Translating a Clinical Practice Guideline to a Portuguese, Spanish and English Practice Brief to promote exercise therapy for paediatric Charcot-Marie-Tooth disease.

BACKGROUND: Implementing scientific knowledge in clinical practice is a challenge. In this context, the effective dissemination of scientific findings is of utmost importance. OBJECTIVE: The aim of this study was to develop a Practice Brief in Portuguese, Spanish and English based on a previously published Clinical Practice Guideline to promote safe and effective exercise for children and young people with Charcot-Marie-Tooth disease and related neuropathies (CMT). METHODS: The Practice Brief was developed by eight health professionals from Brazil and Australia with English, Portuguese, and Spanish translations. The target audience chosen were the medical and allied health professionals involved in the rehabilitation of paediatric CMT. The content was based on the world first "Clinical Practice Guideline for the management of paediatric Charcot-Marie-Tooth disease" [1]. The layout of the Practice Brief was designed according to the criteria for the development of educational materials. The disclosure plan for the Practice Brief involves its publication on University and Hospital websites, www.ClinicalOutcomeMeasures.org and through social media platforms such as ResearchGate, Instagram, Facebook and Twitter, as well as in print format for CMT patient care centres. RESULTS: The English, Portuguese and Spanish versions of the Practice Brief is organised into six sections about assessment, exercise and physical rehabilitation, of which one is focused on progressive resistance exercises for the foot dorsiflexor muscles. CONCLUSION: We developed a Practice Brief in three languages (English, Portuguese and Spanish), synthesising the main recommendations for exercise and related rehabilitative therapies for paediatric CMT from a published clinical guideline.

Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice.

Numerous factors can contribute to the incidence or exacerbation of peripheral neuropathy induced by oxaliplatin (OXA). Recently, platinum accumulation in the spinal cord of mice after OXA exposure, despite the efficient defenses of the central nervous system, has been demonstrated by our research group, expanding the knowledge about its toxicity. One hypothesis is platinum accumulation in the spinal cord causes oxidative damage to neurons and impairs mitochondrial function. Thus, the main aim of this study was to investigate the relationship between aging and OXA-induced neuropathic pain and its comorbidities, including anxious behavior and cognitive impairment. By using an OXA-induced peripheral neuropathy model, platinum and bioelement concentrations and their influence on oxidative damage, neuroprotection, and neuroplasticity pathways were evaluated in Swiss mice, and our findings showed that treatment with OXA exacerbated pain and anxious behavior, albeit not age-induced cognitive impairment. Platinum deposition in the spinal cord and, for the first time, in the brain of mice exposed to OXA, regardless of age, was identified. We found that alterations in bioelement concentration, oxidative damage, neuroprotection, and neuroplasticity pathways induced by aging contribute to OXA-induced peripheral neuropathy. Our results strive to supply a basis for therapeutic interventions for OXA-induced peripheral neuropathy considering age specificities.

Ciprofloxacin's Structure Causing Fluoride-Related Toxicity: A Case Report.

BACKGROUND: Ciprofloxacin is a fluoroquinolone antibiotic widely used in clinical practice with a fluorine atom in its chemical structure. Like other antibiotics, it can induce several adverse effects, such as tendinopathy, musculoskeletal toxicity, peripheral neuropathy, and cardiotoxicity, thereby causing relevant and irreversible health injuries. Ciprofloxacin fluoride's adverse toxicological effect associated with a urinary fluoride concentration above the reference value has not yet been reported. OBJECTIVE: This case report aimed to provide evidence of ciprofloxacin treatment intoxication, an antibiotic containing a fluorine atom in its chemical structure, associated with a fluoride urine concentration above the reference value. CASE PRESENTATION: A 32-year-old man developed tendinopathy and peripheral neuropathy on the third day's night after initiating the ciprofloxacin doses, exhibiting symptoms comparable to a low-power electrical discharge and very intense motor agitation. After following habitual laboratory exams, a urinary fluoride measurement was performed by an ion-selective electrode. The urinary fluoride concentration was above the reference values in mg/g of creatinine. CONCLUSION: This is the first study that has described an association among ciprofloxacinfluoride, tendinopathies, and peripheral neuropathy. The patient's symptomatology has suggested a toxic effect related to fluoride. We consider the documented finding of a fluorine atom at the ciprofloxacin structure and its toxic potential neuropathies and tendinopathies as an issue of alert.

