Search

PurposeStudies on the association between peripheral neuropathy (PN) and patient-reported outcomes have mostly overlooked sleep quality. Therefore, we aimed to assess the association between PN and sleep quality in a population-based sample of colorectal cancer (CRC) patients up two years after diagnosis. MethodsAll newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N=340) completed questionnaires about PN (EORTC QLQ-CIPN20) and sleep (PSQI) before initial treatment (baseline) and one and two years after diagnosis. ResultsPatients who developed sensory PN (n=76) or motor PN (n=79) after treatment more often reported poor sleeping scores (PSQI>5) compared with those who did not develop SPN or MPN at 1-year (SPN: 38% vs. 261%, MPN: 37% vs. 14%) and 2-year follow-up (SPN: 38 vs. 23%, MPN: 37% vs. 18%) (all pConclusionsBoth SPN and MPN were significantly associated with the course of sleep quality among CRC patients up to two years after diagnosis. Clinicians should be encouraged to discuss sleep quality with their patients who either report PN or are at risk of developing PN. Implications for survivors: Improving sleep quality among survivors with PN is important, either by reducing PN symptoms, or directly targeting sleep

BACKGROUND: The increasing colorectal cancer (CRC) survivor population highlights the need for dietary recommendations in order to enhance health-related quality of life (HRQoL) and alleviate symptoms of fatigue, chemotherapy-induced peripheral neuropathy (CIPN) and gastro-intestinal problems.OBJECTIVES: Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of post-diagnostic dietary fiber, fruit and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN and gastro-intestinal symptoms in CRC survivors from 6 weeks to 24 months post-treatment.METHODS: In a prospective cohort among stage I-III CRC survivors (n = 459), five repeated study measurements between diagnosis and 24 months post-treatment were executed. Dietary fiber and fruit and vegetable intake were measured by 7-day dietary records. HRQoL, fatigue, CIPN and gastro-intestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed-models to analyze longitudinal associations from 6 weeks until 24 months post-treatment, and used hybrid models to disentangle the overall association into intra-individual changes and inter-individual differences over time.RESULTS: Higher dietary fiber intake, fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intra-individual analyses showed that an increase of 10 g/d in dietary fiber within individuals over time was associated with better physical functioning (β: 2.3; 95% CI: 0.1, 4.4), role functioning (ability to perform daily activities - 5.9; 1.5, 10.3), and less fatigue (-4.1; -7.7,-0.5). An average increase in fruit and vegetable intake of 100 g/d between individuals over time was predominantly associated with less fatigue (-2.2; -4.2,-0.3). No associations were found with CIPN and gastro-intestinal symptoms.CONCLUSION: Our results suggest that increasing dietary fiber, fruit and vegetable intake is related to better physical and role functioning and less fatigue in the first two years after the end of treatment for CRC.Registration: The EnCoRe study was registered at trialregister.nl as NL6904 (former ID: NTR7099).

We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions. No mutations were found in the causative genes for diseases known to be related to intranuclear inclusions; however, a novel variant in MT-TC was found. The association between intranuclear inclusions and this newly identified MERRF-associated variant is unclear; however, the rare complication of intranuclear inclusions in a patient with typical MERRF symptoms should be noted for future studies.

HIV is one of the most important risk factors of tuberculosis (TB)-related morbidity and mortality. Isoniazid preventive therapy (IPT) is recommended to prevent latent TB reactivation in patients with HIV. However, due to multiple therapies and comorbidities, these patients are predisposed to adverse drug reactions (ADRs) that lead to increased morbidity and mortality. The aim of this study was to determine the prevalence and associated factors of suspected IPT-linked ADRs in HIV-positive patients using IPT.A cross-sectional study was conducted between February and March 2020 at 3 regional referral hospitals (RRHs) in central Uganda. We sampled 660 HIV-positive patients aged 10 years or older who received IPT between July and December 2019 inclusive. Patients were interviewed using a pretested structured questionnaire, and their treatment records were reviewed. A modified Poisson regression model with clustered robust standard errors was used to identify factors associated with suspected IPT-linked ADRs.The prevalence of the suspected ADRs was 51% (334 of the 660; 95% confidence interval [CI]: 18% to 83%). Patients self-reported 7-fold the number of suspected ADRs documented in the clinical files by the health care workers. Musculoskeletal symptoms were the most frequently experienced reaction (14%), followed by dizziness (13%) and peripheral neuropathy (11%). Serious suspected ADRs were experienced by 12% of the study participants; the most common were hepatotoxicity (26%), dizziness (23%), and neuropathy (17%). Female sex (aPR [adjusted prevalence ratio]: 0.92, 95% CI: = 0.88 to 0.95), study site (aPR: 1.09, 95% CI: = 1.09 to 1.18), level of education (aPR: 0.94, 95% CI: = 0.94 to 0.99), history of TB (aPR: 0.93, 95% CI: = 0.87 to 0.99), good IPT adherence (aPR: 1.16, 95% CI: = 1.05 to 1.29), and use of protease inhibitor (PI)-based antiretroviral therapy (aPR: 1.01, 95% CI: = 1.00 to 1.02) were significantly associated with suspected IPT-linked ADRs.The prevalence of suspected IPT-linked ADRs is high, and hepatotoxicity is the most commonly reported serious suspected ADR. Patients self-reported more suspected ADRs than those documented in clinical files by health care workers. Patient engagement could improve ADR detection and potentially strengthen the pharmacovigilance system. Patients with a high risk of ADR ought to be monitored regularly to enable early detection and management.

Background: It is unclear whether glycemic variability (GV) is a risk factor for diabetic peripheral neuropathy (DPN), and whether control of GV is beneficial for DPN. The purpose of this study was to investigate the effect of GV on peripheral nerve damage by inducing glucose fluctuation in streptozotocin-induced diabetic rats.Methods: Rats were divided into four groups: normal (normal glucose group [NOR]), diabetes without treatment (sustained severe hyperglycemia group; diabetes mellitus [DM]), diabetes+once daily insulin glargine (stable hyperglycemia group; DM+LAN), and diabetes+once daily insulin glargine with twice daily insulin glulisine (unstable glucose fluctuation group; DM+Lantus [LAN]+Apidra [API]). We measured anti-oxidant enzyme levels and behavioral responses against tactile, thermal, and pressure stimuli in the plasma of rats. We also performed a quantitative comparison of cutaneous and sciatic nerves according to glucose fluctuation.Results: At week 24, intraepidermal nerve fiber density was less reduced in the insulin-administered groups compared to the DM group (P0.05; 16.2±1.6, 12.4±2.0, 14.3±0.9, and 13.9±0.6 for NOR, DM, DM+LAN, and DM+LAN+API, respectively). The DM group exhibited significantly decreased glutathione levels compared to the insulin-administered groups (2.64±0.10 μmol/mL, DM+LAN; 1.93±0.0 μmol/mL, DM+LAN+API vs. 1.25±0.04 μmol/mL, DM; P

Relevance. Peripheral neuropathy (PNP) in urogenital chlamydia reactive arthritis (CRA) is described as single observations, and many clinical and pathogenetic aspects of this lesion of the nervous system remain unclear. Objective of the study: to evaluate the incidence and nature of the clinical course of PNP in CRA, the connection of the nerve and joint injuries, to explore the questions of pathogenetic constructions of this neuropathy, to identify risk factors. Material and methods. We observed 101 patients with CRA, mean age of them was 32 years, disease duration — 4 years, and the male to female ratio — 1 : 1. In 90 % of CRA cases, Chlamydia trochamatis was found in prostatic secretions, in scraps from the urethra, the cervix, the vaginal wall, in 83 % — positive serologic tests for chlamydia infection. Results. Signs of PNP in CRA were in 19 % of patients in the ratio of mononeuropathy to polyneuropathy as 1 : 1, with motor, sensory and mixed disorders in a ratio of 1 : 3 : 6, the presence of autonomic changes in every second patient and more frequent distal localization of the process in the hands, which is influenced by the severity of the articular syndrome, high levels of antichlamydia antibodies in the blood, and the axonal and demyelinating indicators of electroneuromyography — by the severity of urogenital lesions and the presence of Guillain-Barre syndrome. A high rate of arthritis progression is a prognosis-negative sign of PNP course in patients with CRA. The pathogenic constructions of PNP involve the inflammatory immune proteins, disturbances of vascular endothelial function and physicochemical surface rheological pro­perties of the serum. Conclusion. PNP takes place in every fifth patient with CRA, correlates with clinical and laboratory signs of joint disease, and in the future will be useful to identify actively this pathology of the nervous system for the subsequent timely rehabilitation, and CRA seropositivity for cyclic citrullinated peptide antibodies is a risk factor for such PNP.

