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Background: Chemotherapy-induced peripheral neuropathy (CIPN) and its associated pain negatively affect patient outcomes and quality of life (QoL). The two-part MiroCIP study included interventional and prospective observational studies. Here, we report the latter, describing CIPN incidence, risk factors, and outcomes. Research design and methods: This 1-year, multicenter, prospective registry study (May 2021–April 2023) included patients aged ≥ 20 years with colorectal, gastric, non-small cell lung, or breast cancer who were scheduled to undergo chemotherapy with oxaliplatin or taxane. The primary endpoint was Grade ≥ 2 sensory CIPN incidence within 12 months after chemotherapy initiation. Subjective and objective symptoms, QoL, and pain were evaluated. Results: Overall, 216 patients (female, 64.4%; mean age, 60.3 years) were included. Ninety-one (42.1%) and 131 (60.6%) patients received oxaliplatin- and taxane-based chemotherapy, respectively (six received both and were included in both groups). Grade ≥ 2 CIPN occurred in 96 patients (44.4%; 72.8/100 person-years), with 70.8% (68/96 patients) developing symptoms within 90 days. The most prominent CIPN symptoms were limb numbness/tingling and decreased vibration sensibility. No clinically meaningful risk factors were identified. Conclusions: We clarified CIPN incidence in cancer patients. Subjective symptoms (limb numbness/tingling, decreased vibration sensibility) and pain are important CIPN symptoms requiring careful monitoring. Trial registration: jRCTs031210101. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy. The objective of this prospective observational study was to examine the association between circadian misalignment (CM), as measured by phase angle difference (PAD) of biological and behavioral rhythms and CIPN. The PAD of cortisol acrophase and actigraphy-based sleep end time in breast cancer patients was measured and categorized into low PAD (n = 11) and high PAD (n = 12) groups based on median value. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN20 (CIPN20). The assessment of CM revealed that the sleep end time of the low PAD group was more delayed in relation to cortisol acrophase compared to the high PAD group. The low PAD group demonstrated significantly higher CIPN20 global and sensory scale scores compared to the high-PAD group at one month post-chemotherapy, with an estimated group difference of 17.63 ± 4.75 and 27.07 ± 6.70 (p = 0.001 and p < 0.001, respectively). The present findings indicate that the low PAD group, which exhibited a relatively delayed behavioral rhythm with respect to its biological rhythm, displayed an increased susceptibility to CIPN. Further large-sample research is necessary to attain a comprehensive understanding of the mechanisms through which CM affects CIPN. [ABSTRACT FROM AUTHOR]

Simple Summary: The management of neuropathic pain in cancer patients remains a challenge, particularly in children and adolescents. The subjectivity of pain, the limited approved drugs, the scarcity of clinical trials, and the lack of guidelines are the most relevant difficulties in assessing, evaluating, and managing neuropathic pain in children. Neuropathic pain (NP) is a common complication associated with some types of childhood cancer, mainly due to nerve compression, chronic post-surgical pain, chemotherapy, and radiotherapy. NP is usually less responsive to traditional analgesics, and there is generally a lack of evidence on its management in cancer patients, leading to recommendations often based on clinical trials conducted on other forms of non-malignant NP. In pediatric oncology, managing NP is still very challenging for physicians. Different factors contribute to increasing the risk of undertreatment: (a) children may be unable to describe the quality of pain; therefore, the risk for NP to be underestimated or remain unrecognized; (b) specific tools to diagnose NP have not been validated in children; (c) there is a lack of randomized clinical trials involving children, with most evidence being based on case series and case reports; (d) most drugs used for adult patients are not approved for childhood cancers, and drug regulation varies among different countries; (e) recommendations for pediatric pain treatment are still not available. In this paper, a multidisciplinary team will review the current literature regarding children with cancer-related NP to define the best possible diagnostic strategies (e.g., clinical and instrumental tests) and propose a therapeutic care pathway, including both non-pharmacological and pharmacological approaches, which could help pediatricians, oncologists, neurologists, and pain therapists in designing the most effective multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating toxicity of many drugs used in cancer treatment. There are numerous available strategies for preventing or treating CIPN, but few are guideline-recommended, due to limited evidence of their effectiveness. The primary objective of this survey was to understand what strategies patients used to prevent or treat CIPN, and to understand their perceptions around CIPN prevention and treatment. Methods: The Multinational Association of Supportive Care in Cancer (MASCC) Neurological Complications Study Group created a cross-sectional online survey to recruit individuals who are currently or had previously received neurotoxic chemotherapy treatment and self-reported peripheral neuropathy. Descriptive statistics were reported. Results: Most of the 447 survey participants did not use any CIPN prevention strategy (71%), though given options of any strategy the plurality preferred a prescribed medication or supplement (30%). The most common treatment strategy used was exercise (47%), with some patients trying prescription medications including non-guideline recommended gabapentin (33%) or guideline-recommended duloxetine (8%) options. Nearly half of participants (49%) used at least one non-prescribed medication for treating CIPN. Patients often followed suggestions of their medical oncology clinical team, but sometimes relied on the internet or other patients to recommend non-prescription strategies. Conclusion: In the absence of many guideline-recommended strategies for CIPN prevention and treatment, some patients use options with minimal evidence of effectiveness. Additional research is needed to determine which strategies are effective for prevention and treatment so these can be implemented in practice to improve treatment outcomes in patients with cancer. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral neuropathy (PN) is the most common neurodegenerative disorder, and the primary causes are chemotherapy-induced peripheral neuropathy (CIPN) and diabetic neuropathy (DN). Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-pharmacological and non-invasive intervention that targets key pathways involved with PN. However, research is needed to determine the feasibility, acceptability, and effects of taVNS in people with PN. It is also critical that this research on taVNS include the perspectives of Black and Hispanic/Latino patients, who are often underrepresented in research. Methods: This research was comprised of two consecutive studies: a survey and a pilot randomized sham-controlled trial (RCT). The survey assessed symptom burden, management strategies, and interest in taVNS among CIPN patients. The pilot RCT evaluated the feasibility, acceptability, and preliminary effects of taVNS in Black and Hispanic/Latino patients with CIPN or diabetic neuropathy. Participants were recruited from the University of Miami medical system, with culturally sensitive approaches to enhance minority participation. Results: The survey included 62 respondents, 78% Black or Hispanic/Latino, revealing high symptom burden and significant interest in taVNS (82% expressed moderate to high interest). The pilot RCT enrolled 28 participants, achieving a 42% recruitment rate and 86% retention. taVNS was well tolerated, with no significant adverse effects. Preliminary data indicated a decrease in neuropathic symptoms and an increased heart rate variability (HRV) during active taVNS, suggesting autonomic modulation. Tingling sensation and pain decreased by median values of 2.0 and 1.5, respectively. Additionally, the median values for standard deviation of the RR interval increased from 34.9 (CI = 21.6–44.8) at baseline to 44.8 (CI = 26.5–50.3) during intervention. Exit interviews highlighted positive participant experiences and identified potential barriers, such as protocol length and distrust in medical research. Conclusion: The findings underscore the need for novel CIPN treatments and demonstrate the feasibility of conducting taVNS research in historically underrepresented populations. High interest in taVNS and successful recruitment and retention rates suggest that culturally sensitive approaches can enhance minority participation in clinical trials. These findings will be used to develop a large clinical trial to determine the efficacy of repeated taVNS in a diverse cohort. Clinical Trial Registration: https://clinicaltrials.gov , identifier (NCT05896202). [ABSTRACT FROM AUTHOR]

Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects. We postulated that inhibition of GABA's degradation enzyme, GABA aminotransferase (GABA-AT), would increase endogenous GABA levels and produce analgesia. We evaluated antinociceptive efficacy of the potent GABA-AT inhibitor OV329 in rodent models of neuropathic and inflammatory pain and assessed possible side effects (i.e., reward and motor impairment). OV329 attenuated the development and maintenance of mechanical and cold hypersensitivities induced by the chemotherapeutic agent paclitaxel. Prophylactic OV329, administered systemically, normalized paclitaxel-induced increases in glutamate levels and suppressed neuropathic nociception. Intrathecal OV329 suppressed paclitaxel-induced mechanical hypersensitivity, elevating GABA, and reducing glutamate levels in the lumbar spinal cord, consistent with a spinal site of action. Furthermore, OV329 largely synergized with paclitaxel to enhance 4T1 tumor cell line cytotoxicity without altering viability of nontumor cells. OV329 also attenuated inflammation-induced mechanical hypersensitivity induced by intraplanar injection of complete Freund's adjuvant (CFA) with efficacy comparable to morphine. Unlike morphine, OV329 did not produce reward in a conditioned place preference assay in mice and was not self-administered intravenously by rats. Antinociceptive efficacy of OV329 was observed at doses that did not impair motor function or produce tolerance following chronic dosing. Thus, inhibition of GABA-AT with OV329 represents a unique therapeutic strategy to alleviate neuropathic and inflammatory pain with no apparent abuse liability, potentially producing a beneficial spectrum of pharmacological effects through enzymatic regulation. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical relevance and assay sensitivity of using personalized outcomes using data from a randomized clinical trial (RCT) in people with chemotherapy-induced peripheral neuropathy (CIPN). Design This study is a secondary analysis that leveraged data from a RCT of transcutaneous electrical stimulation for CIPN to test whether personalized outcomes could minimize potential floor effects and increase the assay sensitivity of pain clinical trials (ie, ability to detect a true treatment effect). Setting Participants were recruited for a RCT from community oncology clinics in the United States. Participants Adults with CIPN (N  = 72) who reported on average ≥4 intensity (measured via a 7-day baseline diary) for at least 1 of the following pain qualities: hot/burning pain, sharp/shooting pain, and/or cramping. Methods Personalized outcomes were defined based on participants' unique presentation of pain qualities at baseline, measured via 0-10 numeric rating scales (NRS), or ranking of the distress caused by the pain qualities. Analysis of covariance models estimated the treatment effect as measured by personalized and non-personalized outcomes. Results The adjusted mean difference between groups was higher using personalized outcomes (ie, 1.21-1.25 NRS points) compared to a non-personalized outcome (ie, 0.97 NRS points), although the standardized effect sizes were similar between outcomes (0.49-0.54). Conclusions These results suggest that personalized pain quality outcomes could minimize floor effects, while providing similar assay sensitivity to non-personalized pain quality outcomes. Personalized outcomes better reflect an individual's unique experience, inherently providing more clinically relevant estimates of treatment effects. Personalized outcomes may be advantageous, particularly for clinical trials in populations with high inter-individual variability in pain qualities. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chemotherapy‐induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient‐reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision‐making. Methods: Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE), Total Neuropathy Scale–clinical version (TNSc) items, and the disease‐specific quality of life ‐ Chemotherapy‐Induced Peripheral Neuropathy questionnaire (QLQ‐CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k‐means clustering and internally validated by discriminant functional analysis. Results: Both NCI‐CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ‐CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ‐CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ‐CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. Conclusions: Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well‐differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ‐CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation. [ABSTRACT FROM AUTHOR]

