Peripheral Neuropathy In Patients Research Articles

The association between hyperlipidemia, lipid-lowering drugs and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus.

Previous studies showed conflicting relationship between hyperlipidemia, lipid-lowering therapy and diabetic peripheral neuropathy (DPN). As most of these works emerges from the Western and Australian countries, our study aims to investigate whether hyperlipidemia or lipid-lowering therapy (LLT) is associated with DPN in Taiwanese patients with type 2 diabetes (T2D). A cross-sectional, hospital-based observation study in adults with T2D was conducted from January to October 2013. DPN was screened using the Michigan Neuropathy Screening Instrument. Data were obtained at the time of enrollment, including medication usage, anthropometric measurements and laboratory examinations. 2,448 participants were enrolled, 524 (21.4%) of whom had DPN. Patients with DPN had significantly lower plasma total cholesterol (185.6 ± 38.6 vs 193.4 ± 42.3 mg/dL) and low-density lipoprotein cholesterol levels (114.6 ± 32.7 vs 119 ± 30.8 mg/dL). Multivariate analysis demonstrated that neither hyperlipidemia (adjusted OR (aOR), 0.81; 95% confidence interval (CI), 0.49-1.34) nor LLT (aOR, 1.10; 95% CI, 0.58-2.09) was associated with DPN. Subgroup analysis revealed that neither total cholesterol (aOR, 0.72; 95% CI, 0.2-2.62), low-density lipoprotein cholesterol levels (aOR, 0.75; 95% CI, 0.2-2.79), statin (aOR, 1.09; 95% CI, 0.59-2.03) nor fibrate (aOR, 1.73; 95% CI, 0.33-1.61) was associated with DPN. Our results suggest that neither hyperlipidemia nor lipid-lowering medication was associated with DPN in adults with T2D. DPN is a multifactorial disease, and our findings indicate that lipid metabolism may play a minor role in its pathogenesis.

Effect of Cilostazol on Preventing Paclitaxel-Induced Neuropathy in Patients with Breast Cancer: A Randomized Controlled Trial.

Paclitaxel-induced peripheral neuropathy is a significant clinical problem can markedly deteriorate patient's quality of life (QoL). Preclinical evidence exists about the preventive capacity of cilostazol against peripheral neuropathy. However, this hypothesis has not yet been clinically investigated. This proof-of-concept study evaluated the effect of cilostazol on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer. This study is a parallel randomized placebo-controlled trial. Patients (n=69) with breast cancer scheduled to receive paclitaxel 175 mg/m2 biweekly were randomized to either cilostazol group who received cilostazol tablets 100 mg BID, or to control group who received placebo instead. The primary endpoint was the incidence of paclitaxel-induced neuropathy evaluated through common terminology criteria for adverse event (NCI-CTCAE) version 4. Secondary endpoints included assessment of the patient's QoL by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Exploratory outcome measures included changes in serum levels of biomarkers namely nerve growth factor (NGF), and neurofilament light chain (NfL). The incidence of grade two, and three peripheral neuropathies were significantly lower in the cilostazol group (40%) compared to control group (86.7%) (P < 0.001). The incidence of clinically significant worsening in neuropathy related QoL was higher in control group compared to cilostazol group (P = 0.001). A higher percent increase from baseline in serum NGF was observed in the cilostazol group (P = 0.043). The circulating levels of NfL deemed comparable between the two arms at the end of the study (P = 0.593). Adjunctive use of cilostazol may be considered as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL. Future larger clinical trials are warranted to confirm these findings.

Efficacy of cryotherapy on chemotherapy-induced peripheral neuropathy in patients with breast cancer: a propensity score-matched study.

This study investigated the effectiveness of cryotherapy in preventing CIPN and its effect on the quality of life (QoL) during chemotherapy. Eligible participants are cancer patients who began therapy with carboplatin, docetaxel, or paclitaxel in the Breast Oncology Unit between May 2022 and October 2022. Patients were distributed into intervention groups that utilized cryotherapy with ice gloves and ice boots and control groups that did not receive cryotherapy. Patient self-report questionnaires were used to quantify patients' symptoms and QoL after treatment. The intervention group exhibited significantly less cold sensitivity, hand and foot numbness, and hand tingling than the control group. Daily CIPN symptoms were substantially milder in the intervention group. Before and after treatment, nerve pain, balance, and muscle and joint discomfort were similar. Intervention and control groups have varied neurotoxicity adverse reaction scores. 2.4% of controls had grade 4 motor neurotoxicity impairment. Physical function and QoL improved in the intervention group. Cryotherapy relieves CIPN symptoms in breast cancer patients receiving carboplatin and paclitaxel chemotherapy. More thorough trials should be carried out to determine the best time limit and duration of cryotherapy.