Guillain-Barré syndrome in a 63-year-old patient possibly triggered by ehrlichiosis. Case report.

Guillain-Barré syndrome is an immune-mediated acute demyelinating polyradiculoneuropathy, characterized by progressive flaccid weakness, triggered mainly by respiratory and gastrointestinal infections. We present the case of a 63-year-old male patient with a history of Ehrlichia infection, who consulted the internal medicine emergency department for lower back pain and progressive lower limb paresthesia, accompanied by decreased lower limb strength and nerve conduction velocity test, with results compatible with acute demyelinating sensorimotor polyradiculoneuropathy. To the best of our knowledge, this is the first documented case in Honduran medical literature; in our research, no other cases were found in Latin America or Europe. The importance of the topic and its dissemination in countries where Ehrlichia infection exists is that when cases of Guillain-Barré syndrome that cannot be associated with previous gastrointestinal or respiratory infection, they could be attributed to Ehrlichia infection as a possible cause; therefore, exhaustive preventive measures can be established regarding the transmitting vector of ehrlichiosis.

Anti-synthetase and myelodysplastic syndromes with deep morphea: an example of shared immunopathogenesis? A case-based review.

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient.

The Landscape of Products for Diabetic Peripheral Neuropathy: A Scientific and Patent Systematic Review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a complication of diabetes that occurs in 40 - 60 million individuals worldwide and is associated with other chronic diseases. However, there are no review studies that present the state-of- the- art and technologies developed to circumvent this important health problem. MATERIAL AND METHODS: This review was conducted based on scientific papers and patents. The papers were retrieved from Lilacs, PubMed, and Web of Science databases, and the patents from INPI, ESPACENET, WIPO, and GOOGLE PATENTS. Thus, a sample consisting of 14 scientific articles and 667 patents was analyzed. RESULTS: From the analysis of the data, we drew an overview of the development of biomedical technologies for DPN and detected the pioneering spirit of China, the USA, and Japan in the area, with a focus on the treatment of DPN. Based on this, we carried out a SWOT analysis to help direct future efforts in the area, which should focus primarily on developing technologies for prevention, early diagnosis, and, above all, cure of the disease to reduce the important impact of this disease in various sectors of society. CONCLUSION: This study finds a concentration of diabetic peripheral neuropathy products, especially therapeutic drugs, in high-income countries. It highlights the need for global collaboration and strategic focus on therapeutic adherence and preventive strategies to effectively manage DPN.

Combination of acute diabetic neuropathies following intensive glycaemic management.

While acute and monophasic diabetic neuropathy variants are considered relatively uncommon, diabetes mellitus affects over 6% of the global population, with more than 50% experiencing some form of diabetic neuropathy. Treatment-induced neuropathy of diabetes is an iatrogenic, transient neuropathy characterised by small fibre involvement precipitated by rapid glycaemic control. Diabetic lumbosacral radiculoplexus neuropathy is an asymmetric, predominantly motor neuropathy of the lower limbs, typically starting with localised leg pain. We present a 59-year-old man manifesting features of both conditions following a 12.5% decrease in glycated haemoglobin over 3 months.