Ahmed Esmat,1 Mahmoud I Elshamy,2 Doaa Mohamed Zakaria,3 Zakarya Shady,4 Eman Roshdy Mohamed,3 Nashwa El-Khouly,3 Marwa M Hassan,3 Fatma M El-Senosy3 1Department of Neurology, Al-Azhar University, Faculty of Medicine, Cairo, Egypt; 2Department of Radiology, Al-Azhar University, Faculty of Medicine, Cairo, Egypt; 3Department of Internal Medicine, Faculty of Medicine (Girls), Al-Azhar University, Cairo, Egypt; 4Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, EgyptCorrespondence: Zakarya Shady Tel +201001281304Email zakaryashady96@yahoo.comPurpose: Diabetes is a documented risk factor for peripheral neuropathy. It was reported that associated hypertension could increase this risk. The present study aimed to assess the effect of hypertension and diabetes on median nerve using high-resolution ultrasound.Methods: The study includes 50 hypertensive patients (HTN group), 50 diabetic patients (DM group), 50 patients with coexisting diabetes and hypertension (HTN + DM group) and 50 healthy controls. Median nerve affection in the studied groups was studied by vibration perception thresholds (VPT). The median nerve cross-sectional area was determined at the nerve cross-sectional area of the median nerve at the carpal tunnel by high-resolution ultrasound. Clinical symptoms were assessed using Toronto Clinical Severity Score (TCSS).Results: There was significantly higher median nerve CSA in all patient groups in comparison to controls. HTN + DM group had significantly higher median nerve CSA when compared with DM group. Patients with peripheral neuropathy in HTN + DM and DM groups had significantly higher median nerve CSA than patients without. Using ROC curve analysis, it was shown that median CSA could successfully distinguish patients with peripheral neuropathy from patients without in HTN + DM group [AUC (95% CI): 0.71 (0.54– 0.89)] and in DM group [AUC (95% CI): 0.86 (0.72– 0.99)].Conclusion: Hypertensive patients with and without diabetes have significantly higher median nerve CSA when compared with controls.Keywords: hypertension, peripheral neuropathy, high-resolution ultrasound, diabetes mellitus, median nerve

Introduction Elimination or blocking of astrocytes could ameliorate neuropathic pain in animal models. MiR-125a-5p, expressed in astrocyte derived extracellular vesicles, could mediate astrocyte function to regulate neuron communication. However, the role of miR-125a-5p in DPN (diabetic peripheral neuropathy) remains elusive. Materials and methods Type 2 diabetic mouse (db/db) was used as DPN model, which was confirmed by detection of body weight, blood glucose, mechanical allodynia, thermal hyperalgesia, glial fibrillary acidic protein (GFAP) and monocyte chemoattractant protein-1 (MCP-1). Astrocyte was isolated from db/db mouse and then subjected to high glucose treatment. The expression of miR-125a-5p in db/db mice and high glucose-induced astrocytes was examined by qRT-PCR analysis. Downstream target of miR-125a-5p was clarified by luciferase reporter assay. Tail vein injection of miR-125a-5p mimic into db/db mice was then performed to investigate role of miR-125a-5p on DPN. Results Type 2 diabetic mice showed higher body weight and blood glucose than normal db/m mice. Thermal hyperalgesia and mechanical allodynia were decreased in db/db mouse compared with db/m mouse, while GFAP and MCP-1 were increased in db/db mouse. High glucose treatment enhanced the protein expression of GFAP and MCP-1 in astrocytes. Sciatic nerve tissues in db/db mice and high glucose-induced astrocytes exhibited a decrease in miR-125a-5p. Systemic administration of miR-125a-5p mimic increased mechanical allodynia and thermal hyperalgesia, whereas it decreased GFAP and MCP-1. TRAF6 (tumor necrosis factor receptor associated factor 6) was validated as target of miR-125a-5p. Conclusion MiR-125a-5p in astrocytes attenuated DPN in db/db mice by up-regulation of TRAF6, which indicated the potential therapeutic effect.

Although diabetic peripheral neuropathy is the most common diabetic microangiopathic complication, several other neuropathy syndromes can occur in the context of diabetes. We describe a rare case of polyneuropathy associated with diabetic ketoacidosis in a patient with new-onset type 1 diabetes. A 42-year-old man with diabetic ketoacidosis was admitted to our hospital with complications of respiratory and renal failure requiring mechanical ventilation and hemodialysis, respectively. After diabetic ketoacidosis improved from the critical state, he developed upper- and lower-limb paralysis with sensory disturbances and pain, as well as right facial paralysis, left recurrent nerve paralysis, and left hypoglossal nerve paralysis. Autonomic nervous function was also impaired. As the pathophysiology, prevention, and treatment of polyneuropathy associated with diabetic ketoacidosis are unclear, the neurologic function of diabetic ketoacidosis patients should be closely monitored.

Background. Paclitaxel-induced peripheral neuropathy (PIPN) is a major side effect of paclitaxel in patients with cancer with no fully known mechanisms. The aim of the study was to investigate the fine sub-microscopic structure of the spinal cord anterior horn neurons in PIPN combined with 2-ethyl-6-methyl-3-hydroxypyridine succinate administration. Methods. The experiment was performed on 80 white rats, which were administered intraperitoneally with Paclitaxel (Actavis, Romania), pre-dissolved in an isotonic saline at a dose of 2 mg / kg body weight four times a day to achieve a dose of 8 mg / kg. Then 48 of these animals were injected intraperitoneally 2-ethyl-6-methyl-3-hydroxypyridine succinate at a dose of 10 mg / kg (32 rats received intraperitoneally water for injection). Observation periods were 1, 7, 14, 21, 28 days. Results. We found that 2-ethyl-6-methyl-3-hydroxypyridine corrects the morpho-functional state of the motor neurons of the spinal cord and revealed a positive metabolic effect on them. Conclusion. This was manifested by the improvement of the electron microscopic picture of the neuronal structures responsible for their protein-synthetic (granular endoplasmic reticulum, ribosomes and polysomes), respiratory (mitochondria), and protective (lysosomes) functions.