ID: 200950 Differential Targeted Multiplexed, High-Frequency and Conventional Spinal Cord Stimulation Reduce Streptozotocin induced Mechanical Hypersensitivity

Treatment of painful diabetic peripheral neuropathy (PDPN) patients remains a major challenge, as most pharmacological options still are unsuccessful. For these patients, spinal cord stimulation (SCS) can be a last resort treatment option. Although SCS often provides effective pain relief, a substantial number of PDPN patients do not respond to the treatment. Novel stimulation paradigms such as Differential Targeted Multiplexed (DTM) SCS are suggested to further improve the efficacy of SCS on pain relief and increase responder rates. DTM-SCS is a combination of more than one electrical field delivered with signals at different stimulation parameters (1). The aim of this study was to investigate the effects of DTM-SCS on pain relief in an animal model for PDPN and compare this to Sham-SCS, conventional (Con-) SCS and High frequency (HF-) SCS.

Vitamin B12 Deficiency and Peripheral Neuropathy in patients with Type 2 Diabetes Mellitus Treated with Metformin. An integrative review

Background/Purpose: Type 2 diabetes mellitus (T2DM) is a worldwide pathology with several complications, and 50% of patients with T2DM develop peripheral neuropathy (PN) in the long term. The present study aimed to review the literature on the association between PN and vitamin B12 deficiency in patients with T2DM treated with metformin. Materials and methods: A literature review was carried out in the PubMed Central, Cochrane, Scielo, Scopus and Embase databases, from 2015 to 2021. We found 755 studies, of which 16 were included. Results: The serum level of vitamin B12 was lower in individuals with at least one neurological symptom. Treatment with metformin was associated with reduced serum vitamin B12 levels, and its use was defined as a probable cause of PN due to reduced vitamin B12. Studies that performed supplementation with methylcobalamin demonstrated significant improvement in neuropathic symptoms. Vitamin B12 supplementation therapy for diabetic patients undergoing metformin treatment has been suggested. Conclusion: Deficiency of vitamin B12 associated to metformin can be considered a risk factor for PN. Periodically evaluation of serum levels of vitamin B12 is recommended for patients on metformin treatment.

Bariatric surgery shown to reverse diabetes related neuropathic complications among people with obesity

Bariatric surgery is increasingly been utilized to induce and maintain significant weight loss among patients with obesity. For patients with diabetes, bariatric surgery is associated with increased likelihood of reversal of type 2 diabetes; however, its impact on long-term diabetes related neuropathic complications remain unclear. This is particularly relevant given the potential increased risk of “treatment-induced neuropathy” associated with rapid improvements of glucose control. A study undertaken by research team from the University of Michigan have now reported that bariatric surgery may improve neuropathy by regenerating damaged nerves. In the study published in the journal Diabetologia, 120 patients who underwent bariatric surgery for obesity were followed up for over 2 years after the procedure. Metabolic risk factors such as high glucose, high blood pressure and lipid levels were significantly improved. The researchers also assessed two primary measures for peripheral neuropathy in patients with obesity by undertaking skin biopsies to assess nerve fibre density in the thigh and the leg. They observed that 2 years after bariatric surgery, nerve fibre density improved in the thigh and remained stable in the leg. This is particularly relevant given that the natural history of peripheral neuropathy among patients with obesity is often associated with a decline in nerve function, thus, stability in nerve fibre density is considered to be a good outcome. Furthermore, the observed improvement in nerve fibre density at the thigh indicate that bariatric surgery may be a successful therapy to improve or reverse peripheral neuropathy for patients with long-term metabolic impairment. This finding advances current therapeutic options for peripheral neuropathy, especially in patients with obesity which currently focuses on analgesia and neuropathic oral treatment such as gabapentin, amitriptyline, duloxetive, topical analgesics and non-medical treatments, like acupuncture and cognitive behavioural therapy.

Cytochrome P450 Oxidoreductase (POR) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103.