Ventilación mecánica, tiempo de hospitalización, muertes y discapacidad según las variantes del síndrome de Guillain-Barré: revisión sistemática y metaanálisis / Mechanical ventilation, hospitalization time, deaths and disability according to the variants of Guillain-Barré syndrome: systematic review and meta-analysis

RESUMEN Objetivos. Determinar el requerimiento y tiempo para ventilación mecánica y Unidad de Cuidados Intensivos (UCI), hospitalización y tiempo de hospitalización, muerte y discapacidad de las variantes axonales del Síndrome de Guillain-Barré (SGB) en comparación con la variante aguda desmielinizante en pacientes de todas las edades. Materiales y métodos. Revisión sistemática que incluyó pacientes con SGB; la exposición fueron las variantes axonales y el comparador la polineuropatía desmielinizante inflamatoria aguda (AIDP) los desenlaces fueron el requerimiento y tiempo en ventilación mecánica (VM), requerimiento y tiempo en la UCI, tiempo de hospitalización, discapacidad y muerte. Se utilizó la escala NewCasttle-Ottawa (NOS) para evaluar el riesgo de sesgo. Se realizó un metaanálisis para calcular las diferencias de medias y los riesgos relativos (RR) con sus intervalos de confianza (IC) del 95% utilizando varianzas inversas y modelos de efectos aleatorios. Resultados. De los 3116 artículos encontrados, 46 cumplieron los criterios de selección. El tiempo en VM fue 7,42 días (IC95%: 0,36 a 1,48) y el tiempo de hospitalización fue 3,11 (IC95%: 0,73 a 5,49) días en las variantes axonales. Las variantes axonales tuvieron un RR de 0,47 (IC95%: 0,24 a 0,92) para el requerimiento de VM en adultos, pero en niños fue de 1,68 (IC95%: 1,25 a 2,25). Hubo una alta heterogeneidad estadística. Conclusiones. Las variantes axonales tienen en promedio mayor tiempo de VM y de hospitalización, en total y por subgrupos. Se observó un mayor requerimiento de VM para las variantes axonales en niños; mientras que en los adultos fue menor.

ABSTRACT Objectives. To determine the requirement and time to mechanical ventilation and Intensive Care Unit (ICU), hospitalization and hospitalization time, death and disability of the axonal variants of Guillain-Barré Syndrome (GBS) in comparison with the acute demyelinating variant in patients of all the ages. Materials and methods. The systematic review that included patients with GBS. The exposure variable was the axonal variants and the comparator was acute inflammatory demyelinating polyneuropathy (AIDP). The outcomes were the requirement and time on mechanical ventilation (MV), requirement and time in the ICU, hospitalization time, disability and death. The NewCasttle-Ottawa Scale (NOS) was used to assess risk of bias. A meta-analysis was conducted to calculate mean differences and relative risks (RR) with their 95% confidence intervals (CI) using inverse variances and random effects models. Results. Of the 3116 articles found, 46 met the selection criteria. The time on MV was 7.42 days (95% CI: 0.36 to 1.48) and the hospitalization time was 3.11 (95% CI: 0.73 to 5.49) days for the axonal variants. The axonal variants had a RR of 0.47 (95% CI: 0.24 to 0.92) for the requirement of MV in adults, but it was 1.68 (95% CI: 1.25 to 2.25) in children. There was a high statistical heterogeneity. Conclusions. Axonal variants showed, on average, longer MV and hospitalization time, overall and by subgroups. A high MV requirement was found for axonal variants in children; it was lower for adults.

Prevalence of cardiovascular autonomic neuropathy in an admixed population of patients with type 1 diabetes. Lessons from a pioneer multicentre study in Brazil.

AIMS: To evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) and its associated factors in Brazilian patients with type 1 diabetes (T1D). METHODS: This cross-sectional, multicentre study was conducted in 14 public clinics in ten Brazilian cities. From 1760 patients, 1712 were included (97.3 %): 953 females (55.7 %), 930 (54.3 %) Caucasians, aged 29.9 ±11.9 years and with diabetes duration of 15.4 ± 9.2 years. CAN was evaluated using cardiovascular autonomic reflex tests. RESULTS: The prevalence of CAN was 23.4 %. Multivariable hierarchical logistic regression showed CAN associated with age, smoking, lower socioeconomic status, higher yearly medical appointments, insulin therapeutic regimens, higher levels of HbA1c, total cholesterol, uric acid, diastolic blood pressure and heart rate, presence of retinopathy, diabetic kidney disease and a tendency to be associated with severe hypoglycemia. Lower health-related quality of life was also found in univariate analysis in these patients. CONCLUSIONS: Patients with T1D presented an important prevalence of CAN that was associated with other diabetes-related chronic complications, and also with demographic, clinical and laboratorial traditional risk factors. Considering lack of formal policy, our data could be used for guiding public health approach to awareness and CAN's screening, diagnosis and clinical management in patients with T1D in Brazil.