Pruritus associated with chronic kidney disease is a frequent and disabling symptom in patients with severe chronic kidney disease treated by dialysis. It is associated with a poor quality of life, an increased risk of comorbidities and even mortality. Nevertheless, its prevalence is underestimated by nephrologists. The pathophysiology of pruritus associated with chronic kidney disease is not well understood, but several mechanisms seem to contribute to its occurrence: accumulation and skin deposition of uremic toxins, peripheral neuropathy causing an activation of the pruritogenic cowhage pathway, chronic microinflammation, opioid imbalance, and kidney disease-related skin xerosis. Optimization of the treatment of chronic kidney disease treatment, of dialysis parameters, and general skin care measures should always be performed prior to the introduction of systemic therapy targeting one or more of these mechanisms. The available therapeutic trials remain mostly at high risk of bias, with small patient numbers. Gabapentinoids are the molecules recommended as first-line therapy. Peripheral opioid agonists could find a place of choice in the treatment of pruritus associated with chronic kidney disease and will soon be available in France. The low level of evidence for the other molecules does not currently allow us to specify a second-line treatment for this condition.

One of the most prevalent causes of vasculitis is bacterial infection. An infection that causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is uncommon and not reported frequently. We report a case of a 74-year-old male who presented with fever for ten days and was found to have brucellosis. Then, he was diagnosed with Guillain-Barré syndrome (GBS) and started on immunoglobulin (IVIG) for one week without a response. His fever was still persistent despite appropriate antibiotic therapy. Rheumatology evaluation revealed a history of multiple joint pain and swelling, elevated inflammatory marker, and a high titer of P-ANCA. Steroid therapy was started initially on the background of antibiotics therapy. His fever and other symptoms showed marked improvement after one week. However, P-ANCA titer was still elevated. The decision was made to treat the patient as a case of brucellosis-induced P-ANCA vasculitis. Azathioprine was added, and steroid was maintained for one month and then it was tapered gradually. All symptoms improved from the third month of follow-up except weakness from peripheral neuropathy with normalization of P-ANCA titer. His condition remained stable after six months of follow-up. Clinicians should be aware of the possibility of infection-induced vasculitis, particularly when patients’ symptoms persist despite the appropriate use of antibiotics.

Background Diabetic neuropathy(DN) is the least recognized complication of diabetes mellitus and may start early in the course of disease. Aldose reductase(AKR1B1) gene promoter Z-2/Z-2 polymorphism increases the expression of AKR1B1enzyme and may contribute to DN. Subjects We evaluated 108 type 1 diabetes(T1D) children and adolescents (mean±SD age:13.5±3.46 years, disease duration:5.3±3.4 years) and 150 healthy controls (age:11.9±2.7 years). Methods In both groups, pupillary dilation(PD) in darkness, postural blood pressure test(PBPT) and vibration sensation thresholds(VST) in upper and lower limbs were estimated as indices of autonomic and peripheral neuropathy, respectively. Nerve conduction studies(NCS) were performed in patients as peripheral neuropathy index. The polymorphisms of AKR1B1gene were evaluated using microsatellite(AC)n sequence Z. Results PBPT, PD and VST impairments were more frequent in patient group compared with controls, while 38.6% of patients exhibited NCS abnormality. Gender, age, pubertal status, height, BMI, diabetes duration, HbA1c and anti-GAD titers were associated with neuropathy indices in patients. There was a strong correlation between PD and NCS in patients, while homozygous patients for Z-2 AKR1B1 gene polymorphism had higher prevalence of abnormal NCS (83.3% vs 34.6%), PD (62.5% vs 31,5%) and PBPT values compared with heterozygous or negative patients. Homozygous AKR1B1 status predicted PD, NCS and PBPT variance, while PD, VST, NCS and PBPT parameters accurately discriminated homozygous AKR1B1 patients. Conclusions Impaired indices of peripheral and autonomic DN were present in a significant proportion of young T1D patients. PD, VST, NCS and PBPT parameters were simultaneously associated with homozygous state of AKR1B1 Z-2 gene polymorphism, implicating polyol metabolism with both autonomic and peripheral neuropathies. This article is protected by copyright. All rights reserved.

Oncologists considered platinum-based medicines as potent cytotoxic agents. Despite their efficacy in combination chemotherapy regimens for many solid tumors, they have many substantial side effects that limit their use. There is no known prophylactic strategy for platinum drugs-induced neurotoxicity, which limit a therapeutic dose benefit. This review highlights the etiology of platinum-drugs-induced neuropathy, and covers the preventative and therapeutic options for cancer patients. It focuses on clinical studies conducted between 2010 and 2020. Loss of functional indications such as touch, vibration and joint location, as well as diminished or missing deep tendon reflexes in the upper and lower limbs are all markers of neurotoxicity. These side effects may last for months or years after treatment, lower quality of life, and creating a substantial survivorship issue. DNA damage, oxidative stress, mitochondrial dysfunction, dysregulation of intracellular signaling, impairment of voltage gated ion channel function, and neuro-inflammation have all been proposed as mechanisms for chemotherapy-induced peripheral neuropathy (CIPN). There are no proven pharmaceutical or nutritional therapies to prevent CIPN. Several anti-CIPN medications have been investigated, but either had no effect or had an effect in a limited sample study. Supportive care medications such anti-epileptics and antidepressants are used to treat CIPN.

Subclinical hypothyroidism (SCH) is associated with diabetic peripheral neuropathy (DPN); however, the mechanism underlying this association remains unknown. This study is aimed at examining neurofunctional and histopathological alterations in a type 2 diabetes (T2DM) mouse model of SCH and investigating the impact of thyroid-stimulating hormone (TSH) in an in vitro DPN cell model established using RSC96 cells under high glucose (HG) and palmitic acid (PA) stimulation. Our results indicated that T2DM, in combination with SCH, aggravated abnormal glucose and lipid metabolism in T2DM and dramatically destroyed the peripheral nervous system by increasing paw withdrawal latency, decreasing motor nerve conduction velocity, and exacerbating ultrastructural deterioration of the damaged sciatic nerve caused by diabetes. Furthermore, the results of our in vitro experiments showed that TSH intensified HG/PA-induced RSC96 cell damage by inducing oxidative stress, mitochondrial dysfunction, and apoptosis. More importantly, TSHR knockout or inhibition of PA-induced TSHR palmitoylation could alleviate the apoptosis induced by TSH. Overall, in this study, the novel mechanisms by which TSH, as an independent risk factor for DPN progression, aggravating Schwann cell apoptosis and demyelination, are elucidated. These findings indicate that TSHR could be a potential target for both the prevention and treatment of DPN and, possibly, other microvascular diseases, and have implication in the clinical management of patients with DPN.

Background Oxaliplatin is a key drug in treatment of gastrointestinal (GI) cancer. Peripheral neuropathy (PN) is a troublesome and dose-dependent adverse effect of oxaliplatin. It can occur in two distinct forms: acute and chronic. Its incidence is estimated about 65-98%, of which 22% of cases need to stop chemotherapy. In some cases, PN has a long-lasting effect on patient's quality of life (QOL). Therefore, this study was done to evaluate efficacy of duloxetine on prevention of oxaliplatin- induced peripheral neuropathy (OIPN) in patients with GI cancer. Methodology In this randomized and double -blind clinical trial study conducted in a tertiary teaching hospital, eligible patients were divided into two groups. Treatment group received duloxetine the day before initiation of chemotherapy regimen at a dose of 30 mg/day for one week and then, the dose was titrated up to 60 mg/day until 12 weeks. For placebo group, one placebo capsule was prescribed daily for one week followed by 2 capsules daily until 12 weeks. In each of chemotherapy courses, PN was assessed using national cancer institute-common terminology criteria for adverse effects (NCI-CTCAE v4.03). Also, chemotherapy -related QOL at the baseline and 12 weeks was assessed by functional assessment of cancer treatment gynecologic oncology group - neurotoxicity (FACT/GOG-NTX). Results Forty patients were randomly assigned to treatment and placebo groups which were similar to each other in terms of chemotherapy regimen, type, and stage of cancer. Analysis of results obtained from the NCI-CTCAE (v4.03) showed that duloxetine could prevent worsening of paresthesia more than placebo ( P = 0.025) and patients in duloxetine group experienced less peripheral sensory neuropathy ( P = 0.001) than placebo group. Analysis of results obtained from the FACT/GOG-NTX demonstrated a significant worsening of tingling and discomfort in hands ( P = 0.002, 0.001, respectively) and feet ( P = 0.017, 0.019, respectively) in placebo group compared to duloxetine group. Also, patients experienced more cold temperature -induced pain in extremities ( P = 0.001) in placebo group compared to duloxetine group. On the other hand, duloxetine could not improve QOL ( P = 0.06) and had not significant effects on trouble feeling the shape of small objects in hand ( P = 0.420) or trouble buttoning buttons ( P = 0.086). The P-value < 0.05 was considered to be statistically significant.