Aim: Chemotherapy‐induced peripheral neuropathy (CIPN) is a major toxicity limiting the use of nab‐paclitaxel (Nab‐P) in treating patients with pancreatic cancer. The aim of this study was to identify the factors affecting CIPN using patient‐reported outcome measures and the minimally invasive volumetric absorptive microsampling (VAMS) technique. Methods: The maximum concentrations of paclitaxel (Cmax) were measured from 81 VAMS samples collected from 44 participants with pancreatic cancer. The association between CIPN development and demographic, clinical and pharmacokinetic factors was determined using univariable and multivariable logistic regression. The association between CIPN severity and the factors was evaluated using Spearman's rank correlation. The impact of Cmax and the number of treatment cycles on the severity was assessed using multivariable linear regression. Results: The development of CIPN was significantly associated with cumulative dose (odds ratio 1.005, 95% confidence interval [CI] 1.003‐1.007), treatment cycles (3.47, 2.25‐5.85), alkaline phosphate (0.992, 0.985‐0.998) and age (1.092, 1.020‐1.179), with an area under the receiver operating characteristic curve of 0.89 (95% CI 0.83‐0.95). The severity of CIPN significantly worsened with increasing cumulative dose (coefficient 0.58, 95% CI 0.44‐0.69), treatment cycles (0.57, 0.44‐0.68) and age (0.18, 0.00‐0.35). The severity of CIPN was predictable from treatment cycles (P =.0002) and Cmax (P =.01). Conclusion: The higher the cumulative dose of Nab‐P, treatment cycles and age, the more frequently and severely do the patients experience CIPN. In predicting the severity of CIPN using Cmax, minimally invasive VAMS is a feasible alternative to venous blood sampling. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness of a 13-week combined supervised and home-based exercise program in alleviating the symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in patients with breast cancer (BC). Methods: In this non-randomized controlled study, 77 patients with BC selected after applying the inclusion and exclusion criteria were allocated to the intervention (n = 37) or control (n = 40) group. Patients in the intervention group underwent a 13-week exercise program consisting of health education and hand and foot exercises combined with aerobic, resistance, and balance training, while those in the control group received usual care. The symptoms of CIPN were assessed at baseline (T0), post-intervention (T1), and 3 months post-intervention (T2). Physical fitness and finger flexibility were assessed at T0 and T1. A generalized estimating equation (GEE) model was used to analyze the repeated measures data. Results: The results of GEE showed a significant group effect, indicating significant intergroup differences in the total CIPN score and the dimensions of occurrence, severity, disruption, and frequency (all P < 0.05). Moreover, the two groups showed significant differences in finger flexibility and balance at T1 (all P < 0.05). Conclusions: The exercise program was effective in alleviating the symptoms of CIPN and improved balance and finger dexterity in comparison with the control group. Randomized controlled trials with larger sizes are required to validate these findings. [ABSTRACT FROM AUTHOR]

Purpose of review: Advances in oncological therapies have resulted in an increase in the number of patients living with and beyond cancer. The personal and societal impact of chronic pain in the survivor population represents an area of significant unmet need. Capsaicin (a TRPV1 agonist) may provide analgesia with limited systemic side effects. This review looks to summarise the most recent evidence regarding the use of capsaicin in the management of cancer pain. Recent findings: Various international guidelines have recently endorsed the use of high concentration capsaicin patches in the treatment of chronic painful chemotherapy induced peripheral neuropathy. Numerous studies support the use of capsaicin in the treatment of peripheral neuropathic pain. This promising data is predominantly yielded from pain secondary to herpes zoster and diabetic neuropathy, with an expanding but small evidence base for its utility in other neuropathic pains. Emerging data suggests that treatments are better tolerated and provide analgesia more rapidly when compared with systemic treatments. Summary: Whilst randomised controlled trial data in the treatment of cancer pain are lacking, recent large cohort studies, and international guidelines, support the use of high concentration capsaicin patches in a wide variety of neuropathic pain secondary to cancer treatments. [ABSTRACT FROM AUTHOR]

Objectives: Chemotherapy-induced peripheral neuropathy (CIPN), a frequently occurring adverse event associated with paclitaxel/carboplatin (TC) combination therapy, causes limb pain and markedly reduces the patient’s quality of life. Since zinc has been reported to be associated with neuropathic pain, we investigated the relationship between CIPN due to TC therapy and serum zinc levels. Methods: The study included 13 patients with gynecological cancer whose serum zinc levels were measured before and during TC therapy. CIPN was classified into severity grades based on the Common Terminology Criteria for Adverse Events v5.0. A retrospective analysis was conducted on the relationship between the serum zinc level before TC therapy (PreZn), the minimum serum zinc level measured during TC therapy (MinZn), the MinZn/PreZn ratio, the number of TC treatment cycles, and the maximum grade of CIPN (MaxG) using Pearson’s correlation coefficient. Moreover, an analysis was also conducted on clinical factors influencing MaxG, as well as fluctuations in serum zinc levels and CIPN grades for each cycle of TC therapy. Results: A negative correlation was observed between the MinZn/PreZn ratio and MaxG (r=–0.557, p=0.048). The clinical factors influencing CIPN remained unclear, and the decrease in serum zinc levels and the aggravation of CIPN plateaued after the third cycle. Conclusions: If a decrease in serum zinc levels during TC therapy is smaller than before therapy, it may imply the existence of a causal relationship that suppresses the aggravation of CIPN.

