Polyneuropathy Patients Research Articles

CEPARM: Four decades of dedication to advancing Familial Amyloidotic Polyneuropathy research and patient care

This paper delves into the remarkable journey of theCentro de Paramiloidose Antônio Rodrigues de Mello (CEPARM),located at the Hospital Universitário Clementino Fraga Filho(HUCFF) of UFRJ, over the past four decades, from itsestablishment in 1984 to its emergence as a pioneering institution inthe so called field of Familial Amyloidotic Polyneuropathy (FAP).Founded in response to the urgent need for specialized researchand treatment of this rare genetic disorder prevalent amongindividuals of Portuguese descent mainly with expressivePolyneuropathy (Hereditary Transthyretin Amyloidosis withPolyneuropathy - hATTR-PN) or even Cardyomyopathy (HereditaryTransthyretin Amyloidosis with Cardyomyopathy hATTR-CM),CEPARM has played a crucial role in the evolution of this field.The paper offers a comprehensive overview of thecenter’s development, emphasizing its major achievements,research contributions, and advancements in patient care. Ithighlights CEPARM’s pivotal role in developing innovativetreatment protocols, including the introduction of livertransplantation for FAP and groundbreaking therapies such astafamidis, patisiran, inotersen, vutrisiran, and eplontersen.Additionally, the paper explores CEPARM’s efforts to enhancepatient quality of life through multidisciplinary care and supportprograms.By reflecting on the center’s historical milestones,leadership transitions, and ongoing initiatives, this paperunderscores CEPARM’s unwavering commitment to advancingscientific knowledge and improving patient outcomes mainly in therealm of hATTR-PN.

Intestinal microflora dysbiosis and resistome in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

The aim of the present study is to explore the bacterial diversity within the gut microbiome of chronic inflammatory demyelinating polyneuropathy patient. A stool sample was collected and analyzed to study the gut microbiota through bacterial 16S rRNA gene sequencing. The gut microbiota of chronic inflammatory demyelinating polyneuropathy patient exhibited a dominance of Firmicutes and Bacteroides phyla, with 58.19% and 33.31%, respectively. The data showed a notable abundance of Lachnospiraceae bacterium and Bacteroides sp species, 17.79% and 16.56%, respectively within the gut microbiota chronic inflammatory demyelinating polyneuropathy patient. Lachnospiraceae, a member of the Firmicutes phylum, plays a pivotal role in the production of short-chain fatty acids. At high concentration, short-chain fatty acids can trigger autoimmune leading to the chronic inflammatory demyelinating polyneuropathy. These findings strengthen the possible involvement of short-chain fatty acids in the chronic inflammatory demyelinating polyneuropathy pathogenesis process and could pave new paths in its diagnosis and therapies based on regulation of microbiota dysbiosis.

Dietary phytochemical index and its relationship with diabetic sensorimotor polyneuropathy: a case-control study

Phytochemicals are compounds found in fruits, vegetables, whole grains, nuts and legumes that are non-nutritive but have bioactive properties. A high intake of these compounds is essential for optimal health and disease prevention. No study has investigated the association between Dietary Phytochemical Index (DPI) and polyneuropathy in patients with diabetes. This study aimed to examine the association between DPI and Diabetic Sensory-motor Polyneuropathy (DSPN) in a case-control study. In this case-control study, a total of 185 diabetic patients with DSPN (case group) and 185 sex- and age-matched diabetic patients without neuropathy (control group) were enrolled in this study. Participants were 30–60 years old. A validated food frequency questionnaire was used to measure the dietary intake of all participants. Daily energy derived from phytochemical-rich foods was used to calculate the DPI score. Toronto clinical neuropathy score was applied to define DSPN. Anthropometric data and fasting blood glucose levels were measured using standard methods. The Binary logistic regression was used to estimate Crude and multivariable-adjusted OR (95% CI) for DSPN across tertiles of DPI for the whole population. In the crude model, there was a significant trend across the tertile of DPI (OR highest vs. lowest tertile of DPI = 0.33; 95%CI 0.18, 0.52; P-trend < 0.001). After controlling for age, sex, and energy, a significant reverse association was observed between DPI and DSPN (OR highest vs. lowest tertile of DPI = 0.27; 95%CI 0.15, 0·48; P-trend < 0.001). Moreover, after adjusting for a wide range of confounding variables such as energy intake, physical activity, education, smoking status, and HbA1c, participants in the third tertile of DPI had 75% reduced odds for DSPN (95%CI 0.14, 0.45; P-trend < 0.001). Finally in the full adjusted model, after further adjustment for BMI, observed significant association was remained (OR highest vs. lowest tertile of DPI: 0.24; 95% CI 0.13, 0.14; P-trend < 0.001). Higher intakes of phytochemical-rich foods are associated with lower odds of DSPN.