Paclitaxel is a widely used anticancer therapeutic. Peripheral neuropathy is the dose-limiting toxicity and negatively impacts quality of life. Rare germline gene markers were evaluated for predicting severe taxane-induced peripheral neuropathy (TIPN) in the patients of European ancestry. In addition, the impact of Cytochrome P450 (CYP) 2C8, CYP3A4, and CYP3A5 metabolizer status on likelihood of severe TIPN was also assessed. Whole-exome sequencing analyses were performed in 340 patients of European ancestry who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Patients who experienced grade 3-4 (n = 168) TIPN were compared to controls (n = 172) who did not experience TIPN. For the analyses, rare variants with a minor allele frequency ≤ 3% and predicted to be deleterious by protein prediction programs were retained. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of severe TIPN. CYP star alleles for CYP2C8, CYP3A4, and CYP3A5 were called. An additive logistic regression model was performed to test the association of CYP2C8, CYP3A4, and CYP3A5 metabolizer status with severe TIPN. Cytochrome P450 oxidoreductase (POR) was significantly associated with severe TIPN (P value = 1.8 ×10-6). Six variants were predicted to be deleterious in POR. There were no associations between CYP2C8, CYP3A4, or CYP3A5 metabolizer status with severe TIPN. Rare variants in POR predict an increased risk of severe TIPN in patients of European ancestry who receive paclitaxel.

The Relationship between Hba1c Levels and Body Mass Index with Severity of Diabetic Neuropathy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Introduction: Diabetic neuropathy is the most common microvascular complication in diabetes mellitus patients. Diabetic neuropathy is known to be associated with conditions of hyperglycemia and obesity that occur in diabetic patients. Hyperglycemia in diabetic patients can be monitored through HbA1c levels. This study aimed to assess the relationship between HbA1C values and body mass index with the severity of diabetic neuropathy based on nerve conduction velocity examination.&#x0D; Methods: A study with a cross-sectional design with a total of 25 subjects with diabetes mellitus. The severity of diabetic neuropathy was determined based on Baba's diabetic neuropathy classification (BDC), degrees 0 to 4. In all study subjects, plasma HbA1c levels were examined, and body mass index was assessed. The relationship between categorical variables was tested with the chi-square test, and the relationship between numerical and categorical variables with a one-way ANOVA test, the value was considered statistically significant if the p-value &lt;0.05.&#x0D; Results: The 25 subjects with diabetes found a mean age of 54.88 (±SD 8.918) years, with a gender distribution of 46.4% for women and 42.9% for men. The average HbA1c level was 8.9560 (± 2.21850), and the highest body mass index was obese (50%). There was a significant relationship between HbA1c levels and the severity of diabetic neuropathy based on electrophysiological examination (p&lt;0.05), but there was no significant relationship between the value of body mass index and the severity of diabetic neuropathy.&#x0D; Conclusion: Increased HbA1c levels are associated with increased severity of peripheral neuropathy in patients with diabetes mellitus.

Effects of Motor Rehabilitation on Balance and Functional Activities in Elderly Patients with Peripheral Neuropathy and Recurrent Falls.

To date, little is known about the effects of motor rehabilitation in peripheral neuropathy (PN) patients with a history of recurrent falls (RFH). This study aimed to assess balance and the activities of daily living (ADLs) in elderly lower limb PN patients with and without RFH and to verify the effects of motor rehabilitation on balance and ADLs in these patients. We collected data from 64 lower limb PN patients, who underwent a conventional motor rehabilitation program: 35 patients had a history of recurrent falls, and 29 did not. The Berg Balance Scale (BBS) and motor FIM, before and after rehabilitation, were the outcome measures. After rehabilitation, lower limb PN patients with RFH had significantly higher scores in BBS and motor FIM (p < 0.001, for both) than at entry. The final BBS score and effectiveness in the BBS score of lower limb PN patients with RFH were lower than those of patients without RFH (p < 0.05 and p = 0.009, respectively). The study shows that conventional motor rehabilitation improves both balance and ADLs in patients, but balance improvement is lower in those with RFH. Thus, motor rehabilitation can be a therapeutic option for the management of these patients.