Yongming Xu,1,&ast; Junzhen Wu,1,&ast; Qingqing Jiang,2 Yingying Lv,1 Jin Zhou,1 Zhiyu Wang,3 Hui Zhao,3 Dongping Du1 1Department of Pain Management Center, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Internal Oncology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongping Du, Department of Pain Management Center, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China, Tel +86-21-24058896, Email dudp@sjtu.edu.cn Hui Zhao, Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86-21-24058328, Fax +86-21-240598328, Email zhao-hui@sjtu.edu.cnObjective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy and it is currently intractable We compared the efficacy of transcutaneous electrical acupoint stimulation (TEAS) against non-TEAS groups and investigated the variables that predict effective relief of upper extremity pain in cancer survivors with CIPN.Methods: We retrospectively collected data of cancer survivors who developed CIPN between May 2017 to March 2022. All eligible CIPN patients were divided into TEAS group (received TEAS) and non-TEAS group (did not receive TEAS) in our department. A 1:1 ratio propensity score matching (PSM) was used to balance the baseline features. The change of numerical rating scale (NRS), Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and sympathetic skin response (SSR) parameters are all assessed after treatment. The procedure was considered a clinically effective relief if the patients’ NRS scores were reduced by 50% or more, and overall patients with effective relief were all counted after treatment. Furthermore, a multivariable logistic regression model was utilized to evaluate the predictors of effective relief following CIPN treatment.Results: : A total of 102 cancer survivors with CIPN were analyzed after PSM (51 in each group). The change of NRS, SF-MPQ-2, SSR latency and SSR amplitude in TEAS group were significantly higher than those in non-TEAS group at 3 weeks after therapy (all P< 0.01). In addition, the effective relief rate was significantly higher in TEAS group than in non-TEAS group (P=0.026). Multivariate logistic regression on the total study cohort showed that TEAS group (OR 2.783, P = 0.025) and the baseline SSR amplitude of the upper extremity < 1265 μV (OR 12.191, P = 0.000) were independent predictive factors for the clinical efficacy.Conclusions: : TEAS significantly decreased the severity of CIPN. TEAS group and baseline SSR amplitude of the upper extremity < 1265 μV were the independent predictive factors for the clinical efficacy after treatment.Keywords: transcutaneous electrical acupoint stimulation, chemotherapy-induced peripheral neuropathy, sympathetic skin response, cancer survivors, neuropathic pain

Yeeun Kim,1,2,&ast; Min-A Je,1,2,&ast; Myeongguk Jeong,1,2 Hyeokjin Kwon,1,2 Aelee Jang,3 Jungho Kim,1,2 Go-Eun Choi1,2 1Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea; 2Next-Generation Industrial Field-Based Specialist Program for Molecular Diagnostics, Brain Busan 21 Plus Project, Graduate School, Catholic University of Pusan, Busan, 46252, Republic of Korea; 3Department of Nursing, University of Ulsan, Ulsan, 44610, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Go-Eun Choi; Jungho Kim, Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea, Tel +82-51-510-0563 ; +82-51-510-0660, Fax +82-51-510-0568, Email gechoi@cup.ac.kr; jutosa70@cup.ac.krBackground: Paclitaxel (PTX) can induce chemotherapy-induced peripheral neuropathy (CIPN) as a side effect. The aim of this study was to understand the neurochemical changes induced by NGF/TrkA signaling in PTX-induced neuropathic pain.Methods: The PTX-induced CIPN mouse model was evaluated using nerve conduction velocity (NCV) and behavioral tests. Protein expression in mouse DRG was observed by Western blotting and immunohistochemistry. Nerve growth factor (NGF), IL-6, and IL-1β mRNA levels were determined using qRT-PCR by isolating total RNA from whole blood.Results: PTX showed low amplitude and high latency values in NCV in mice, and induced cold allodynia and thermal hyperalgesia in behavioral assessment. Activating transcription factor 3 (ATF3) and MAPK pathway related proteins (ERK1/2), tropomyosin receptor kinase A (TrkA), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) were upregulated 7th and 14th days after 2 mg/kg and 10 mg/kg of PTX administration. Protein kinase C (PKC) was upregulated 7th days after 10 mg/kg PTX treatment and 14th days after 2 mg/kg and 10 mg/kg PTX administration. NGF, IL-6, and IL-1β fold change values also showed a time- and dose-dependent increase.Conclusion: Taken together, our findings may improve our understanding of the nociceptive symptoms associated with PTX-induced neuropathic pain and lead to the development of new treatments for peripheral neuropathy.Keywords: Chemotherapy-induced peripheral neuropathy, paclitaxel, nerve growth factor, tropomyosin receptor kinase A, transient receptor potential vanilloid 1