Spinal cord stimulation (SCS) has been suggested as a treatment option for patients with painful diabetic neuropathy (PDN). We conducted a systematic review and undertook a meta-analysis on individual patient data from randomised controlled trials (RCTs) to assess the effectiveness of SCS for the management of PDN. Electronic databases were searched from inception to May 2020 for RCTs of SCS for PDN. Searches identified 2 eligible RCTs (total of 93 patients with PDN) and 2 long-term follow-up studies of one of the RCTs. Individual patient data were obtained from the authors of one of these RCTs. Meta-analysis showed significant and clinically meaningful reductions in pain intensity for SCS compared with best medical therapy alone, pooled mean difference (MD) -3.13 (95% confidence interval [CI]: -4.19 to -2.08) on a 10-point scale at the 6-month follow-up. More patients receiving SCS achieved at least a 50% reduction in pain intensity compared with best medical therapy, pooled risk ratio 0.08 (95% CI: 0.02-0.38). Increases were observed for health-related quality of life assessed as EQ-5D utility score (pooled MD 0.16, 95% CI: 0.02-0.30) and visual analogue scale (pooled MD 11.21, 95% CI: 2.26-20.16). Our findings demonstrate that SCS is an effective therapeutic adjunct to best medical therapy in reducing pain intensity and improving health-related quality of life in patients with PDN. Large well-reported RCTs with long-term follow-up are required to confirm these results. ABSTRACT: Spinal cord stimulation (SCS) has been suggested as a treatment option for patients with painful diabetic neuropathy (PDN). We conducted a systematic review and undertook a meta-analysis on individual patient data from randomised controlled trials (RCTs) to assess the effectiveness of SCS for the management of PDN. Electronic databases were searched from inception to May 2020 for RCTs of SCS for PDN. Searches identified 2 eligible RCTs (total of 93 patients with PDN) and 2 long-term follow-up studies of one of the RCTs. Individual patient data were obtained from the authors of one of these RCTs. Meta-analysis showed significant and clinically meaningful reductions in pain intensity for SCS compared with best medical therapy alone, pooled mean difference (MD) -3.13 (95% confidence interval [CI]: -4.19 to -2.08) on a 10-point scale at the 6-month follow-up. More patients receiving SCS achieved at least a 50% reduction in pain intensity compared with best medical therapy, pooled risk ratio 0.08 (95% CI: 0.02-0.38). Increases were observed for health-related quality of life assessed as EQ-5D utility score (pooled MD 0.16, 95% CI: 0.02-0.30) and visual analogue scale (pooled MD 11.21, 95% CI: 2.26-20.16). Our findings demonstrate that SCS is an effective therapeutic adjunct to best medical therapy in reducing pain intensity and improving health-related quality of life in patients with PDN. Large well-reported RCTs with long-term follow-up are required to confirm these results.

A variety of studies have demonstrated the role of lipocalin 2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D). A total of 207 participants with T2D and 40 participants with normal glucose tolerance (NGT) were included in this study. All participants were classified into DPN group and non-DPN (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an ELISA technique. Serum LCN2 levels in NGT group were lower than those in either DPN group (P = 0.000) or NDPN group (P = 0.043), while serum LCN2 levels in DPN group were higher than NDPN group (P = 0.001). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, P = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides, and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (odds ratio (OR) = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D. Our report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

Objective The Measure of Ovarian Symptoms and Treatment (MOST-T35) is a patient-reported symptom index, developed and validated in the context of palliative chemotherapy for recurrent ovarian cancer (OC). We aimed to develop and validate a version suitable for surveillance of symptoms following first-line treatment for OC to support clinical follow-up. Methods In a prospective study of women following completion of first-line chemotherapy for OC, patients completed MOST-T35 every 3 months for up to 3.5 years and other patient-reported outcome measures. Construct validity (Spearman's correlations), discriminative validity (t-tests/ANOVAs assessing differences between clinically distinct groups), ability to detect clinically important symptoms (receiver operating characteristic analysis), and responsiveness (t-tests examining change) were assessed. Results Data from 726 women who received ≥3 cycles of chemotherapy, did not progress within 3 months, and completed ≥one MOST-T35 were analysed. The revised version, MOST-S26, has 26 items and 5 multi-item indexes: peripheral neuropathy (MOST-NTx), disease or treatment-related (MOST-DorT), abdominal (MOST-Abdo), and psychological symptoms (MOST-Psych), and MOST-Wellbeing, plus 9 individual items. Construct validity was confirmed (r range = 0.43–0.88). Discriminative validity confirmed expected differences between groups. MOST-NTx and MOST-Psych detected improvements in peripheral neuropathy and psychological symptoms respectively, whereas MOST-Abdo detected worsening of abdominal symptoms pre-recurrence. Conclusions This study developed and validated the MOST-S26, for surveillance of women in follow-up after first-line chemotherapy for OC. MOST-S26 reliably detected improvement in symptoms of peripheral neuropathy, psychological distress and may detect symptoms of relapse. Administration of MOST-S26 in follow-up consultations could identify concerning symptoms and facilitate timely and appropriate intervention.

Mahmoud A Allam,1 Youssef A Nassar,1 Hosameldeen S Shabana,1 Sadek Mostafa,1 Farag Khalil,1 Hendawy Zidan,1 Mohammed Abo-Ghebsha,2 Amir Abdelghaffar,3 Ahmed Essmat,3 Essam Elmahdi4 1Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 2Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 3Department of Neurology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 4Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, EgyptCorrespondence: Mahmoud A AllamDepartment of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, 11884, EgyptTel +20222602687Fax +20224020184Email dr.mahmoudallam75@gmail.comBackground and Aim: Diabetic peripheral neuropathy (DPN) is one of the most common and disabling complications of DM. Many studies documented the prevalence of clinical and subclinical hypothyroidism (SCH) in diabetic patients but not in the particular group of patients with DPN. The present study aimed to determine the prevalence of SCH in DPN patients and to evaluate its association with severity of DPN.Patients and Methods: The present cross-sectional study was conducted on 300 consecutive patients with DPN. The clinical manifestations of DPN were documented according to the validated Arabic version of the Michigan Neuropathy Screening Instrument. Severity of DPN was categorized into mild (6– 8 points), moderate (9– 11 points) or severe (12+ points) according to the Toronto Clinical Scoring System. All patients were submitted to careful history-taking and full clinical and neurological examination. Patients were diagnosed with SCH if they had TSH level above the upper limit of the normal reference range in association with normal free thyroxine (FT4) level.Results: SCH was prevalent in 53 patients (17.7%, 95% CI: 13.5%– 22.5%). Patients with SCH had significantly higher frequency of severe DPN (52.8% versus 28.3%, p=0.003). It was also shown that patients with SCH had significantly higher HbA1c (8.4 ± 1.0 versus 7.3 ± 1.2%, p< 0.001) and HOMA-IR (3.7 ± 0.8 versus 2.7 ± 0.9, p< 0.001) when compared with patients without SCH. Logistic regression analysis identified patients’ age [OR (95% CI): 1.06 (1.03– 1.08), p< 0.001], HbA1c [OR (95% CI): 2.2 (1.7– 2.9), p< 0.001] and SCH [OR (95% CI): 7.7 (3.6– 15.5), p< 0.001] as independent predictors of DPN severity.Conclusion: The present study showed that SCH is highly prevalent in DPN patients and is independently related to its severity.Keywords: diabetes mellitus, diabetic peripheral neuropathy, subclinical hypothyroidism, thyroid hormones, thyroid dysfunction