Effects of Monochromatic Infrared Light on Painful Diabetic Polyneuropathy: Randomized Controlled Trial

Purpose: To evaluate the effect of 890 nm Monochromatic Infrared Light (MIR) associated with a physical therapy protocol on pain in individuals with diabetic Distal Symmetric Polyneuropathy.Methods: Randomized, parallel, double-blind controlled trial conducted with individuals randomly allocated into two groups: an experimental group (EG) with the application of 890 nm MIR associated with physical therapy and a control group that received the same treatment protocol without MIR application. Both groups underwent 18 treatment sessions and were followed up for 10 weeks. Pain assessment took place at four times using the instruments: Leeds Assessment of Neuropathic Symptoms and Signs, Douleur Neuropathique 4, and Brief Pain Inventory. Descriptive, inferential statistics and probabilistic estimates of the magnitude of the intervention's effect on neuropathic pain were used in data analysis (5% significance level).Results: A total of 144 patients were allocated to groups. Lower levels of pain were observed for the EG after 6 weeks of intervention (p < .001) and 30 days after the intervention ended (p < .001). Pain intensity was lower and sleep quality improved (p < .001) for the experiment group, especially in people with severe pain.Conclusions: 890 nm MIR associated with a physical therapy protocol alleviated pain in people with Diabetic Painful Polyneuropathy after 6 weeks of follow-up, showing to be a promising alternative for the control of neuropathic pain due to diabetes mellitus.Clinical Implications: 890 nm MIR improves Painful Diabetic Polyneuropathy patient care due to relief of neuropathic pain.

Polyneuropathy in Patients with Spinocerebellar Ataxias Types 2, 3, and 10: A Systematic Review.

Spinocerebellar ataxia (SCA) is an autosomal dominant hereditary disease with a low prevalence, for which more than 50 types have been described. This group of neurodegenerative diseases can present as different phenotypes with varying progression rates and clinical manifestations of different severities. Herein, we systematically reviewed existing medical literature to describe the main characteristics of polyneuropathy in patients with SCA types 2, 3, and 10. Using relevant keywords, 16,972 articles were identified from the databases. Of these, 5,329 duplicate studies were excluded before screening. Subsequently, 11,643 studies underwent title and abstract review, of which only 49 were selected for full-text review. Among these, 24 studies were included. The medical literature suggests peripheral neuropathy - probably in a polyneuropathy phenotype - in SCA types 2 and 3. It is not possible to determine whether there is peripheral neuropathy in patients with SCA type 10, as there is only one case series in Mexico that described peripheral neuropathy in this group. Further studies are required to investigate peripheral neuropathy in patients with SCA types 2, 3, and 10. The study and description of a possible statistical association between CAG repeats and SARA scale scores with the presence of peripheral neuropathy are important points requiring assessment in future research.

Clinical Value of Stromal Cell Factor (Sdf-1) Determination in Chemotherapy-Induced Peripheral Polyneuropathy in Patients with Hematological Malignancies (Results of a Prospective Cohort Study)

Clinical Value of Stromal Cell Factor (Sdf-1) Determination in Chemotherapy-Induced Peripheral Polyneuropathy in Patients with Hematological Malignancies (Results of a Prospective Cohort Study)

Clinical and molecular insights into A97S variants in hereditary transthyretin amyloid polyneuropathy in South China

Objective This study aims to delineate the clinical profiles of the hereditary transthyretin amyloid polyneuropathy (ATTRv-PN) patients with A97S variant from southern China and the molecular characteristics of this mutant protein. Methods Fifteen ATTRv-PN patients with heterozygous A97S and one patient with homozygous A97S were included in the study. Serum TTR tetramer concentration was quantified through ultra-performance liquid chromatography. Stabilities of A97S-TTR were assessed through in vitro urea-mediated tryptophan fluorescence experiments, and nephelometry was employed in drug response assessment. Results All patients were late-onset (≥50 years) with a mean age of onset at 59.26 ± 5.06 years old. Patients displayed a mixed phenotype featuring sensory-motor neuropathy with autonomic dysfunction and cardiac involvement, such as palpitations and chest pain. Electrophysiological studies showed generally axonal impairment of sensory and motor nerves. Tafamidis-treated patients showed significantly higher TTR tetramer concentrations, approaching healthy controls’ levels. In vitro assessment showed that A97S-TTR was more kinetically stable than the V122I-TTR, and tetramer stabilisers inhibited A97S-TTR amyloid formation by more than 70%. Conclusion This study provides valuable insights into the clinical and molecular characteristics of ATTRv-PN patients with A97S from South China, particularly regarding the differences in disease progression and stability features.