Insights into Vincristine-Induced Peripheral Neuropathy in Aged Rats: Wallerian Degeneration, Oxidative Damage, and Alterations in ATPase Enzymes.

This study aimed to elucidate vincristine (VCR)-induced peripheral neuropathy in aged rats, a poorly understood neurotoxicity. Both young and old Wistar rats were administered VCR (0.1 mg/kg, intraperitoneally (i.p.)) and compared to age-matched controls (0.9% saline; 10 mg/mL, i.p.). Mechanical (MN) and thermal nociceptive (TN) responses were assessed on days 0, 6, 11, and 17. Locomotor response, cognitive ability, and anxious-like behavior were evaluated on days 14, 15, and 16. Results showed MN and TN responses in both young and old VCR-exposed rats. In old rats, VCR exacerbated MN (on days 6, 11, and 17) and TN (on days 6 and 17) responses. VCR also induced cognitive impairments and anxiety-like behavior. Histological analysis revealed Wallerian degeneration in the spinal cords of VCR-exposed rats accompanied by macrophage migration. Furthermore, VCR increased Ca2+-ATPase activity while inhibiting Na+, K+-ATPase activity in young and old rats. VCR altered the homeostasis of Mg2+-ATPase activity. Lipid peroxidation and nitrite and nitrate levels increased in young and old rats exposed to VCR. This study provides valuable insights into VCR's mechanistic pathways in aged rats, emphasizing the need for further research in this area.

Effect of 28 days treatment of baricitinib on mechanical allodynia, osteopenia, and loss of nerve fibers in an experimental model of type-1 diabetes mellitus.

BACKGROUND: Type-1 diabetes mellitus (T1DM) is associated with numerous health problems, including peripheral neuropathy, osteoporosis, and bone denervation, all of which diminish quality of life. However, there are relatively few therapies to treat these T1DM-related complications. Recent studies have shown that Janus kinase (JAK) inhibitors reverse aging- and rheumatoid arthritis-induced bone loss and reduce pain associated with peripheral nerve injuries, and rheumatoid arthritis. Thus, we assessed whether a JAK1/JAK2 inhibitor, baricitinib, ameliorates mechanical pain sensitivity (a measure of peripheral neuropathy), osteoporosis, and bone denervation in the femur of mice with T1DM. METHODS: Female ICR mice (13 weeks old) received five daily administrations of streptozotocin (ip, 50 mg/kg) to induce T1DM. At thirty-one weeks of age, mice were treated with baricitinib (po; 40 mg/kg/bid; for 28 days) or vehicle. Mechanical sensitivity was evaluated at 30, 33, and 35 weeks of age on the plantar surface of the right hind paw. At the end of the treatment, mice were sacrificed, and lower extremities were harvested for microcomputed tomography and immunohistochemistry analyses. RESULTS: Mice with T1DM exhibited greater blood glucose levels, hind paw mechanical hypersensitivity, trabecular bone loss, and decreased density of calcitonin gene-related peptide-positive and tyrosine hydroxylase-positive axons within the marrow of the femoral neck compared to control mice. Baricitinib treatment significantly reduced mechanical hypersensitivity and ameliorated sensory and sympathetic denervation at the femoral neck, but it did not reverse trabecular bone loss. CONCLUSIONS: Our findings suggest that baricitinib may represent a new therapeutic alternative to treat T1DM-induced peripheral neuropathy and bone denervation.

Unraveling the RAGE-NF-κB pathway: implications for modulating inflammation in diabetic neuropathy through photobiomodulation therapy.