Abstract 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

Background: The efficacy and acupoint selection of acupuncture in treating chemotherapy-induced peripheral neuropathy (CIPN) remain controversial. This study aims to explore the specific efficacy and acupoint selection of acupuncture in treating CIPN through a meta-analysis and data mining. Methods: Searching for clinical trials on acupuncture treatment for CIPN in 8 databases, evaluating its efficacy and safety through a meta-analysis, and exploring its acupoint selection through data mining. Results: The meta-analysis included 21 studies and 2,121 patients, showing that compared with the control group, the acupuncture group could significantly improve neuropathic pain intensity (SMD = −0.66, 95% CI [−1.07, −0.25], p = 0.002), significantly reduce the NCI-CTCAE (MD = −0.29, 95%CI [−0.50, −0.08], p < 0.01), significantly reduce the FACT-NXT score (MD = 2.09, 95% CI [0.73,3.45], p < 0.05), significantly increase the motor conduction velocities (MCV) of median nerve (MD = 2.38, 95% CI [2.10, 2.67], p < 0.001), the sensory conduction velocities (SCV) of the median nerve (MD = 0.56, 95 %CI [−1.45, 2.57], p = 0.58), the SCV of the tibial nerve (MD = 1.78, 95% CI [0.50, 3.05], p < 0.01), and the SCV of sural nerves (MD = 4.60, 95% CI [0.17, 9.02], p < 0.05), as well as improving the quality of life score (MD =7.35, 95% CI [1.53, 13.18], p = 0.01). Data mining showed that the core acupoints for acupuncture treatment of CIPN were LI4, ST36, LI11, LR3, and SP6. Conclusion: Acupuncture can improve the neuropathic pain intensity, the intensity of the CIPN, MCV of the median nerve, SCV of the tibial nerve and peroneal nerve, quality of life, and has good safety in CIPN patients. LI4 (Hegu), ST36 (Zusanli), LI11 (Quchi), LR3 (Taichong), and SP6 (Sanyinjiao) are the core acupuncture points for treating CIPN, and this protocol has the potential to become a supplementary treatment for CIPN. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024551137. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical treatment of rectal cancer with a low anterior resection allows patients to maintain normal anatomy. Despite this, many patients can postoperatively develop symptoms related to bowel dysfunction known as low anterior resection syndrome (LARS). Systemic therapy for rectal cancer treatment often includes platinum-based chemotherapy agents with peripheral neuropathy as a common side effect. LARS and chemotherapy-induced peripheral neuropathy (CIPN) may greatly affect a patient's quality of life. Thus, the purpose of this study was to evaluate a potential relationship between CIPN and LARS. We found there was an association between CIPN and the development of LARS. Thus, further studies should look to evaluate the possible biological mechanisms behind this relationship. Introduction: Low anterior resection syndrome (LARS) can be a debilitating condition that develops after undergoing sphincter-preserving surgery for rectal cancer. Chemotherapy-induced peripheral neuropathy is a common side effect of platinum-based chemotherapy agents used as systemic therapy for rectal cancer treatment. The purpose of this study was to determine the potential relationship between CIPN and LARS. Methods: This was a retrospective review of patients who underwent a low anterior resection for rectal cancer and received systemic therapy contacted at least six months from the most recent surgery. Eligible patients were called and completed the relevant surveys over the phone or email. Results: There was a total of 42 patients who completed the surveys with 33 (79%) having major LARS. Presence of a diverting ileostomy was the only significantly differentcharacteristic in those with major LARS versus those without. CIPN was independently associated with LARS (p = 0.046) on linear regression when controlling for neoadjuvant chemoradiation, diverting ileostomy and tumor distance from the anal verge. Conclusions: Developing severe CIPN is associated with developing LARS. Further studies evaluating the etiology behind this relationship should be conducted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of some chemotherapeutic agents. Effective treatment is limited. OBJECTIVES: This single patient case details gua sha as an intervention to reduce CIPN. METHODS: A 38-year-old female patient received weekly treatment of gua sha in one-hour sessions for 10 weeks. The patient completed the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale to describe her CIPN throughout and postintervention. A research assistant measured the extent of numbness or tingling along the limb from baseline to 18 months after gua sha. Descriptive data were used to summarize this case. FINDINGS: After gua sha, the total FACT/GOG-NTX subscale score increased from 13 to 36, indicating a sevenfold greater change than the minimum clinically important difference. The range of limb numbness and tingling decreased, and the symptoms remained stable during follow-up. Gua sha showed a positive clinical effect. [ABSTRACT FROM AUTHOR]