PURPOSE To evaluate the association between severity of hepatic steatosis/fibrosis with clinical, laboratory, and echocardiographic characteristics, including visceral obesity and type 2 diabetes mellitus (T2DM)-related micro- and macrovascular complications in diabetic patients with non-alcoholic fatty liver disease (NAFLD). METHODS We studied 60 consecutive NAFLD outpatients with T2DM, recording several demographic and clinical characteristics, trunk and visceral fat, cardiac ultrasound, and micro- and macrovascular complications of diabetes mellitus including microalbuminuria, diabetic peripheral neuropathy, peripheral vascular disease, and cardiac autonomic function. Severity of steatosis and fibrosis was evaluated with abdominal ultrasound and liver stiffness measurements, respectively. RESULTS Twenty-three (41%) of the patients had grade 1 steatosis and mean liver stiffness was 7.5 ± 3 kPa. After applying Bonferroni correction for multiple comparisons, ferritin concentration was the only factor significantly different between patients with mild (grade 1) compared to those with moderate/severe (grade 2/3) steatosis and showed good discriminative ability for the presence of moderate/severe steatosis (AUC: 0.74, sensitivity 88%, specificity 48%, PPV 74%, and NPV 72%). In addition, waist circumference was the only factor associated with the presence of significant fibrosis (≥ F2) with very good discriminative ability (AUC: 0.77, sensitivity 89%, specificity 45%, PPV 75%, and NPV 70%). CONCLUSION Specific clinical and laboratory characteristics, which may be determined via widely accessible and noninvasive techniques, were associated with severity of diabetics NAFLD, taking into account echocardiographic characteristics, visceral obesity, and T2DM-related systemic complications.

Bortezomib (Btz) shows robust efficacy in patients with multiple myeloma (MM); however, some patients experience suboptimal responses and show specific toxicities. Therefore, we attempted to identify specific HLA alleles associated with Btz‐related toxicities and response to treatment. Eighty‐two transplant‐ineligible patients with newly diagnosed MM enrolled in a phase II study (JCOG1105) comparing two less intensive melphalan, prednisolone, plus Btz (MPB) regimens were subjected to HLA typing. The frequency of each allele was compared between the groups, categorized based on toxicity grades and responses to MPB therapy. Among 82 patients, the numbers of patients with severe peripheral neuropathy (PN; grade 2 or higher), skin disorders (SD; grade 2 or higher), and pneumonitis were 16 (19.5%), 15 (18.3%), and 6 (7.3%), respectively. Complete response was achieved in 10 (12.2%) patients. Although no significant HLA allele was identified by multiple comparisons, several candidates were identified. HLA‐B*40:06 was more prevalent in patients with severe PN than in those with less severe PN (odds ratio [OR] = 6.76). HLA‐B*40:06 and HLA‐DRB1*12:01 were more prevalent in patients with SD than in those with less severe SD (OR = 7.47 and OR = 5.55, respectively). HLA‐DRB1*08:02 clustered in the group of patients with pneumonitis (OR = 11.34). Complete response was achieved in patients carrying HLA‐DQB1*03:02, HLA‐DQB1*05:01, and HLA‐DRB1*01:01 class II alleles. HLA genotyping could help predict Btz‐induced toxicity and treatment efficacy in patients with MM, although this needs further validation., Four factors, HLA‐B4006, female (sex), Arm A (treatment course), and bone pain, were chosen as explanatory variables using the stepwise method. The carriers of HLA‐B4006 showed the highest odds ratio for the risk of bortezomib‐induced peripheral neuropathy.

Substrate-derived biomarkers are necessary in slowly progressing monogenetic diseases caused by single-enzyme deficiencies to identify affected patients and serve as surrogate markers for therapy response. N-glycanase 1 (NGLY1) deficiency is an ultra-rare autosomal recessive disorder characterized by developmental delay, peripheral neuropathy, elevated liver transaminases, hyperkinetic movement disorder and (hypo)-alacrima. We demonstrate that N-acetylglucosamine-asparagine (GlcNAc-Asn; GNA), is the analyte most closely associated with NGLY1 deficiency, showing consistent separation in levels between patients and controls. GNA accumulation is directly linked to the absence of functional NGLY1, presenting strong potential for its use as a biomarker. In agreement, a quantitative liquid chromatography with tandem mass spectrometry assay, developed to assess GNA from 3 to 3000 ng/ml, showed that it is conserved as a marker for loss of NGLY1 function in NGLY1-deficient cell lines, rodents (urine, cerebrospinal fluid, plasma and tissues) and patients (plasma and urine). Elevated GNA levels differentiate patients from controls, are stable over time and correlate with changes in NGLY1 activity. GNA as a biomarker has the potential to identify and validate patients with NGLY1 deficiency, act as a direct pharmacodynamic marker and serve as a potential surrogate endpoint in clinical trials.

AIMS/INTRODUCTION In this paper, we focused on exploring the diagnostic and predictive clinical utility of ankle-brachial index (ABI) in combination with feet electrochemical skin conductance (FESC) for peripheral artery disease (PAD) in Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS Overall, 183 Chinese T2DM patients were enrolled in this study. The patients were classified into three groups: Group 1 comprised of uncomplicated type 2 diabetics (n = 36), Group 2 consisted of patients with diabetic peripheral neuropathy (n = 103) whereas Group 3 patients displayed peripheral artery disease (n = 44). All patients underwent Sudoscan test using a Sudoscan (Paris, France) and ABI assessment. RESULTS Multivariate logistic regression models revealed that FESC was an independent risk factor of developing PAD in patients with type 2 diabetes. The AUC for diagnostic, positive predictive and negative predictive value of ABI in combination with FESC for PAD were 0.907, 0.733 and 0.920, respectively. The specificity and sensitivity of ABI in combination with FESC for PAD were 0.914 and 0.750, respectively. CONCLUSIONS Ankle-brachial index in combination with FESC can accurately be used in early diagnosis of PAD.