Structure, functions and metabolic features of the peripheral nervous system

Among diseases of the peripheral nervous system, polyneuropathies rank second in frequency of occurrence after vertebrogenic lesions, and among all polyneuropathies, diabetic and alcoholic polyneuropathies account for more than 50 % in prevalence. Knowledge of the structure, function, and metabolic features of the peripheral nervous system is relevant and will allow using pathogenetic approaches in the management of polyneuropathy patients, improving their standard of living and quality of life.

Risk of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. A prospective cohort study.

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. 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. 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. 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.

Predicting chemotherapy toxicity in multiple myeloma: the prognostic value of pre-treatment serum cytokine levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor.

Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events. We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia. Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414). Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.

Anti-neurofascin-155 antibody mediated a distinct phenotype of chronic inflammatory demyelinating polyradiculoneuropathy.

To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.

Cold-evoked potentials in Fabry disease and polyneuropathy.

Fabry disease (FD) causes cold-evoked pain and impaired cold perception through small fiber damage, which also occurs in polyneuropathies (PNP) of other origins. The integrity of thinly myelinated fibers and the spinothalamic tract is assessable by cold-evoked potentials (CEPs). In this study, we aimed to assess the clinical value of CEP by investigating its associations with pain, autonomic measures, sensory loss, and neuropathic signs. CEPs were examined at the hand and foot dorsum of patients with FD (n = 16) and PNP (n = 21) and healthy controls (n = 23). Sensory phenotyping was performed using quantitative sensory testing (QST). The painDETECT questionnaire (PDQ), FabryScan, and measures for the autonomic nervous system were applied. Group comparisons and correlation analyses were performed. CEPs of 87.5% of the FD and 85.7% of the PNP patients were eligible for statistical analysis. In all patients combined, CEP data correlated significantly with cold detection loss, PDQ items, pain, and autonomic measures. Abnormal CEP latency in FD patients was associated with an abnormal heart frequency variability item (r = -0.684; adjusted p = 0.04). In PNP patients, CEP latency correlated significantly with PDQ items, and CEP amplitude correlated with autonomic measures (r = 0.688, adjusted p = 0.008; r = 0.619, adjusted p = 0.024). Furthermore, mechanical pain thresholds differed significantly between FD (gain range) and PNP patients (loss range) (p = 0.01). Abnormal CEPs were associated with current pain, neuropathic signs and symptoms, and an abnormal function of the autonomic nervous system. The latter has not been mirrored by QST parameters. Therefore, CEPs appear to deliver a wider spectrum of information on the sensory nervous system than QST alone.

Vitamin b12 deficit mimics diabetic polyneuropathy in patients taking metformin

Vitamin b12 deficit mimics diabetic polyneuropathy in patients taking metformin

The usefulness of ultrasonography for the early diagnosis of polyneuropathy in patients with type II diabetes mellitus

Background: Diabetic neuropathies, affecting over 50% of diabetes patients, present varied forms of polyneuropathy impacting somatic and autonomic nerves. Clinical assessments, laboratory findings, and nerve conduction studies (NCSs) aid in precise diagnosis, while recent technological advances highlight ultrasonography (US) as a promising, cost-effective diagnostic tool. Aims and Objectives: This study aims to assess the efficacy of US in early polyneuropathy diagnosis in type II diabetes, exploring its potential as an alternative to NCS. Materials and Methods: In this prospective observational study, we enrolled 30 adult patients with type II non-controlled diabetes and 30 age-matched controls, comprising 15 controlled diabetic patients and 15 normal individuals. The comprehensive assessments encompassed history-taking for diabetes duration, hypertension, and diabetic complications, along with clinical examinations and investigations involving nerve electrophysiology and US on one upper limb based on patient complaints. Results: Significant increases in the cross-sectional area (CSA) of the median nerve were observed in diabetic peripheral neuropathy groups compared to controls, with a P&lt;0.001. Similarly, at the level behind the medial epicondyle, the ulnar nerve CSA exhibited a significant increase in the diabetic peripheral neuropathy group (11.7 mm2) compared to controls (6.7 mm2) with a P&lt;0.002. In addition, a significant difference in cross-sectional values was found in the median nerve proximal to the carpal tunnel between the two groups (P&lt;0.05). In contrast, no significant differences were observed at other sites. Regarding the relationship between sonography and NCSs, NCSs showed higher sensitivity, but sonography demonstrated comparable specificity in evaluating diabetic peripheral neuropathy. Conclusion: Peripheral nerve US in the upper limb can be a valuable diagnostic tool for identifying and diagnosing diabetic peripheral neuropathy.

