G-protein coupled receptor (GPCR). The variants driving this signal were found to alter predicted arrestin binding motifs in the C-terminus of GPR68. Analysis of snRNA-seq from human dorsal root ganglia (DRG) indicated that expression of GPR68 was highest in mechano-thermo-sensitive nociceptors. Conclusions: Our genetic study provides insight into the impact of low-frequency and rare coding genetic variation on PN risk and suggests that further study of GPR68 in sensory neurons may yield a therapeutic hypothesis for prevention of CIPN. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. Methods: This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II–III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. Discussion: This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. Trial registration: ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023. [ABSTRACT FROM AUTHOR]

Background: Insulinomas are rare neuroendocrine tumors that typically present with hypoglycemic crises. Peripheral neuropathy is an uncommon complication of insulinoma. Most clinicians expect peripheral neuropathy symptoms to reverse completely after the insulin-secreting tumor is resected, but this may be a misassumption. Case report: We report a case of a 16-year-old Brazilian boy with clonic muscle spasms of the lower limbs for almost one year. Disabling paraparesis and confusional episodes had progressively set in as well. There were no sensorial abnormalities in the lower limbs, upper limbs or cranial nerves. An electromyography revealed a motor neuropathy of the lower limbs. The diagnosis of insulinoma was established as serum insulin and C-peptide concentrations were inappropriately normal during spontaneous episodes of hypoglycemia. Following a normal abdominal magnetic resonance scan, the imaging work-up continued with an endoscopic ultrasound, which localized the tumor at the pancreatic body-tail transition. Once localized, a prompt surgical removal (enucleation) of the tumor was undertaken, leading to an immediate and complete resolution of hypoglycemia. The time length between the onset of symptoms and tumor resection was 15 months. After surgery, the symptoms of peripheral neuropathy of the lower limbs showed a slow and only partial improvement. At a two-year follow-up after surgery, although being able to lead a normal and productive life, the patient still reported symptoms of reduced muscular strength in the lower limbs and a new electroneuromyography analysis showed chronic denervation and reinnervation in the legs' muscles—indicating chronic neuropathic injury. Conclusion: The events of this case reinforce the importance of an agile diagnostic work-up and spry definitive treatment for patients with this uncommon disease, enabling the cure of neuroglycopenia before permanent bothersome complications ensue. [ABSTRACT FROM AUTHOR]

Background: We reported on a case involving an older patient with HSV-1 encephalitis who simultaneously experienced the onset of peripheral nerve symptoms associated with the presence of anti-GM3 immunoglobulin G (IgG). Case presentation: A 77-year-old male was admitted to hospital with high fever, weakness of both lower limbs, and an unstable gait. A CSF test revealed a strikingly increased protein level (1,002 mg/L, normative values: 150-450 mg/L) and MRI revealed hyper-signal lesions in the right temporal lobe, right hippocampus, right insula, and right cingulate gyrus. The CSF was positive for HSV PCR (HSV-1,17870). In addition, the serum samples were positive for CASPR2 antibodies (antibody titer: 1/10) and anti-GM3 immunoglobulin G (IgG) (+). The patient was diagnosed with HSV-1-induced peripheral nerve symptoms that were associated with encephalitis and the presence of anti-GM3 IgG and anti-CASPR2 antibodies. The patient had received included intravenous immunoglobulin, intravenous acyclovir, and corticosteroids therapy. At the one-year follow-up examination, he had regained the necessary skills associated with daily life. Conclusions: Herpes simplex virus infection often induces encephalitis, and reaction to the virus may trigger an autoimmune response. Early diagnosis and treatment can avoid the progression of the disease to include autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