The present study aimed to investigate the role of SIRT3 and inflammatory factors in bortezomib-induced peripheral neuropathy (PN). This prospective observational cohort study included a total of 159 patients of multiple myeloma patients during June 2016 to June 2019. All patients received the strategy of bortezomib and dexamethasone and were further divided into the PN group and the non-PN group. Serum SIRT3, CRP, IL-6 and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA). During the study period, 76 (47.8%) patients developed PN. The inflammatory factors all gradually decreased and SIRT3 levels were gradually increased after treatment by bortezomib combined with dexamethasone compared with the baseline. The levels of all inflammatory factors were markedly higher, while SIRT3 levels were lower in PN patients compared with the non-PN patients at the same time point after treatment. In PN grade III patients, the serum levels of CRP, IL-6 and TNF-α were significantly higher, while serum levels of SIRT3 were markedly lower than the grade I-II patients. SIRT3 was negatively correlated with CRP, IL-6 and TNF-α. After nursing treatment and reduction of bortezomib dose, the levels of SIRT3 significantly increased, while levels of inflammatory decreased in PN patients with grade III. SIRT3 and inflammatory factors showed the potential for diagnosis of bortezomib-induced PN. Besides, SIRT3, IL-6 and TNF-α were the independent risk factors for MM patients developing PN after treatment of bortezomib. Higher inflammatory factors and lower SIRT3 might be associated with the development of bortezomib-induced PN in multiple myeloma patients, which might be reversed by decreased bortezomib dose and proper nursing treatment.

Metformin use over time reduces vitamin B12 levels, according to several studies, and its clinical manifestation can be mistaken as diabetic peripheral neuropathy. In order to investigate vitamin-B12 deficiency in type II diabetic patients with long-term metformin treatment, a link between vitamin B12 and peripheral neuropathy, and to evaluate the quality of life in (T2DM) patients, the current study was done. At Sree Balaji Medical College and Hospital's outpatient and inpatient departments, a prospective observational case-control research was done. The study included 35 healthy volunteers (controls) and 35 Type 2 diabetes patients who had been on metformin for more than six months (cases). Patients' venous blood samples were collected in K2 EDTA vacutainers and centrifuged at 1500 rpm for 10 minutes, settled plasma was transferred into cryo-vials, and parameters such as Vitamin-B12, HbA1c, and CBP were estimated and this is used to conduct the statistical analysis. The prevalence of blood vitamin B12 deficiency and borderline deficiency in T2DM patients is 20.5 percent, while the mean HbA1C values in our study T2DM subjects are 9.07 percent, indicating either poor diabetes control or poor metformin drug compliance. Vitamin B12 insufficiency was found in 83 percent of T2DM patients who had been using metformin for 1 to 10 years. The reliability test was used to assess their quality of life, and the results revealed that the study participants' quality of life was poor.

OBJECTIVES Chronic kidney disease (CKD) is a common cause of restless leg syndrome (RLS). RLS is under-recognized, misdiagnosed and undertreated disorder in our locality. In this study, we aimed to determine the prevalence of RLS due to CKD and its predictors. METHODS This cross-sectional study included 520 patients [male = 200; female = 320; age: 48.45 ± 3.63yrs; uremia duration: 6.44 ± 1.65yrs; CKD5D = 400; CKD3D = 120). RLS diagnosis was done by clinical interviewing according to International RLS Study Group criteria. All underwent detailed biochemical testing and iron and ferritin levels' measurements. Insomnia, depression and anxiety severities were assessed using insomnia sleep index (ISI), Beck Depression Inventory (BDI-II) and State-Trait Anxiety Inventory for Adults (STAI-AD) scales. RESULTS RLS was found in 22.31% [ESKD = 26%, CKD3D = 10%]. Insomnia, depression and anxiety were found in 76.15%, 91.15% and 44.23%, respectively. Insomnia was correlated with depression (r = 0.488, p = 0.001) and anxiety (r = 0.360, p = 0.006) but not RLS. Multiple linear regression analysis showed that ESKD (OR = 3.8, 95%CI = 2.5-8.5, p = 0.001), inadequate dialysis (OR = 4.6, 95%CI = 3.5-8.6, p = 0.001), hyperparathyroidism (OR = 5.1, 95%CI 3.2-13.7, p = 0.0001) and peripheral neuropathy (OR = 5.6, 95%CI = 3.8-12.8, p = 0.0001) were independently associated with RLS. CONCLUSION The prevalence of RLS with CKD is 22.31%. It is 2.6 times more frequent and severe with ESKD compared to CKD3D. It seems that RLS may occur early with CKD and becomes worse with progressive kidney impairment. Also, insomnia, depression and anxiety are common with CKD, however, their severities were not correlated with RLS. Predictors for RLS were ESKD, inadequacy of dialysis, hyperparathyroidism and peripheral neuropathy.

Background Many of the 3.8 million breast cancer survivors in the United States experience long‐term side effects of cancer therapy including peripheral neuropathy (PN). We assessed the prevalence and predictors of PN among women with breast cancer followed in the Women's Health Initiative's Life and Longevity After Cancer survivorship cohort. Methods The study population included 2420 women with local (79%) or regional (21%) stage disease. Presence of PN was based on the reports of “nerve problems and/or tingling sensations” after treatment and PN severity was assessed using the Functional Assessment of Cancer Therapy‐Gynecologic Oncology Group/Neurotoxicity instrument. Logistic regression analysis was used to evaluate the socio‐demographic and clinical factors associated with PN prevalence and severity. Results Initial breast cancer treatment included surgery‐only (21%), surgery and radiation (53%), or surgery and chemotherapy (±radiation) (26%). Overall, 17% of women reported PN occurring within days (30%), months (46%), or years (24%) after treatment and 74% reported ongoing symptoms at a median of 6.5 years since diagnosis. PN was reported by a larger proportion of chemotherapy recipients (33%) compared to those who had surgery alone (12%) or surgery+radiation (11%) (p

Aim To assess the concordance between variations in Neuropad® results and the those in different diagnostic criteria of Diabetic Peripheral Neuropathy, according to various clinical guidelines. Methods A descriptive observational study was conducted of 111 patients with a confirmed diagnosis of diabetes mellitus. The criteria for inclusion in the study were that patients should be aged 18 years or more and have at least 10 years’ history of diabetes mellitus. Results 73 (65.8%) were male and 38 (34.2%) were female. Their mean age was 57.92 ± 13.24 years (95% CI 55.45–60.38). Healthy Neuropad® findings were obtained for 35 right feet (31.5%) and 31 left feet (27.9%). Conclusion Neuropad® is an effective instrument for detecting macro and microvascular complications such as early-stage neuropathy, although its use should always be accompanied by a clinical examination of the foot.

Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive improvements in peripheral arterial disease, foot ulcers, peripheral neuropathy, nephropathy, retinopathy, ischemic heart disease and cerebrovascular disease. In addition, non-alcoholic steatosis and steatohepatitis, which are closely associated with insulin resistance and type 2 diabetes, have been shown to improve with pentoxifylline. Surprisingly, pentoxifylline modestly improves insulin resistance through improvements in capillary blood flow as well as beta cell function and decreased hepatic glucose production. The therapeutic effects of pentoxifylline are complementary to the effects of drugs such as blockers of the renin-angiotensin-aldosterone system when utilized in the therapy of diabetic nephropathy.