A randomized controlled trial of hand/foot-cooling by hilotherapy to prevent oxaliplatin-related peripheral neuropathy in patients with malignancies of the digestive system

Both acute and chronic symptoms of oxaliplatin-induced peripheral neuropathy (OIPN) affect patients' treatment dose and duration as well as quality-of-life. Hand/foot-cooling has been shown to reduce taxane-induced peripheral neuropathy but there is unclear evidence in the setting of oxaliplatin. In a monocentric, open-label phase II trial, patients with malignancies of the digestive system receiving oxaliplatin-based chemotherapy were randomly assigned to receive either continuous cooling of hands and feet using hilotherapy at 11°C during oxaliplatin infusion compared with usual care (no cooling). The primary endpoint was grade ≥2 neuropathy-free rate in 12 weeks after initiation of chemotherapy. Secondary endpoints included OIPN-related treatment alterations, acute OIPN symptoms and perceived comfort of the intervention. The intention-to-treat population included 39 patients in the hilotherapy group and 38 in the control group. The grade ≥2 neuropathy-free rate at 12 weeks was 100% in the experimental group versus 80.5% in the control group (P= 0.006). This effect was persistent at 24 weeks (66.0% versus 49.2%, respectively) (P= 0.039). Next, treatment alterations-free rate at week 12 was 93.5% in the hilotherapy group compared with 83.3% in the control group (P= 0.131). Patients in the hilotherapy group experienced significantly less acute OIPN symptoms of numbness or tingling [odds ratio (OR) 0.05, 95% confidence interval (CI) 0.02-0.11, P < 0.0001], pain (OR 0.06, 95% CI 0.02-0.15, P < 0.0001) and/or cold sensitivity (OR 0.02, 95% CI 0.01-0.05, P < 0.0001) in fingers or toes as well as less pharyngeal cold sensitivity (OR 0.14, 95% CI 0.05-0.42, P= 0.0005). The majority of patients in the hilotherapy group rated the intervention as neutral, rather comfortable or very comfortable. In this first study on hand/foot-cooling in oxaliplatin alone, hilotherapy significantly reduced the incidence of grade ≥2 OIPN at 12 and 24 weeks. Hilotherapy also reduced acute OIPN symptoms and was generally well tolerated.

Short-term evaluation of motor and sensory nerve conduction parameters in COVID-19-associated peripheral neuropathy patients

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) is mostly associated with upper and lower respiratory tract manifestations. However, coronavirus disease 19 (COVID-19) can result in a wide range of other systemic symptomatology, including neuropsychiatric, psychological, and psychosocial impairments. Literature regarding neurological compromise, including neuropathy and sensory and motor affection associated with COVID-19, is still limited.This study aims to evaluate the sensory, motor neuropathy, and secondary neurological impairment among patients with mild to moderate coronavirus disease associated with peripheral neuropathy within 1 month.MethodsForty participants, including 20 mild to moderate COVID-19 patients with peripheral neuropathy and 20 age and gender-matched healthy volunteers, were recruited in this case/control study. Laboratory evaluation focused on C-reactive protein (CRP) and D-dimer levels. Oxygen saturation for all participants was recorded. The neurophysiological study included motor nerve study, sensory nerve study, and F wave study for upper and lower limbs were done.ResultsThe two groups were similar regarding baseline data. Neurological symptoms’ onset in the COVID-19 group ranged from 4 to 24 days. Levels of CRP and D-dimer levels were significantly higher in patients versus the control group. Motor nerve conduction (MNC) amplitude and latency for the median nerve were significantly compromised among the COVID-19 group. The MNC latency and F wave latency for the posterior tibial nerve were significantly higher in the COVID-19 group. The CRP and D-dimer levels were associated with a significant positive correlation with a latency of median nerve MNC, sensory nerve conduction (SNC), and f-wave; latency of MNC and F wave of the posterior tibial nerve; and SNC latency for sural nerve.Conclusionneurological involvement can occur in mild to moderate cases of SARS-COV-2 infection and add to the burden of the disease. Neurological symptoms in the course of COVID-19 disease should be interpreted cautiously, and appropriate diagnosis, including nerve conduction studies and management, should be considered.Trial registrationClinicalTrials.gov. NCT05721040.