Chronic Inflammatory Demyelinating Polyneuropathy Induced by Immune Checkpoint Inhibitors: Case Reports

Neurological immune-related adverse events (irAE) are rare but potentially fatal complications associated with the use of immune checkpoint inhibitors (ICI). Recently, there has been a trend towards an increase in the incidence of these cases.&#x0D; We present two case reports of demyelinating polyneuropathy in patients with skin melanoma treated with pembrolizumab or nivolumab. Unawareness of neurological irAE induced by ICI leads to delayed diagnosis and medical treatment, and this may result in persistent neurological deficit or even patients’ death. Neurological irAEs include myasthenia gravis, aseptic meningitis, encephalitis, myelitis, inflammatory demyelinating neuropathy, myositis or their combinations, etc. Considering their variability in patients treated with ICI and poor representation in publications, each case report can be of practical value.

Progressive demyelinating polyneuropathy after hematopoietic cell transplantation in metachromatic leukodystrophy: a case series

Metachromatic leukodystrophy (MLD) is a neuro-metabolic disorder due to arylsulfatase A deficiency, causing demyelination of the central and peripheral nervous system. Hematopoietic cell transplantation (HCT) can provide a symptomatic and survival benefit for pre-symptomatic and early symptomatic patients by stabilizing CNS disease. This case series, however, illustrates the occurrence of severely progressive polyneuropathy shortly after HCT in two patients with late-infantile, one with late-juvenile, and one with adult MLD, leading to the inability to walk or sit without support. The patients had demyelinating polyneuropathy before HCT, performed at the ages of 2 years in the first two patients and at 14 and 23 years in the other two patients. The myeloablative conditioning regimen consisted of busulfan, fludarabine and, in one case, rituximab, with anti-thymocyte globulin, cyclosporine, steroids, and/or mycophenolate mofetil for GvHD prophylaxis. Polyneuropathy after HCT progressed parallel with tapering immunosuppression and paralleled bouts of infection and graft-versus-host disease (GvHD). Differential diagnoses included MLD progression, neurological GvHD or another (auto)inflammatory cause. Laboratory, electroneurography and pathology investigations were inconclusive. In two patients, treatment with immunomodulatory drugs led to temporary improvement, but not sustained stabilization of polyneuropathy. One patient showed recovery to pre-HCT functioning, except for a Holmes-like tremor, for which a peripheral origin cannot be excluded. One patient showed marginal response to immunosuppressive treatment and died ten months after HCT due to respiratory failure. The extensive diagnostic and therapeutic attempts highlight the challenge of characterizing and treating progressive polyneuropathy in patients with MLD shortly after HCT. We advise to consider repeat electro-neurography and possibly peripheral nerve biopsy in such patients. Nerve conduction blocks, evidence of the presence of T lymphocytes and macrophages in the neuronal and surrounding nerve tissue, and beneficial effects of immunomodulatory drugs may indicate a partially (auto)immune-mediated pathology. Polyneuropathy may cause major residual disease burden after HCT. MLD patients with progressive polyneuropathy could potentially benefit from a more intensified immunomodulatory drug regime following HCT, especially at times of immune activation.

Utility of single fibre electromyography (SFEMG)and motor unit number estimation technique (MUNE) in the diagnosis and differentiation of polyneuropathies of different aetiology.

