OBJECTIVE: Common side effects of taxane chemotherapy are nail toxicity and peripheral neuropathy (CIPN) causing severe impact on the quality of life. Different methods of cryotherapy to prevent these side effects have been tested. We investigated the use of machine-controlled cooling of hands and feet to reduce nail toxicity and CIPN in patients receiving taxane chemotherapy.
METHODS: Patients receiving Docetaxel (planned dose ≥ 300 mg/m2) or Paclitaxel (planned dose ≥ 720 mg/m2 - ) in the adjuvant or palliative setting of different cancers were included. The dominant hand and foot were cooled to approximately 10 °C using the Hilotherapy machine. The contralateral hand and foot were used as intrapatient comparison. The primary endpoint was the occurrence of any CIPN due to paclitaxel or nail toxicity due to Docetaxel. Both the intention to treat population (ITT) and the per protocol population (PPP) were analyzed.
RESULTS: A total of 69 patients, 21 treated with Docetaxel and 48 with Paclitaxel, were included at our centre between 08/2020 and 08/2022. Nail toxicity due to Docetaxel was overall not significantly improved by cooling in the ITT or PPP but a significant benefit across visits was found for the ITT. CIPN due to Paclitaxel was numerically better in the ITT and significantly better in the PPP. A significant benefit of cooling on CIPN occurrence across visits was found for the ITT and the PPP. Cooling was very well tolerated.
CONCLUSIONS: Cooling of hands and feet has a clinically meaningful impact on reducing occurrence of CIPN and nail toxicity on treatment with taxanes. Effects are more significant over time and are dose dependent.
BACKGROUND: 2020-00381. Date of registration. 24th February 2020.

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history.
Plain language titleA case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaintsPlain language summaryVitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery.

OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects and main reasons for affecting quality of life and dose reduction or even discontinuation of treatment in breast cancer patients. One of the most widely prescribed chemotherapies is the \"taxanes.\" Considering that duloxetine has been used in treating neuropathies in recent years, this study aimed to investigate its effectiveness in preventing taxane-related neuropathy.
METHODS: This is a randomized controlled trial on 47 patients: 24 received a placebo and 23 received duloxetine at 30 mg daily in the first week following the injection of paclitaxel and 60 mg during the second week in each chemotherapy cycle. Patients objective (nerve conduction velocity (NCV) values) and subjective symptoms (visual analog scale including; neuropathy, paresthesia, pain, cold sensitivity, and numbness), the grades of the patients\' neuropathy (calculated according to Common Terminology Criteria for Adverse Events (CTCAE) v.5), and the presence of complications, before and after each chemotherapy cycle, were recorded.
RESULTS: The placebo group experienced significantly higher occurrences of new neuropathy (8/23 in duloxetine vs 16/24 in placebo, P = 0.029) in NCV by tibial nerve latency (- 0.28% vs 19.87%, P = 0.006), tibial amplitude (4.40% vs - 10.88%, P = 0.049), and median nerve latency (8.72% vs 31.16%, P = 0.039); administration of duloxetine significantly reduced the scores of neuropathies (P < 0.001), pain (P = 0.027), during chemotherapy, and 6 weeks later; however, no significant effect was observed on paresthesia, numbness, cold sensitivity, and other NCV measurements.
CONCLUSIONS: Paclitaxel can cause neuropathy, lasting for a long time. Our study showed duloxetine is potentially an effective medication that can prevent subjective and objective neuropathy.

BACKGROUND: Sjögren\'s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients.
METHODS: Fifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA).
RESULTS: Out of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups.
CONCLUSIONS: Our study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

OBJECTIVE: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above.
METHODS: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score.
RESULTS: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups.
CONCLUSIONS: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients\' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.

OBJECTIVE: Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis.
METHODS: One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy.
RESULTS: Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12-322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17-416.43) in psoriasis patients and 18.75 (95% CI = 1.07-327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length-dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p = .0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant.
CONCLUSIONS: Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis.

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

OBJECTIVE: The aim of this study is to determine the effect of hand-foot exercises on chemotherapy-induced peripheral neuropathy-related pain severity, falls, and quality of life in patients with colorectal cancer.
METHODS: The study was conducted in the outpatient chemotherapy unit of a public hospital between 25 April-31 December 2022. The enrolled 39 patients were randomly assigned to the intervention (n:19) and control (n:20) groups. The hand-foot exercises program was applied to the intervention group in three sessions a day and three days a week fashion for 8 weeks at home. No intervention was applied to the control group other than routine treatment and care. Data were collected through face-to-face interviews in the first interview and the 2nd, 4th, 6th, 8th weeks. The exercise program adherence of the intervention group was followed up through telephone/face-to-face interviews in weeks 1-8. Data were collected using the Numerical Pain Rating Scale, Fall Follow-Up Form, the CIPNAT scale, EORTC QLQ-C30 and EORTC QLQ-CR29 scales. Mann-Whitney U Test, Chi-square test, Wilcoxon signed test, and Friedman test were used to analyze the data.
RESULTS: The study found that as of week 4th, the intervention group experienced less pain severity than the control group (p < 0.001); at week 8th, the peripheral neuropathy symptoms of the intervention group decreased compared to the control group (p < 0.05); at weeks 2nd,4th,6th,8th, there was no statistically significant difference in falls (p > 0.05); at week 8th, while there was no significant difference between the groups regarding colorectal cancer quality of life (p > 0.05), the overall cancer quality of life improved in the intervention group (p < 0.05).
CONCLUSIONS: The hand-foot exercises program is effective in chemotherapy-induced peripheral neuropathy-related symptoms, pain severity, and overall cancer quality of life.
BACKGROUND: www.
RESULTS: gov, NCT05873829.