Abstract P4-04-01: Safety and efficacy of cryotherapy in the prevention and treatment of chemotherapy-induced peripheral neuropathy in breast cancer patients

Abstract Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem that can be caused by some cytotoxic agents used in breast cancer (BC) treatment, most commonly seen following taxane-based therapy[1,2]. Several strategies have been studied for CIPN prevention and treatment, but, still, there is no standard recommendation, options are limited and results unsatisfactory [1]. Cryotherapy is a technique that consists of reducing the blood flow in a certain area of the body by cold temperatures, in order to limit the cytotoxic reach. A few studies have been conducted to analyze the safety and efficacy of this strategy in CIPN prevention and treatment, and results are controversial [3,4,5]. More data is needed to clarify cryotherapy role in this clinical context. Methods This is a retrospective analysis of 40 BC patients treated at a single Brazilian institution between December 2019 and June 2022, aiming at efficacy and safety of cryotherapy in the prevention and treatment of CIPN. Cryotherapy was administered by the Hilotherm Clinic Chemo HT02 device (Hilotherm GmbH - Oberwil bei Zug, Switzerland [6]). The procedure consisted of patients using glove and sock-like devices on hands and feet throughout the chemotherapy infusion. The devices were pre-cooled to 10oC and then put on patients 30 minutes before starting, till one hour after the end of chemotherapy infusion. A questionnaire, as proposed by Leonard et al [7], was administered to patients every cycle to assess the development and severity of CIPN symptoms. Statistical analyses were performed by using a Cox regression model. Results Of the 40 patients analysed, 33 (83.5%) underwent a taxane-based regimen. The median number of cryotherapy sessions was three (ranging from 1 to 12), and, when excluded patients who underwent only one session of cryotherapy, the median was 4 (range 2 to 12). 75% of the 40 patients underwent cryotherapy in all chemotherapy sessions, or were still receiving chemo with cryotherapy by the time of our analysis. 80% of those who left treatment did so after the first session (HR 40.44 (CI95: 8.34 – 196.1; p&amp;lt; 0.0001). CIPN was stable or better than the baseline status for 26 (87%) of the 30 patients that underwent more than 1 session of cryotherapy; only 1 (25%) of the four patients who developed CIPN worse than the baseline status had grade 2 symptoms. Conclusion Cryotherapy is a safe and tolerable strategy that can be used during chemotherapy for breast cancer. Our data suggests that this is an efficient approach to prevent and treat CIPN, but the retrospective nature of the study and the small sample size must be considered when interpreting the results. Finally, strategies must be developed to further improve adherence and tolerability, and prospective randomized trials are needed to confirm the efficacy of cryotherapy in this context. 1. Loprinzi et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol 38:3325-3348. 2020 2. Rivera et al. Chemotherapy-Associated Peripheral Neuropathy in Patients With Early-Stage Breast Cancer: A Systematic Review. JNCI J Natl Cancer Inst, 2018, Vol. 110, No. 2 3. Rosenbaek et al. Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer. Supportive Care in Cancer (2020) 28:3763–3769 4. Ruddy et al. Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I); an ACCRU trial. The Breast Volume 48, December 2019 5. Shigematsu et al. Cryotherapy for the prevention of weekly paclitaxel-induced peripheral adverse events in breast cancer patients. Support Care Cancer. 2020 6. https://www.hilotherm.com/en/about-hilotherm/ accessed on July 15 2022 at 23:03 7. Leonard et al. Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer. BMC Cancer 2005, 5:116 Citation Format: Rafael B. Costa, Angélica Nogueira-Rodrigues, Claynner Paccely Oliveira Bessa, Rafaela Cristina Adalberto Menezes, Fernanda Coelho de Miranda Jorge Oliveira, Matheus Costa e Silva, Flávia Rocha Paes, Bruno L. Ferrari. Safety and efficacy of cryotherapy in the prevention and treatment of chemotherapy-induced peripheral neuropathy in breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-04-01.

Characteristics of Peripheral Neuropathy in Patients With Livedoid Vasculopathy

Livedoid vasculopathy (LV) is an ulcerative disorder of the lower extremities characterized by dermal vessel thrombosis with unclear cause. Recent reports of LV-associated upper extremity peripheral neuropathy and epineurial thrombosis suggest a systemic etiology for the condition. We sought to outline the characteristics of peripheral neuropathy in patients with LV. Cases of LV with concurrent peripheral neuropathy and reviewable electrodiagnostic testing reports were identified by electronic medical record database query and examined in detail. Of 53 patients with LV, 33 (62%) had peripheral neuropathy, 11 had reviewable electrodiagnostic reports, and 6 had no clear alternative explanation for neuropathy. Distal symmetric polyneuropathy was the most commonly observed pattern of neuropathy (n = 3) followed by mononeuropathy multiplex (n = 2). Most patients experienced symptoms in both upper and lower extremities (n = 4). Peripheral neuropathy is common in patients with LV. Whether this association is reflective of a systemic, prothrombotic etiology remains to be determined.