To determine whether single fibre electromyography and motor unit number index can distinguish between axonal and myelin lesions in polyneuropathies. This case-control study was conducted at the Department of Medical Physiology, School of Medicine, University of Duhok, Iraq, and the Neurophysiology Department, Hawler Teaching Hospital, Erbil, Iraq, from January 2021 to March 2022. Group A had patients diagnosed with polyneuropathy regardless of the aetiology, while group B had age-matched healthy controls. Both groups were subjected to single fibre electromyography and motor unit number index as well as conventional nerve conduction study and concentric needle electromyography. Data was analysed using SPSS 26. Of the 140 subjects, 60(43%) were patients in group A; 40(67%) males and 20(33%) females with mean age 55.3±7.2 years. There were 80(57%) controls in group B; 43(54%) females and 37(46%) males with mean age 53.81±7.15. Group A had significantly higher single fibre electromyography jitter, and mean consecutive difference (MCD) values than group B (p<0.05). Group A patients with axonal polyneuropathy had a higher mean jitter (MCD) value (36.476.7ms) than those with demyelinating polyneuropathy (23.262.31 ms) (P <0.05). Patients in group A had a motor unit number index value with a significantly lower mean value (p<0.05) when compared to the controls. Axonal polyneuropathy patients had a lower MUNIX value (99.612.8) than demyelinating polyneuropathy patients (149.845.7) (P< 0.05). Single fibre electromyography and motor unit number index could help differentiate between the pathophysiology of axonal and demyelinating polyneuropathy.

Polyneuropathy in systemic sclerosis: exploring the causes and biomarkers.

Systemic sclerosis (SSc) is a rare autoimmune disease with multiple organ involvement; however, the contribution of the nervous system (NS) remains relatively understudied. There are no specific data on the role of the autoimmune response and inflammation in the development of peripheral nerve system (PNS) damage in SSc and markers to assess this damage have yet to be identified. The primary objective of this study was to define the autoimmune mechanisms that lead to neuropathy by identifying antibodies (Abs) that target certain component of the NS or are associated with SSc. The secondary objective was to identify markers of NS damage that correlate with the detection and progression of polyneuropathy (PNP). This study included patients diagnosed with SSc who met ACR/EULAR 2013 classification criteria at two leading Latvian hospitals between January 2016 and December 2021. Patients underwent a nerve conduction study (NCS). The SSc-associated Abs, Abs against myelin-associated glycoprotein (MAG) and anti-ganglioside Abs (GM1, GM2, GD1a, GD1b and GQ1b) were analysed. Potential serum PNS biomarkers-neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF15)-were measured. We recruited 103 Caucasian patients diagnosed with SSc. SSc-associated Abs did not differ significantly between patients with and without PNP (p > 0.05). Anti-MAG and anti-ganglioside Abs in patients with PNP did not present a significant increase above the reference range. NfL, GFAP and GDF15 were significantly elevated in the presence of PNP (p < 0.05), with a moderate to high effect size (r = 0.36-0.65). Our regression analysis revealed a strong association between the HAQ-DI score, older age, male gender and the risk of developing PNP. The development of PNP in patients with SSc is most likely due to ageing, natural progression and the sequelae of the disease. Several serum biomarkers-NfL, GFAP and GDF15-could be used as relevant diagnostic biomarkers for PNP in patients with SSc. Future studies are warranted to validate the diagnostic efficacy of these biomarkers and to unravel the complex interplay of factors leading to PNP in patients with SSc.

Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension.

Small interfering RNA (siRNA) represents a novel, fascinating therapeutic strategy that allows for selective reduction in the production of a specific protein through RNA interference. In the cardiovascular (CV) field, several siRNAs have been developed in the last decade. Inclisiran has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) circulating levels with a reassuring safety profile, also in older patients, by hampering proprotein convertase subtilisin/kexin type 9 (PCSK9) production. Olpasiran, directed against apolipoprotein(a) mRNA, prevents the assembly of lipoprotein(a) [Lp(a)] particles, a lipoprotein linked to an increased risk of ischemic CV disease and heart valve damage. Patisiran, binding transthyretin (TTR) mRNA, has demonstrated an ability to improve heart failure and polyneuropathy in patients with TTR amyloidosis, even in older patients with wild-type form. Zilebesiran, designed to reduce angiotensinogen secretion, significantly decreases systolic and diastolic blood pressure (BP). Thanks to their effectiveness, safety, and tolerability profile, and with a very low number of administrations in a year, thus overcoming adherence issues, these novel drugs are the leaders of a new era in molecular therapies for CV diseases.

Assessment of MiR-191-5p as a Predictive Marker of Early Diabetic Sensorimotor Polyneuropathy in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Assessment of MiR-191-5p as a Predictive Marker of Early Diabetic Sensorimotor Polyneuropathy in Patients with Newly Diagnosed Type 2 Diabetes Mellitus