• A selective agonist of GPCR LPA3 is produced by Bacillus velezensis ADS024. • Oleoyl-LPA and an extract of ADS024 promote LPA3 recruitment of 14–3-3 proteins. • ADS024 modifies cell-surface expression of LPA3 on immune cells in a MOG-EAE model. • ADS024 is efficacious in neuroinflammatory disease models of PD, HD, MS, ALS, CIPN. • Broad efficacy of ADS024 suggests a common anti-neuroinflammatory mechanism. Neuroinflammation is a common component of neurological disorders. In the gut-brain-immune axis, bacteria and their metabolites are now thought to play a role in the modulation of the nervous and immune systems which may impact neuroinflammation. In this respect, commensal bacteria of humans have recently been shown to produce metabolites that mimic endogenous G-protein coupled receptor (GPCR) ligands. To date, it has not been established whether plant commensal bacteria, which may be ingested by animals including humans, can impact the gut-brain-immune axis via GPCR agonism. We screened an isopropanol (IPA) extract of the plant commensal Bacillus velezensis ADS024, a non-engrafting live biotherapeutic product (LBP) with anti-inflammatory properties isolated from human feces, against a panel of 168 GPCRs and identified strong agonism of the lysophosphatidic acid (LPA) receptor LPA3. The ADS024 IPA extracted material (ADS024-IPA) did not agonize LPA2, and only very weakly agonized LPA1. The agonism of LPA3 was inhibited by the reversible LPA1/3 antagonist Ki16425. ADS024-IPA signaled downstream of LPA3 through G-protein-induced calcium release, recruitment of β-arrestin, and recruitment of the neurodegeneration-associated proteins 14–3-3γ, ε and ζ but did not recruit the β isoform. Since LPA3 agonism was previously indirectly implicated in the reduction of pathology in models of Parkinson's disease (PD) and multiple sclerosis (MS) by use of the nonselective antagonist Ki16425, and since we identified an LPA3-specific agonist within ADS024, we sought to examine whether LPA3 might indeed be part of a broad underlying mechanism to control neuroinflammation. We tested oral treatment of ADS024 in multiple models of neuroinflammatory diseases using three models of PD, two models of MS, and a model each of amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and chemo-induced peripheral neuropathy (CIPN). ADS024 treatment improved model-specific functional effects including improvements in motor movement, breathing and swallowing, and allodynia suggesting that ADS024 treatment impacted a universal underlying neuroinflammatory mechanism regardless of the initiating cause of disease. We used the MOG-EAE mouse model to examine early events after disease initiation and found that ADS024 attenuated the increase in circulating lymphocytes and changes in neutrophil subtypes, and ADS024 attenuated the early loss of cell-surface LPA3 receptor expression on circulating white blood cells. ADS024 efficacy was partially inhibited by Ki16425 in vivo suggesting LPA3 may be part of its mechanism. Altogether, these data suggest that ADS024 and its LPA3 agonism activity should be investigated further as a possible treatment for diseases with a neuroinflammatory component. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting side effect of chemotherapy. CIPN is difficult to grade objectively, and therefore efforts have been aimed at identifying an objective biomarker of CIPN. During the past 4 years, neurofilament light chain (NFL) has emerged as a preclinical and clinical biomarker of CIPN. Several chemotherapeutics cause rapid and dramatic increases in NFL levels in in vitro systems, rodent models, and clinical studies, which indicates that NFL reflects neuronal damage. Thus far, paclitaxel appears to cause the most pronounced increases. Early elevations in serum NFL may predict later occurrence of CIPN in cancer patients. NFL shows promise as an objective biomarker of CIPN especially in in vitro and in rodent models. The prognostic value of NFL to predict CIPN is still not established and requires prospective evaluation. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. The frequency of CIPN ranges from one in three to almost all patients depending on type of chemotherapy and dose. It causes symptoms that can range from sensitivity to touch and numbness to neuropathic pain in hands and feet. CIPN is notoriously difficult to grade objectively and has mostly relied on a clinician- or patient-based rating that is subjective and poorly reproducible. Thus, considerable effort has been aimed at identifying objective biomarkers of CIPN. Recent in vitro , animal, and clinical studies suggest that neurofilament light chain (NFL), a structural neuronal protein, may be an objective biomarker of CIPN. NFL released from cells to cell culture media reflects in vitro neurotoxicity, while NFL in serum reflects neuronal damage caused by chemotherapy in rodent models. Finally, NFL in serum may be a diagnostic biomarker of CIPN, but its prognostic ability to predict CIPN requires prospective evaluation. We discuss current limitations and future perspectives on the use of NFL as a preclinical and clinical biomarker of CIPN. [ABSTRACT FROM AUTHOR]

Purpose: To explore the reliability and validity of clinically-relevant outcome measures for balance (i.e., The Short Physical Performance Battery [SPPB] – Balance Subscale) and sensation (i.e., monofilament threshold testing) for use in clinical trials of chemotherapy-induced peripheral neuropathy (CIPN). Methods: Adult, post-treatment cancer survivors (N = 142) who had reported ≥ 4/10 CIPN symptom severity following neurotoxic chemotherapy were recruited from six National Cancer Institute Community Oncology Research Program (NCORP) sites associated with the University of Rochester Cancer Center NCORP Research Base. Participants completed the monofilament threshold test at the screening and baseline time points (i.e., one week apart), while the Quality of Life Questionnaire-CIPN20, Treatment-Induced Neuropathy Assessment Scale, and SPPB – Balance Subscale were completed at baseline. Test–retest reliability of the monofilament threshold testing scores was assessed using the Intraclass Correlation Coefficient (ICC). The convergent validity among monofilament threshold testing, SPPB – Balance Subscale, and CIPN patient-reported outcome (PRO) scores at baseline was assessed using Spearman’s correlation. Results: Ceiling effects were observed for SPPB-Balance Subscale scores as 113 (79.6%) respondents reported the highest score. Agreement between the screening and baseline monofilament threshold testing scores was moderate (ICC = 0.65). Monofilament threshold testing (rs Range: 0.14 – 0.21) and SPPB Balance Subscale scores (rs Range: -0.36 – -0.22) showed largely low correlations with all PRO measures. Conclusions: Monofilament threshold testing demonstrated moderate test–retest reliability, but low convergent validity with CIPN PROs, while the SPPB – Balance Subscale demonstrated low convergent validity with CIPN PROs and ceiling effects (i.e., highest possible score) among post-treatment cancer survivors with CIPN. Future research is needed to identify promising measures of balance and sensation loss for use in clinical trials that complement CIPN PROs to aid in the identification of clinically relevant treatments for CIPN. Trial Registration: NCT04367490 [April 29, 2020]. [ABSTRACT FROM AUTHOR]