Abstract PD8-06: Incidence of Acute and Persistent Clinically Meaningful Chemotherapy Induced Peripheral Neuropathy in Patients with Early-Stage Breast Cancer Receiving Taxane Therapy: SWOG S1714 (NCT# 03939481)

Abstract Background: Taxanes play an important role in the treatment of early-stage breast cancer. Chemotherapy induced peripheral neuropathy (CIPN) is a complication of taxane therapy and can lead to treatment dose reduction or discontinuation, which may ultimately affect overall survival, and can substantially impact quality of life and functional status in survivors. The trajectory of CIPN symptoms is not well described. Methods: SWOG S1714 enrolled participants 18 years or older with Stage I-III primary non-small cell lung, primary breast, or primary ovarian/fallopian tube/peritoneal cancer starting treatment with a taxane-based regimen. Participants with baseline neuropathy were eligible to enroll. Neuropathy was assessed with the patient-reported European Organization for Research and Treatment of Cancer QLQ-CIPN20 (CIPN-20). The occurrence of clinically meaningful sensory neuropathy was defined as an increase of 8 or more points (on a 0-100 scale, with a higher score indicating more severe symptoms) between baseline and follow-up in the sensory neuropathy subscale of the CIPN-20. Assessments occurred at baseline and at 4, 8, and 12 weeks +/- 14 days and 24, 52, 104, and 156 weeks +/- 28 days after registration. Results: Among N=1336 enrolled participants, 1321 were eligible (99%). Of the eligible participants, we will report on the 1198 (90.7%) with breast cancer. The median age was 55 years (range 23-84) and 99.3% were female. The breast cancer cohort included 72.2% White, 11.7% Black, 4.9% Asian, and 11.0% Hispanic/Latino participants. Paclitaxel (every week for 12 weeks or every 2 weeks for 8 weeks) was administered to 56.2% and docetaxel (every 3 weeks for 12-18 weeks) to 43.8%. The mean baseline patient-reported CIPN-20 sensory neuropathy subscale score was 6.2 (standard deviation 12.0). Through one full year of follow up, 1084 participants (90.5%) were evaluable for sensory neuropathy at any time point. At individual assessment times, clinically meaningful sensory neuropathy was reported by 18.7% of participants at week 4, 33.0% at week 8, 46.3% at week 12, 44.8% at week 24, and 47.4% at week 52. Clinically meaningful sensory neuropathy at one or more assessments was reported by 67.8% of participants. Conclusions: In this large prospective cohort of racially/ethnically diverse participants with breast cancer receiving taxane-based therapy, 2 out of every 3 experienced clinically meaningful sensory neuropathy symptoms during the first year of treatment and nearly 50% continue to experience clinically meaningful sensory neuropathy symptoms at the end of the first year. Given the high incidence of symptoms during taxane treatment and persistence of symptoms after treatment completion, it is critical to develop effective methods to predict, prevent, and treat this toxicity. Follow up of data at 104 and 156 weeks will further characterize the trajectory of long term CIPN symptoms. Funding: NIH/NCI/NCORP grant UG1CA189974 Citation Format: Meghna S. Trivedi, Joseph M. Unger, Dawn Hershman, Amy K. Darke, Daniel L. Hertz, Thomas H. Brannagan, Stephanie J. Smith, Bryan P. Schneider, William J. Irvin Jr, Amanda R. Hathaway, Amy C. Vander Woude, Vinay K. Gudena, N. Lynn Henry, Michael J. Fisch. Incidence of Acute and Persistent Clinically Meaningful Chemotherapy Induced Peripheral Neuropathy in Patients with Early-Stage Breast Cancer Receiving Taxane Therapy: SWOG S1714 (NCT# 03939481) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-06.

Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing, China.

Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China. All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0g and >2.0g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69). In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.