Diabetic peripheral neuropathy (DPN) is a primary complication observed in diabetes that severely affects quality of life. Recent evidence suggests that photobiomodulation (PBM) is a promising therapy against painful conditions and nerve damage. However, the effects of PBM on DPN remains mostly unknown. In the present study, we investigated the efficacy of PBM therapy in modulating proinflammatory cytokine expression in both central and peripheral nervous systems of rats with Streptozotocin (STZ)-induced type 1 diabetes. Male Wistar rats were allocated into control (naïve), diabetic (STZ), and treatment (STZ + PBM) groups. A single intraperitoneal (i.p.) injection of STZ (85 mg/kg) was administered for the induction of diabetes. Animals were subjected to 10 treatment sessions, every other day. The results herein presented indicate that PBM treatment diminishes Receptor for Advanced Glycation End-products (RAGE) and Nuclear Factor Kappa B (NF-Ï°B) expression in peripheral nervous system and suppresses TNF-α expression in central nervous system tissues. Furthermore, PBM-therapy in diabetic rats also induces increased levels of the anti-inflammatory protein IL-10 in both peripheral and central nervous system. Collectively, our findings demonstrate compelling evidence that PBM-therapy modulates cytokine dynamics and influences RAGE/NF-Ï°B axis in a STZ-induced model of type 1 diabetes.

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.

Anethole Prevents the Alterations Produced by Diabetes Mellitus in the Sciatic Nerve of Rats.

Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy.

Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy.

Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07-1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26-100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.

The unexpected silent manifestation of myocardial infarctions in ischemic heart failure patients: Insights from a case-control study.

BACKGROUND: Recent studies show Silent Myocardial Infarction (SMI) as a quite frequent event. However, regarding severe tertiary care patients that frequently present consequences of Coronary Artery Disease (CAD) and Left Ventricular Dysfunction (LVD), the occurrence of this manifestation is unexpected and its associated factors aren't clear in the literature. AIM: To compare clinical, laboratorial, ventricular and angiographic factors between silent and classical presentation of MI in patients with CAD and LVD. METHODS: Patients with multivessel CAD with over 70 % obstructive lesions and LVD with EF less than 35 % were evaluated for MASS VI trial and later included in the present study. The ventricular function and coronary assessment were measured by echocardiography and SYNTAX score, respectively. The population was stratified in a SMI group and Clinically Manifested Myocardial Infarction (CMMI) group based on MI presentation for a comparison of medical parameters. RESULTS: From 132 patients, 47 (35.6 %) were classified as SMI and 85 (64.4 %) as CMMI. No differences were observed between groups regarding age, sex, diabetes mellitus, SYNTAX score, or collateral circulation. Higher proportion of NYHA II classification, inferior wall MI and lower creatinine clearance were found in SMI group. After multivariate analysis, peripheral diabetic neuropathy (OR = 4.6 [1.1‒12.7] p = 0.032) and inferior wall MI (OR = 4.1 [1.5‒11.4] p = 0.007) were significantly associated with SMI. CONCLUSION: Peripheral diabetic neuropathy and inferior wall MI were associated with SMI presentation. Overall, associated factors tend to be similar comparing SMI and CMMI, but in the specific population of diabetic patients with chronic neuropathy a special care should be taken.

Focal slowing of nerve conduction velocity in leprosy patients unveiled through multisegmented nerve analysis.

BACKGROUND AND AIMS: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of M. leprae, particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols. METHODS: Twenty-five patients with confirmed multibacillary leprosy and 14 controls were accessed. A multisegmented NCS protocol (MP) was performed, targeting short segments through the coldest areas, to identify focal areas of slowed conduction velocity. The effectiveness of this multisegmented protocol was compared to the standard protocol (SP) to detect abnormalities. RESULTS: All leprosy patients presented an abnormal study with the MP, contrasting to 19 with the SP. The most frequent NCS pattern was an asymmetric neuropathy with focal slowing of conduction velocity, found in 23 out of 25 leprosy patients. Significant differences favoring the proposed method were observed when comparing the MP with the SP. Notably, the MP increased the sensitivity to detect abnormalities by 122%, 133%, and 257% for the median, peroneal, and tibial nerves, respectively. MP also increases sensitivity to detect focal abnormalities in the ulnar nerve. INTERPRETATION: The MP protocol significantly increases the sensitivity of NCSs to detect neurophysiological abnormalities in leprosy neuropathy.