Symptoms of peripheral nervous system (PNS) damage are common clinical manifestations of systemic amyloidosis. Peripheral amyloid neuropathy is characterized by a progressive course, leading to the disability of patients; however, the current possibilities of pathogenetic therapy make the early diagnosis of amyloid neuropathy particularly urgent.Objective: to evaluate the informative value of laser confocal microscopy (LCM) of the cornea in diagnosing small fiber neuropathy of peripheral nerves in patients with systemic amyloidosis.Patients and methods. The study included nine patients (three men and six women) with morphologically confirmed primary amyloidosis (ALamyloidosis) and 12 patients (three men and nine women) with hereditary transthyretin amyloidosis (TTR-amyloidosis) verified by genetic and morphological methods. At baseline, the mean age of patients with AL-amyloidosis was 60.6±10.7 years, with hereditary TTR-amyloidosis – 57.1±13.1 years. According to the history of the disease in AL-amyloidosis, the mean duration of clinical symptoms was 2.7±1.4 years, with TTR-amyloidosis – 5.5±3.6 years. 20 age- and sex-adjusted healthy volunteers were included in the control group. All patients underwent a clinical neurological examination with an assessment of the severity of neuropathy according to the Neuropathy Impairment Score (NIS); 21 patients with systemic amyloidosis and all volunteers of the control group underwent LCM of the corneal nerve fibers (CNF). The coefficients of anisotropy (КΔL) and orientation symmetry (Ksym) of the CNF were calculated to assess the severity of damage to the corneal nerves.Results and discussion. Clinical neurological examination in patients with AL-amyloidosis revealed polyneuropathic syndrome (45%), tunnel syndrome (22%), their combination (22%), and autonomic dysfunction in the form of orthostatic hypotension and impaired motility of the gastrointestinal tract (GI tract; 56%). Symptoms in patients with TTR-amyloidosis were characterized by a combination of tunnel neuropathy and sensory-motor polyneuropathy (50%), distal symmetric polyneuropathy (42%). Frequent symptoms of PNS damage in systemic amyloidosis include autonomic neuropathy (56% – in AL-amyloidosis, 92% – in TTR-amyloidosis) presenting with orthostatic hypotension, impaired gastrointestinal motility, hypohidrosis, and dysuria. The mean NIS score, which characterizes the severity of somatic neuropathy, was significantly higher in patients with TTR-amyloidosis than AL-amyloidosis (pConclusion. Clinical polymorphism of peripheral somatic and autonomic nervous systems lesions is typical for patients with systemic amyloidosis. LCM of the cornea is informative in the diagnosis of small fibers neuropathy of peripheral nerves in systemic amyloidosis; however, it cannot establish the nosology of neuropathy.

PurposeChemotherapy-induced peripheral neuropathy (CIPN) is a common adverse events of cancer treatment; however, no drug is recommended for the prevention of CIPN. In Japan, several drugs such as Gosha-Jinki-Gan and duloxetine have been frequently administered for the treatment of CIPN. The aim of this study was to elucidate prescription patterns of drugs administered for the treatment of CIPN caused by oxaliplatin and the association between these drugs and the duration of oxaliplatin treatment.MethodsWe conducted a retrospective nationwide study using the JMDC administrative claims database (January 2005–June 2020). Patients newly treated with oxaliplatin were identified, and prescription patterns of CIPN medication including Gosha-Jinki-Gan, pregabalin, duloxetine, mecobalamin, and mirogabalin were investigated. The primary outcome was the duration of oxaliplatin treatment. Multivariable logistic regression analysis was performed to examine the association between CIPN medication and duration of oxaliplatin treatment.ResultsA total of 4,739 patients who newly received oxaliplatin were identified. Of these, 759 (16.0%) had received CIPN medication. Duloxetine was administered in 99 (2.1%) patients. Multivariable logistic regression analysis revealed that CIPN medication was significantly associated with the prolonged duration of oxaliplatin treatment (odds ratio: 2.35, [95% confidence interval: 1.99-2.77]).Conclusion Real-world data demonstrated that the administration rate of CIPN medication was higher in patients who underwent oxaliplatin treatment for over 6 months. Increasing administration preference of duloxetine and conducting prospective studies to verify the causal relationship between CIPN medication and prolonged duration of oxaliplatin treatment are needed.

Aim of the work To study the frequency of cranial and peripheral neuropathies in systemic lupus erythematosus (SLE), their clinical characteristics, electrophysiological pattern and relation to disease activity. Patients and methods The study included 30 SLE patients and 20 matched healthy controls. Electrophysiological assessment included routine nerve conduction studies for assessment of peripheral nerves and visual evoked potential, blink reflex, and brain stem auditory evoked potential for assessment of the second, fifth, seventh, and eighth cranial nerves, respectively. Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA–SLEDAI) was assessed. Results The mean age of the patients was 35.8 ± 8.6 years, 27 females and 3 males (9:1) with median disease duration 4.5(1.2–8) years and SELENA-SLEDAI of 12.09 ± 4.94. The mean complement-3 (C3) level was 81.2 ± 26.9 mg/dl and C4 was 11.5 ± 4.4 mg/dl. Peripheral neuropathy was detected electrophysiologically in 66.7% and clinically in 53.3% of the patients and was sensory more than motor. Sensory neuropathy was found in 9(30%), sensorimotor in 11(36.7%), demyelinating in 9(30%), axonal in 6(20%) and both axonal and demyelinating in 5(16.7%) patients. 13.3% had subclinical neuropathy. Sensorimotor and sensory neuropathies were detected in 36.7% and 30% of patients, respectively. Cranial neuropathy was not detected in any patient or control clinically or electrophysiologically. Peripheral neuropathy significantly correlated with SELENA-SLEDAI (r = 0.55, p = 0.002) and negatively with C3 and C4 (r = −0.65, p = 0.012 and r = −0.63, p = 0.015 respectively). Conclusion Peripheral neuropathy is a well-recognized but underestimated manifestation of neuropsychiatric SLE with predominance of sensorimotor variant. Peripheral neuropathy is associated with disease activity and complement consumption.

Purpose This review provides an update on the current clinical, epidemiological and pathophysiological evidence alongside the diagnostic, prevention and treatment approach to chemotherapy-induced peripheral neuropathy (CIPN). Findings The incidence of cancer and long-term survival after treatment is increasing. CIPN affects sensory, motor and autonomic nerves and is one of the most common adverse events caused by chemotherapeutic agents, which in severe cases leads to dose reduction or treatment cessation, with increased mortality. The primary classes of chemotherapeutic agents associated with CIPN are platinum-based drugs, taxanes, vinca alkaloids, bortezomib and thalidomide. Platinum agents are the most neurotoxic, with oxaliplatin causing the highest prevalence of CIPN. CIPN can progress from acute to chronic, may deteriorate even after treatment cessation (a phenomenon known as coasting) or only partially attenuate. Different chemotherapeutic agents share both similarities and key differences in pathophysiology and clinical presentation. The diagnosis of CIPN relies heavily on identifying symptoms, with limited objective diagnostic approaches targeting the class of affected nerve fibres. Studies have consistently failed to identify at-risk cohorts, and there are no proven strategies or interventions to prevent or limit the development of CIPN. Furthermore, multiple treatments developed to relieve symptoms and to modify the underlying disease in CIPN have failed. Implications The increasing prevalence of CIPN demands an objective approach to identify at-risk patients in order to prevent or limit progression and effectively alleviate the symptoms associated with CIPN. An evidence base for novel targets and both pharmacological and non-pharmacological treatments is beginning to emerge and has been recognised recently in publications by the American Society of Clinical Oncology and analgesic trial design expert groups such as ACTTION.

Objective: The aim of this study is to determine the frequency of peripheral neuropathy in newly diagnosed cases of type II diabetes mellitus. Study Design: Cross Sectional Study. Setting: Department of Medicine at Avicenna Medical & Dental College, Lahore. Period: 1st February 2020 to 31st July 2020. Material & Methods: One hundred and twenty newly diagnosed patients of type 2 diabetes mellitus were enrolled in this study. Patients detailed demographically recorded after getting written consent. Patients were diagnosed for the duration of 4-weeks and calculated fasting blood sugar (FBS) of ≥126mg/dl, and Random Blood Sugar (RBS) of ≥200 mg/dl or HbA1c ≤6.5. Results: Seventy (58.3%) were males and rest 50 (41.7%) were females with mean age 37.15±10.91 years. Mean body mass index of the patients was 22.48±3.66 kg/m2. Forty two (35%) patients had symptoms of peripheral neuropathy while that patient’s who did not have any symptom was 78 (65%). Same symptoms were observed within 4-weeks and we noticed that 23 (19.2%) patients showed peripheral neuropathy and rest 97 (80.8%) patients did not have any symptoms. Conclusion: The frequency of peripheral neuropathy is higher in early stages of type II diabetes mellitus and its frequency can be reduced to diagnose within a month.