Efficacy of combined application of traditional Chinese medicine foot bath and mild moxibustion in the treatment o f limb pain in diabetic peripheral neuropathy patients

Purpose: To determine the efficacy of the combination of traditional Chinese medicine (TCM) foot bath and mild moxibustion in the treatment of limb pain in patients with diabetic peripheral neuropathy (DPN).&#x0D; Methods: A total of 120 patients with symptoms of DPN-induced pain who were hospitalized at the Department of Endocrinology in the 903rd Hospital of PLA, from January 2020 to June 2021, were included in this study. They were randomly assigned to a study group and a control group, with 60 patients in each group. Patients in both groups received conventional treatments and nursing care, while those in study group were additionally treated with a combination of TCM foot bath and mild moxibustion. Treatment efficacy in the patients was evaluated using Short-Form McGill Pain Questionnaire (SF-MPQ), pain rating index (PRI), visual analogue scale (VAS), TCM symptom score (TCMSS), and Toronto Clinical Scoring System (TCSS).&#x0D; Results: Compared with control group, there were significant improvements in pain-related scores, namely, SF-MPQ, (p ˂ 0.05); PRI, (p &lt; 0.01); VAS, (p &lt; 0.05); as well as overall efficacy (p &lt; 0.05). Similar improvements were also observed with regard to TCMSS (p &lt; 0.001) and TCSS (p &lt; 0.001) in the study group. However, there were no significant changes in Adjusted Diabetes Quality of Life (A-DQOL) score and blood glucose control in both groups.&#x0D; Conclusion: Relative to the conventional treatment for DPN, limb pain and disease score of patients are significantly reduced by the combination of TCM foot bath and mild moxibustion treatments. Further clinical trials would be required prior to application in clinical practice.

Amazon Amandaba-Prevalence, Risk Factors and Self-Care Perception Associated with Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: A Cross-Sectional Study.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of type 2 diabetes mellitus. There is a gradual loss of protective sensation in the skin and the function of the foot joints, increasing the risk of injury as the disease progresses. The objective of this study was to verify whether socioeconomic factors, health risk factors, and self-care are associated with DPN. Observational cross-sectional with 228 individuals of ≥30 years in Family Health Strategies in a city in the eastern Amazon, in northern Brazil, using questionnaires containing socioeconomic information, clinical and laboratory parameters, the Summary of Diabetes Self-Care Activities Questionnaire, and the Michigan Neuropathy Screening Instrument. The prevalence of DPN was 66.6%. The presence of neuropathy is associated with male gender, dyslipidemia, and increased microalbuminuria. Logistic regression analysis revealed male subjects' increased BMI and altered HDL levels were associated with DPN. In men with altered BMI, and dysregulation in biochemical parameters, neuropathy is more prevalent.

Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel

BackgroundPeripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy.ObjectiveTo compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel.MethodsThis is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome.ConclusionThis study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel.Trial registrationThe trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.

Analysis of clinical features and risk factors of peripheral neuropathy in patients with primary Sjögren's syndrome

ObjectiveTo observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS.MethodsSixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy.ResultsThe patients with PN had a longer course of disease than those without PN (z = − 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased.ConclusionPN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS.

Risk factors for taxane-induced peripheral neuropathy in patients with breast cancer.

This study investigated the clinical risk factors for peripheral neuropathy induced by docetaxel and albumin-bound paclitaxel (AP) in patients with breast cancer. This prospective observational study recruited 268 patients between March 2019 and December 2020. Patient information was obtained through the query system for laboratory test results, patient consultations, and scale evaluations. Neuropathic symptoms were followed up throughout and until 3 months after taxane chemotherapy. Univariate and multivariate analyses were used to find the risk factors for overall and moderate-severe taxane-induced peripheral neuropathy (TIPN). Cumulative dose (odds ratio [OR] = 3.533, 95% confidence interval [CI]: 1.797-6.944, p < 0.001), body mass index (BMI) (OR = 2.926, 95% CI: 1.621-5.281, p < 0.001), body surface area (BSA) (OR = 1.724, 95% CI: 1.011-2.941, p = 0.045), and hypocalcemia (OR = 4.899, 95% CI: 1.518-15.811, p = 0.008) all increased the risk of TIPN. Only cumulative dose (OR = 2.577, 95% CI: 1.161-5.719, p = 0.020) and BSA (OR = 2.040, 95% CI: 1.073-3.877, p = 0.030) were independent risk factors for moderate-severe TIPN. Cumulative dose, BMI, BSA, and hypocalcemia are all risk factors for overall TIPN, whereas cumulative dose and BSA are risk factors for moderate-severe TIPN. Patients with breast cancer who have high BMI, large BSA, hypocalcemia, and large cumulative dose may be at risk of TIPN, and intervention measures must be actively carried out for them.