Factors Associated With Major Lower Extremity Amputations in Diabetic Foot Infections at a County Hospital in Guatemala.

INTRODUCTION: Outcomes from diabetic foot infections (DFIs) at the major referral hospital (Hospital Nacional de San Benito) in El Petén, Guatemala have not been analyzed. We hypothesized that poor diabetic control might be associated with a high rate of major lower extremity amputations (mLEAs; above the ankle). METHODS: We performed a retrospective analysis at Hospital Nacional de San Benito between (8/14 and 6/23) in patients presenting with DFIs. Patients receiving mLEAs were compared with all others (AO = [trans-metatarsal amputations, toe amputations, incision and drainage, and antibiotic treatment]). Interviews surgeons were undertaken to ascertain reasons for index operation choice. Univariable and multivariable analyses were undertaken to determine factors associated with mLEAs. RESULTS: Of 110 patients with DFIs, there were 23 mLEAs (above the knee = 21, below the knee = 2). Age, duration with diabetes, and a prior ipsilateral minor amputation were associated with mLEAs. Multivariable analysis identified white blood cell count as significant for mLEA (odds ratio = 1.5 95% confidence interval [1.0 to 2.5]). Cited reasons for a high rate of above the knee amputation (AKAs) versus below the knee amputation were patient related (advanced disease, patient frailty, and poor compliance), systemic (lack of vascular equipment and knee immobilizer), and surgeon related. CONCLUSIONS: This cohort of patients presented with an average of 15 years with diabetes mellitus and poor adherence to diabetic treatment (40%). Many of these diabetic patients developed a DFI requiring mLEAs (21%), most of which were AKAs (91%). Efforts to minimize the number of AKA versus below the knee amputation require immediate attention. Programs to adhere to DM control and foot care in patients with DM are urgently needed.

Effectiveness of Duloxetine versus Other Therapeutic Modalities in Patients with Diabetic Neuropathic Pain: A Systematic Review and Meta-Analysis.

Objectives: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus (DM) with symptoms like intense pain and impaired quality of life. This condition has no treatment; instead, the pain is managed with various antidepressants, including duloxetine. The aim of this study is to analyze the evidence on the efficacy of duloxetine in the management of DPN. Methods: A systematic search in different databases was conducted using the keywords "diabetic neuropathy", "duloxetine therapy", "neuropathic pain", and "Diabetes Mellitus". Finally, eight studies were included in this meta-analysis. Results: All articles comparing duloxetine at different doses vs. a placebo reported significant differences in favor of duloxetine on pain scales like 24 h Average Pain Severity (standardized mean difference [SMD] = -1.06, confidence interval [CI] = -1.09 to -1.03, and p < 0.00001) and BPI Severity (SMD = -0.70, CI = -0.72 to -0.68, and p < 0.00001), among others. A total of 75% of the meta-analyses of studies comparing duloxetine at different doses showed a tendency in favor of the 120 mg/d dose. There were significant differences in favor of duloxetine when compared to routine care on the Euro Quality of Life (SMD = -0.04, CI = -0.04 to -0.03, and p < 0.00001) and SF-36 Survey (SMD = -5.86, CI = -6.28 to -5.44, and p < 0.00001) scales. There were no significant differences on the visual analog scale (VAS) when comparing duloxetine and gabapentin. Conclusions: Duloxetine appears to be effective in the management of DPN in different pain, symptom improvement, and quality of life scales.

The association of diabetic peripheral neuropathy with cardiac autonomic neuropathy in individuals with diabetes mellitus: A systematic review.

This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM). METHODS: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM. RESULTS: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN. CONCLUSION: The review presents a possible relationship between DPN and CAN, such as in their severity.