Purpose: A significant proportion of cancer patients suffer from chemotherapy-induced peripheral neuropathy (CIPN). This descriptive study aimed to examine patients' experience of CIPN symptoms, daily limitations, involvement of healthcare professionals, and social support. Methods: Cross-sectional data have been collected in the Netherlands via a national online questionnaire comprising closed items only (February 2021). Results: Out of 3752 respondents, 1975 received chemotherapy only (i.e., without targeted therapy) and were therefore included. The majority (71.2%) reported symptoms in both hands and feet (e.g., tingling and loss of sensation or diminished sensation). Participants reported most limitations in household chores, social activities, hobbies, sports, walking, and sleeping and least in family/(taking care of) children, cycling, driving, self-care, eating and drinking, and sexuality and intimacy. Many patients indicated that their healthcare professionals informed them about the possibility of CIPN development before treatment (58.4%), and they paid attention to CIPN during and after treatment (53.1%). However, many patients (43%) reported a lack of information on what to do when CIPN develops. Few participants (22%) visited their general practitioner (GP) for CIPN. In general, patients' social environments sometimes to always showed empathy to patients. Conclusions: Symptoms of CIPN are frequently reported and can result in various daily limitations. Support from professionals and peers is crucial in managing CIPN, which is sometimes lacking. Appropriate guidance and support should be provided to patients to decrease the impact of CIPN on daily life. Future research should investigate differences in chemotherapeutic agents and the resulting symptoms and consequences. [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]

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent adverse effect observed in cancer patients. This study aimed to investigate the impact of sleep phase within the biological clock on CIPN. The phase of the minimum core body temperature (CBTmin) was determined using a thermometer pill and the Munich Chronotype Questionnaire was employed to assess mid-sleep time (MSFsc), in 39 breast cancer patients. CIPN was evaluated at five time points using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale. The late sleep phase group, whose MSFsc followed CBTmin, demonstrated higher scores on the square root-transformed sensory scale than the early sleep phase group, whose MSFsc preceded CBTmin, 9-month post-chemotherapy (p=0.001). A significant between-group difference in the global and motor scale score was observed across all time points (p=0.043, 0.026, respectively). Further research using a larger sample size may contribute to elucidating the role of sleep phase in the pathogenesis of CIPN. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To explore cancer survivors' historical and current use of analgesics for chronic chemotherapy-induced peripheral neuropathy (CIPN). SAMPLE & SETTING: 142 post-treatment cancer survivors who received neurotoxic chemotherapy and were experiencing moderate to severe CIPN. METHODS & VARIABLES: Participants completed the Treatment-Induced Neuropathy Assessment Scale at baseline and reported all analgesics used to manage CIPN. Frequency of historical or current prescription analgesic use for chronic CIPN was described and stratified by CIPN pain severity. RESULTS: At baseline, 31% of participants reported historical use of analgesics for CIPN and 46% of participants were currently using analgesics for CIPN. Gabapentin was the most frequently used analgesic, historically (20%) and currently (34%), and duloxetine was used less frequently (6% historical use, 10% current use). Many participants with severe pain (59%) reported using analgesics for CIPN. IMPLICATIONS FOR NURSING: Duloxetine, the firstline treatment for chronic CIPN pain, was used less frequently than gabapentin, a common prescription analgesic for neuropathic pain. Further research is needed to determine strategies to promote the implementation of evidence-based CIPN treatments in clinical practice. [ABSTRACT FROM AUTHOR]

PROBLEM IDENTIFICATION: Chemotherapy-induced peripheral neuropathy (CIPN) can cause treatment delays or discontinuation. Exercise can improve CIPN, but the effects have been inconsistent. LITERATURE SEARCH: 12 databases and 5 websites were searched from database inception to December 22, 2023, for primary studies that were reported in English and examined the effects of exercise on CIPN in cancer survivors. DATA EVALUATION: 20 studies (N = 1,308 total participants) were identified and reviewed. SYNTHESIS: Using a random-effects model, exercise slightly improved symptoms of CIPN (Hedges's g = 0.28, Hartung-Knapp adjusted 95% confidence interval [0.12, 0.45], p = 0.002). The 95% prediction interval showed that the true effect size of future studies would likely range from -0.1 to 0.66. Frequency of performing exercise moderated the effect size, further improving symptoms. IMPLICATIONS FOR NURSING: Nurses can encourage cancer survivors to engage in exercise, such as resistance training, aerobic exercise, balance training, and/or yoga. Nurses can refer cancer survivors to trained exercise specialists or provide information about finding a community exercise program for patients with cancer. [ABSTRACT FROM AUTHOR]

Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for chemotherapy-induced peripheral neuropathy (CIPN) research, resulting in the description of numerous CIPN models constructed from human neurons. This systematic review provides a critical analysis of available models and their methodological considerations (ie, used cell type and source, CIPN induction strategy, and validation method) for prospective researchers aiming to incorporate human in vitro models of CIPN in their research. The search strategy was developed with assistance from a clinical librarian and conducted in MEDLINE (PubMed) and Embase (Ovid) on September 26,2023. Twenty-six peer-reviewed experimental studies presenting original data about human reprogrammed nonmotor neuron cell culture systems and relevant market available chemotherapeutics drugs were included. Virtually, all recent reports modeled CIPN using nociceptive dorsal root ganglion neurons. Drugs known to cause the highest incidence of CIPN were most used. Furthermore, treatment effects were almost exclusively validated by the acute effects of chemotherapeutics on neurite dynamics and cytotoxicity parameters, enabling the extrapolation of the half-maximal inhibitory concentration for the 4 most used chemotherapeutics. Overall, substantial heterogeneity was observed in the way studies applied chemotherapy and reported their findings. We therefore propose 6 suggestions to improve the clinical relevance and appropriateness of human cellular reprogramming-derived CIPN models. [ABSTRACT FROM AUTHOR]