Background and Objective: The diabetic Mellitus common and spiking complication is Diabetic peripheral neuropathy (DPN). It is frequently associated with thyroid dysfunction. The subclinical hypothyroidism prevalence and clinical outcomes have been investigated by various studies. The present study aims to determine the prevalence of subclinical hypothyroidism in diabetic peripheral neuropathy patients. Methods: This cross-sectional study was carried out on 164 diabetic neuropathy patients attending the medicine department of Qazi Hussain Ahmad Medical Complex, Nowshera KPK during the study period from 2020 to 2021. Patients’ demographic details, clinical history, and neurological examination were recorded. Normal free thyroxin value was set as a referential standard for subclinical hypothyroidism diagnosis among all the patients. Diabetic neuropathy patients’ clinical manifestations were recorded as per neurological screening instrument. The clinical scoring system was utilized for DPN severity categorization into mild (6-8), moderate (9-11), and severe (>12). SPSS version 20 and a logistic regression model were used for data analysis. Results: This study enrolled 164 diabetic peripheral neuropathy patients. Of the total 164, 69 (42.1%) were male and 95 (57.9%) were female. The overall mean age was 49.61±13.72 years. The prevalence of subclinical hypothyroidism was 32 [19.5%; 95% CI; 14.3%-23.7%]. The diabetic peripheral neuropathy patients with subclinical hypothyroidism had a higher prevalence of severity 86 [52.4%; 95%CI] compared to DNP patients without SCH 46 [28.04%; 95% CI] with a 3% level of significance. A higher HbA1c and HOMA-IR was found in patients with their respective values were (8.3±1.1 against 7.2±1.3) where p-value

Background: Both Type 1 and Type 2 diabetes can cause neuropathy, which is a frequent and severe consequence. C-peptide depletion may be partly related to in the occurrence of certain diabetic complications. It has been demonstrated that even a little amount of residual C-peptide has a considerable metabolic advantage. Objective: The study’s objective was to predict the relation of plasma C-peptide levels in patients with diabetic neuropathy, and its effect on Na-K ATPase activity. Design and Methods: In this case-control study, 150 individuals have been included: 80 patients with diabetic neuropathy, 40 diabetics without neuropathy and 30 non-diabetic subjects as a control. Patients in the first group were carefully chosen based on their clinical symptoms and nerve conduction studies results. The assessment of plasma C-peptide was done by ELISA, Na-K ATPase enzyme activity by spectrophotometer, and HbA1C by HPLC. Results: Mean plasma C-peptide level and Erythrocyte Na-K ATPase activity were substantially lower in neuropathy type 2 DM patients compared to diabetes without neuropathy and control (p= 0.002, 0.000 respectively). The negative correlation between C-peptide with HbA1c, and diabetes period were all negligible (p= 0.447,0.098), Even though there was a notable negative correlation with age (p= 0.03). On the other hand, the relationship linking C-peptide and Na-K ATPase enzyme activity was shown to be insignificant (p=0.69). Conclusions: Diabetic neuropathy is related to a low C-peptide level. The association between C-peptide and Na-K ATPase enzyme activity, on the other hand, was shown to be insignificant. C-peptide HbA1c, and duration of diabetes all had minor negative associations. How to cite this article:Al-Rikabi EH, Yasser OM, Mousa MJ. Assessment of the Effect of C-Peptide Level on Na-K ATPase Activity In Individuals with Type II Diabetic Peripheral Neuropathy. J Commun Dis. 2021;53(3):213-219. DOI: https://doi.org/10.24321/0019.5138.202159

Diabetic neuropathy is a long-term consequence of diabetes that can cause significant morbidity and a decline in quality of life in many individuals. Low vitamin D levels, in addition to causing rickets in infants and chondrosteoma in adults, may have a role in the development of DM and its underlying disorders, according to a growing body of evidence. Vitamin D deficiency has been linked to type 1 or type 2 diabetes, as well as the microvascular and macrovascular problems that come with it. Vitamin D insufficiency has been linked to diabetic peripheral neuropathy (DPN) as an independent risk factor. Vitamin D, both topical and oral, has been shown to considerably improve DPN symptoms and pain.

Articular syndrome is one of the main signs of the microscopic polyangiitis (MPA), which in some regions of the Earth accounts for over 90 % of all systemic vasculitis (SV), associated with antineutrophil cytoplasmic antibodies (ANCA). It was found that 5 years after the manifestation of MPA, a progressive reduction of the para-articular (epiphyseal) bone mineral density and destruction of the joints begin to form. Many questions related to the nature of the course of joint pathology in specific ANCA-SV require further study. Objective: to evaluate joint damage in patients with MPA and the relationship with extra-articular pathology. Material and methods. We study involved 89 patients with MPA aged 18–78 years old, among which there were 44 % men and 56 % women. The duration of the disease from the first signs of manifestation was 7 years. Acute or subacute course of MPA has been registered in 27 % of cases, and in the rest — chronic one; I degree of the activity of pathological process has been detected in 10 % of cases, II —in 32 %, III — is 58 %. Results. The joint involvement is observed in 60 % of patients with MPA, in 40 % of cases it occurs in the form of oligoarthritis, depends on the presence of pathology in skeletal muscles, pneumopathy or peripheral neuropathy. Clinical, radiological and sonographic signs of articular pathology in MPA are closely associated with patients’ age, disease duration, lesions of the heart, kidneys and skin. In the pathogenetic structures of arthropathy in patients with MPA, C-reactive protein (CRP) and circulating immune complexes (CIC) are involved, and the nature of ANCA (antibodies to myeloperoxidase and proteinase-3) is of small value, while the high blood levels of rheumatoid factor (RF) have certain prognosis-negative significance in terms of the severity of joint pathology. Conclusion. Unfavorable prognostic criteria for the development of joint pathology in patients with MPA are indicators in the blood: CRP > 20 mg/l and CIC > 130 с.u., and the RF values > 60 IU/ml are considered the risk factors for severe arthropathy.

Aims/Introduction Diabetic peripheral neuropathy is a common diabetes‐related microvascular complication. The relationship between peripheral nerve function and glucose variability is unclear. We investigated the association of glucose variability with subclinical diabetic polyneuropathy in a large‐scale sample of patients with type 2 diabetes. Materials and Methods We enrolled 509 individuals with type 2 diabetes who were screened for diabetic peripheral neuropathy and monitored using a continuous glucose monitoring system. Multiple glycemic variability parameters, including the mean amplitude of glycemic excursions, glucose standard deviation (SDgluc) and glucose coefficient of variation were calculated from 3‐day glucose profiles obtained from continuous glucose monitoring. All participants underwent nerve conduction studies, and the composite Z‐scores for nerve conduction parameters were calculated. Results Multivariate logistic regression analyses showed that SDgluc and the conventional risk factor hemoglobin A1c (HbA1c) were independently associated with abnormal nerve function, and the corresponding odds ratios (95% confidence interval) were 1.198 (1.027–1.397, SDgluc) and 1.182 (1.061–1.316, HbA1c), respectively. The composite Z‐score of nerve conduction velocity and response amplitude obviously decreased with greater SDgluc, and the composite Z‐score of distal latency significantly increased with increasing tertiles of SDgluc (all P trend