We analyzed single nucleotide polymorphisms (SNPs) in PKNOX1 (rs2839629) and in the intergenic region between PKNOX1 and CBS (rs915854) by Sanger sequencing in 88 patients with multiple myeloma treated with bortezomib. All patients (n = 13) harboring a homozygous mutation in PKNOX1 (rs2839629) also had a homozygous mutated rs915854 genotype. Homozygous mutated genotypes of rs2839629 and rs915854 were significantly enriched in patients with painful peripheral neuropathy (PNP) (P < 0.0001), and homozygous mutated rs2839629 genotype was significantly enriched in patients with pain compared to patients with no pain (P = 0.04). In summary, both SNPs rs2839629 and/or rs915854 may be potential biomarkers predicting an increased risk to develop painful PNP under bortezomib. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorders (NMOSD) is a group of autoimmune-mediated disorders of the central nervous system primarily involving the optic nerve and spinal cord. There are limited reports of NMOSD associated with peripheral nerve damage. Case presentation: We report a 57-year-old female patient who met the diagnostic criteria for aquaporin 4 (AQP4)-IgG positive NMOSD with undifferentiated connective tissue disease and multiple peripheral neuropathy. In addition, the patient was positive for multiple anti-ganglioside antibodies (anti-GD1a IgG antibodies and anti-GD3 IgM antibodies) and anti-sulfatide IgG antibodies in serum and cerebrospinal fluid. After treatment with methylprednisolone, gamma globulin, plasma exchange, and rituximab, the patient's status improved and was subsequently discharged from our hospital. Conclusions: The neurologist should be aware of the unusual association between NMOSD and immune-mediated peripheral neuropathy undifferentiated connective tissue disease and nerve damage mediated by multiple antibodies may have combined to cause peripheral nerve damage in this patient. [ABSTRACT FROM AUTHOR]

Background: Diabetes causes impaired microarterial blood flow, demyelination and neuronal damage, which may lead to cochlear damage and vestibular malfunction. Vestibular evoked myogenic potentials (VEMP) is a simple, reproducible test. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) can be explored in the saccadic-spinal and utriculo-ocular pathways in regular clinical practice. Objective: To evaluate possible vestibular evoked myogenic potential (VEMP) abnormalities in patients with diabetic peripheral neuropathy. Materials and methods: 89 patients with Type 2 Diabetes in the present study consisted of three groups: 29 patients with no peripheral neuropathy (NDPN group), 26 patients with asymptomatic neuropathy (SDPN group), 34 patients with symptomatic neuropathy (DPN group). Meanwhile, 42 healthy subjects were recruited as controls. The clinical characteristics (including gender, age, body mass index (BMI), and illness duration), as well as lipids (including triglyceride (TG), cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)), uric acid, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) were compared among the four groups. Four groups were assessed using two vestibular tests including oVEMP and cVEMP. Latency and amplitude parameters were analyzed from VEMP plots. Results: The latency of n10, p15 (oVEMP), p13, n23 (cVEMP) were significantly prolonged in the SDPN and DPN groups compared with the control and NDPN groups (p < 0.01), whereas latencies were similar in NDPN and the control groups. The amplitudes were not significantly different (p > 0.05). oVEMP latency p15 and cVEMP latency (p13, n23) were positively correlated with HbA1c, FBG, and illness duration, and oVEMP latency n10 was positively correlated with HbA1c and FBG. A nomogram, including FBG, HbA1C, HDL, TG, TC, LDL and group, was constructed to predict VEMP parameters and p13 was found to be independently associated with diabetic subgroups. Receiver operating characteristic curve (ROC) analysis showed good accuracy in predicting p13 in this nomogram. A user-friendly website has been created to facilitate the application of this prediction model (https://fyey.shinyapps.io/VEMP%5fModel/). Conclusion: Patients with diabetic peripheral neuropathy may have vestibular dysfunction. VEMP may be useful in assessing vestibular impairment in diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular disease and peripheral neuropathy may cause drop foot with or without evertor weakness. We developed a helical-shaped, non-articulated ankle–foot orthosis (AFO) to provide medial–lateral stability while allowing mobility, to improve gait capacity. Our aim was to evaluate the effect of the helical AFO (hAFO) on functional gait capacity (6-min walk test) in people with peripheral neuropathy or neuromuscular disease (NMD) causing unilateral drop foot and compare with a posterior leaf spring AFO (plsAFO). Secondary aims were to compare functional mobility, 3D kinematic and kinetic gait variables and satisfaction between the AFOs. Methods: Single centre, randomised crossover trial from January to July 2017 in 20 individuals (14 with peripheral neuropathy and 6 with NMD, 12 females, mean age 55.6 years, SD 15.3); 10 wore the hAFO for the first week and 10 wore the plsAFO before switching for the second week. The 6-min walk test (6MWT), Timed Up and Go (TUG) test and 3D gait analysis were evaluated with the hAFO, the plsAFO and shoes only (noAFO) at inclusion and 1 week after wearing each orthosis. Satisfaction was evaluated with the Quebec user evaluation of satisfaction with assistive technology (QUEST). Results: Median [interquartile range] 6MWT distance was greater with the hAFO (444 m [79]) than the plsAFO (389 m [135], P < 0.001, Hedge's g = 0.6) and noAFO (337 m [91], P < 0.001, g = 0.88). TUG time was shorter with the hAFO (8.1 s [2.8]) than the plsAFO (9.5 s [2.6], P < 0.001, g = − 0.5) and noAFO (10.0 s [2.6]), P < 0.001, g = − 0.6). The plsAFO limited plantarflexion during the loading response (plsAFO − 7.5 deg [6.0] vs. noAFO -13.0 deg [10.0], P = 0.0007, g = − 1.0) but the hAFO did not (− 11.0 deg [5.1] vs. noAFO, P = 0.05, g = − 0.5). Quasi-stiffness was lower for the hAFO than plsAFO (P = 0.009, g = − 0.7). The dimensionless eversion moment was higher (though not significantly) with the hAFO than noAFO. Neither orthosis reduced ankle power (P = 0.34). Median total QUEST score was higher for the hAFO (4.7 [0.7]) than the plsAFO (3.6 [0.8]) (P < 0.001, g = 1.9). Conclusions: The helical orthosis significantly and considerably improved functional gait performance, did not limit ankle mobility, increased lateral stability, though not significantly, and was associated with greater patient satisfaction than the posterior leaf spring orthosis. Trial registration The trial began before registration was mandatory [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of chemotherapy with poorly understood mechanisms and few treatments. High-mobility group box 1 (HMGB1)-induced neuroinflammation is the main cause of CIPN. Here, we aimed to illustrate the role of the macrophage scavenger receptor A1 (SR-A1) in HMGB1 clearance and CIPN resolution. Methods: Oxaliplatin (L-OHP) was used to establish a CIPN model. Recombinant HMGB1 (rHMGB1) (his tag) was used to evaluate the phagocytosis of HMGB1 by macrophages. Results: In the clinic, HMGB1 expression and MMP-9 activity were increased in the plasma of patients with CIPN. Plasma HMGB1 expression was positively correlated with the cumulative dose of L-OHP and the visual analog scale. In vitro, engulfment and degradation of rHMGB1 increased and inflammatory factor expression decreased after AMP-activated protein kinase (AMPK) activation. Neutralizing antibodies, inhibitors, or knockout of SR-A1 abolished the effects of AMPK activation on rHMGB1 engulfment. In vivo, AMPK activation increased SR-A1 expression in the dorsal root ganglion, decreased plasma HMGB1 expression and MMP-9 activity, and attenuated CIPN, which was abolished by AMPK inhibition or SR-A1 knockout in the CIPN mice model. Conclusion: Activation of the AMPK/SR-A1 axis alleviated CIPN by increasing macrophage-mediated HMGB1 engulfment and degradation. Therefore, promoting HMGB1 clearance may be a potential treatment strategy for CIPN. 1JEzHJvY7WaTcecv7_-Z6v Video abstract [ABSTRACT FROM AUTHOR]