Our purpose was to investigate the associations between falls and oxaliplatin-induced peripheral neuropathy (OIPN), sociodemographic characteristics, and clinical characteristics of older patients with colorectal cancer. The study population consisted of older adults diagnosed with colorectal cancer whose data were obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. We defined OIPN using specific (OIPN 1) and broader (OIPN 2) definitions of OIPN, based on diagnosis codes. Extensions of the Cox regression model to accommodate repeated events were used to obtain overall hazard ratios (HRs) with 95% CIs and the cumulative hazard of fall. The unadjusted risk of fall for colorectal cancer survivors with versus without OIPN 1 at 36 months of follow-up was 19.6% versus 14.3%, respectively. The association of OIPN with time to fall was moderate (for OIPN 1, HR = 1.37; 95% CI, 1.04-1.79) to small (for OIPN 2, HR = 1.24; 95% CI, 1.01-1.53). Memantine, opioids, cannabinoids, prior history of fall, female sex, advanced age and disease stage, chronic liver disease, diabetes, and chronic obstructive pulmonary disease all increased the hazard rate of falling. Incorporating fall prevention in cancer care is essential to minimize morbidity and mortality of this serious event in older survivors of colorectal cancer. [ABSTRACT FROM AUTHOR]

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is one of the commonly reported symptoms impacting cancer survivors. This study evaluated and compared the effectiveness of acupuncture treatments for CIPN.MethodsWe searched six databases from their inception to August 2024 to identify eligible randomized controlled trials (RCTs). Primary outcome were pain scores. Secondary outcomes were quality of life including FACT/GOG-Ntx and EORTC QLQ-C30. The robust error meta-regression (REMR) method was used to evaluate the dose-response relationship across treatment parameters, including number of sessions, frequency, and duration.ResultsIn total, 11 RCTs featuring 740 participants were included. The meta-analysis demonstrated that the primary analysis achieved a significant reduction in pain scores, with a standardized mean difference of [SMD= -1.23, 95% CI = (-2.22, -0.24); P < 0.01; I² = 95%], improvement quality of life including FACT/GOG-Ntx [SMD = 0.95, 95% CI = (0.02, 1.88); P < 0.01; I² = 93%] and EORTC QLQ-C30 [SMD = 0.36, 95% CI = (0.03, 0.68); P = 0.14; I² = 46%]. The nonlinear dose-response analysis suggests that pain improvement achieves the MCID at 16 treatment sessions, over 8 weeks, with a frequency of twice per week. Furthermore, analysis of the treatment duration chart shows that acupuncture maintains therapeutic effects during the follow-up period. Sensitivity analysis confirmed the robustness of these findings.ConclusionAcupuncture demonstrates significant potential in managing CIPN, particularly through individualized treatment regimens. The identified time-dose-response relationship suggests that tailoring acupuncture frequency and duration can to optimize pain relief in CIPN patients. Future high-quality studies and large-scale multicenter clinical trials are needed to validate these findings.

IntroductionPeripheral neuropathy (PN) is the most common neurodegenerative disorder, and the primary causes are chemotherapy-induced peripheral neuropathy (CIPN) and diabetic neuropathy (DN). Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-pharmacological and non-invasive intervention that targets key pathways involved with PN. However, research is needed to determine the feasibility, acceptability, and effects of taVNS in people with PN. It is also critical that this research on taVNS include the perspectives of Black and Hispanic/Latino patients, who are often underrepresented in research.MethodsThis research was comprised of two consecutive studies: a survey and a pilot randomized sham-controlled trial (RCT). The survey assessed symptom burden, management strategies, and interest in taVNS among CIPN patients. The pilot RCT evaluated the feasibility, acceptability, and preliminary effects of taVNS in Black and Hispanic/Latino patients with CIPN or diabetic neuropathy. Participants were recruited from the University of Miami medical system, with culturally sensitive approaches to enhance minority participation.ResultsThe survey included 62 respondents, 78% Black or Hispanic/Latino, revealing high symptom burden and significant interest in taVNS (82% expressed moderate to high interest). The pilot RCT enrolled 28 participants, achieving a 42% recruitment rate and 86% retention. taVNS was well tolerated, with no significant adverse effects. Preliminary data indicated a decrease in neuropathic symptoms and an increased heart rate variability (HRV) during active taVNS, suggesting autonomic modulation. Tingling sensation and pain decreased by median values of 2.0 and 1.5, respectively. Additionally, the median values for standard deviation of the RR interval increased from 34.9 (CI = 21.6–44.8) at baseline to 44.8 (CI = 26.5–50.3) during intervention. Exit interviews highlighted positive participant experiences and identified potential barriers, such as protocol length and distrust in medical research.ConclusionThe findings underscore the need for novel CIPN treatments and demonstrate the feasibility of conducting taVNS research in historically underrepresented populations. High interest in taVNS and successful recruitment and retention rates suggest that culturally sensitive approaches can enhance minority participation in clinical trials. These findings will be used to develop a large clinical trial to determine the efficacy of repeated taVNS in a diverse cohort. Clinical Trial Registrationhttps://clinicaltrials.gov, identifier (NCT05896202).

Xin-Rong Yang,1 Xin-Yi Zhang,1 Yi-Jia Xia,1 Jin Fu,1 Xiao-Xuan Lian,2 Xin-Ru Liang,2 Ying-Qi He,2 Zhuo-Hong Li1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Zhuo-Hong Li, Email lizhuohong@cdutcm.edu.cnPurpose: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment.Methods: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment.Results: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events.Conclusion: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.Keywords: huangqi guizhi wuwu decoction, chemotherapy-induced peripheral neuropathy, chemotherapy-induced peripheral neurotoxicity, Chinese medicine, meta-analysis

Abstract 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.

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]