Análise epidemiológica das fraturas de mão em um hospital terciário / Epidemiological analysis of hand fractures in a tertiary hospital

Introdução: O trauma de mão constitui uma epidemia, ocorrendo por diversos fatores, como acidentes de trabalho e violência urbana. Isso gera um impacto significativo por ser uma unidade anatômica vulnerável e importante na realização de atividades cotidianas e para o trabalho. Desse modo, faz-se necessária uma avaliação epidemiológica mais aprofundada no que tange, sobretudo, às fraturas de mãos, entendendo sua elevada morbidade. Método: Estudo descritivo e retrospectivo, feito por análise de prontuários de pacientes conduzidos em um hospital terciário no período de janeiro de 2018 a dezembro de 2020. Resultados: Participaram do estudo 290 pacientes, sendo 85,7% do sexo masculino e 14,3% do sexo feminino. 138 indivíduos tinham entre 20 e 39 anos, representando um total de 47,6%. 51,6% eram do interior do estado do Ceará e 48,4% eram da capital. O principal mecanismo de trauma associado às fraturas foram os acidentes de trânsito (36,4%), seguidos por acidentes de trabalho (26,9%) e ferimentos por arma de fogo (14%). Em relação aos ossos fraturados, houve uma acentuada prevalência do acometimento das falangeanas, em todas as faixas etárias, representando 210 pacientes (72,4%). Conclusão: O presente estudo corrobora com os dados presentes na literatura. Desse modo, é evidenciada a repetição de prevalência de faixa etária, principais mecanismos de trauma envolvidos, bem como ossos acometidos nas fraturas de mão.

Introduction: Hand trauma is an epidemic occurring due to several factors, such as work accidents and urban violence. This significantly impacts it as it is a vulnerable and important anatomical unit for daily activities and work. Therefore, a more in-depth epidemiological assessment is necessary regarding hand fractures and understanding their high morbidity. Method: A descriptive and retrospective study was conducted by analyzing the medical records of patients treated in a tertiary hospital from January 2018 to December 2020. Results: 290 patients participated in the study, 85.7% male and 14.3 % female. One hundred thirty-eight individuals were between 20 and 39 years old, representing 47.6%. 51.6% were from the interior of the state of Ceará, and 48.4% were from the capital. The main trauma mechanism associated with fractures was traffic accidents (36.4%), followed by work accidents (26.9%) and firearm injuries (14%). Concerning fractured bones, there was a marked prevalence of phalangeal involvement in all age groups, representing 210 patients (72.4%). Conclusion: The present study corroborates the data present in the literature. In this way, the repetition of the prevalence of age group, main trauma mechanisms involved, as well as bones affected by hand fractures is evidenced.

Strength and Electrical Properties of Cementitious Composite with Integrated Carbon Nanotubes.

The main objective of this work was to study the effects of carbon nanotubes (CNTs) on the strength and electrical properties of cement mortar. Molecular dynamic simulations (MDSs) were carried out to determine the mechanical and electrical properties of a cementitious composite and its associated mechanisms. To model the atomic structure of a calcium silicate hydrate (C-S-H) gel, tobermorite 11Å was chosen. Single-walled carbon nanotubes (SWCNTs) embedded in a tobermorite structure were tested numerically. In particular, it was concluded that a piezoelectric effect can be effectively simulated by varying the concentration levels of carbon nanotubes. The deformation characteristics were analyzed by subjecting a sample to an electrical field of 250 MV/m in the z-direction in a simulation box. The results indicated a progressively stronger converse piezoelectric response with an increasing proportion of carbon nanotubes. Additionally, it was observed that the piezoelectric constant in the z-direction, denoted by d33, also increased correspondingly, thereby validating the potential for generating an electrical current during sample deformation. An innovative experiment was developed for the electrical characterization of a cementitious composite of carbon nanotubes. The results showed that the electrostatic current measurements exhibited a higher electric sensitivity for samples with a higher concentration of CNTs.

Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, ß-NGF, TGF-ß1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated ß-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-ß1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood−brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-ß1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.

Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression.

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis.

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression.

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.

Polymorphisms in HTLV-1 Tax-responsive elements in HTLV-1-associated myelopathy/tropical spastic paraparesis patients are associated with reduced proviral load but not with disease progression.

Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we evaluated polymorphisms in the 5' LTR and the association with PVL and disease progression. HTLV-1 LTR and tax sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5' TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.

Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019.

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development.

OBJECTIVES: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. METHODS: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. RESULTS: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. CONCLUSION: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.

Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection.

Laboratory diagnosis of human T-lymphotropic viruses (HTLV) 1 and 2 infection is performed by serological screening and further confirmation with serological or molecular assays. Thus, we developed a loop-mediated isothermal nucleic acid amplification (LAMP) assay for the detection of HTLV-1/2 in blood samples. The sensitivity and accuracy of HTLV-1/2 LAMP were defined with DNA samples from individuals infected with HTLV-1 (n = 125), HTLV-2 (n = 19), and coinfected with HIV (n = 82), and compared with real-time polymerase chain reaction (qPCR) and PCR-restriction fragment length polymorphism (RFLP). The overall accuracy of HTLV-1/2 LAMP (95% CI 74.8-85.5%) was slightly superior to qPCR (95% CI 69.5-81.1%) and similar to PCR-RFLP (95% CI 79.5-89.3%). The sensitivity of LAMP was greater for HTLV-1 (95% CI 83.2-93.4%) than for HTLV-2 (95% CI 43.2-70.8%). This was also observed in qPCR and PCR-RFLP, which was associated with the commonly lower HTLV-2 proviral load. All molecular assays tested showed better results with samples from HTLV-1/2 mono-infected individuals compared with HIV-coinfected patients, who present lower CD4 T-cell counts. In conclusion, HTLV-1/2 LAMP had similar to superior performance than PCR-based assays, and therefore may represent an attractive alternative for HTLV-1/2 diagnosis due to reduced working time and costs, and the simple infrastructure needed.

Loop-mediated isothermal amplification (LAMP) assay for rapid and accurate confirmatory diagnosis of HTLV-1/2 infection

Laboratory diagnosis of human T-lymphotropic viruses (HTLV) 1 and 2 infection is performed by serological screening and further confirmation with serological or molecular assays. Thus, we developed a loop-mediated isothermal nucleic acid amplification (LAMP) assay for the detection of HTLV-1/2 in blood samples. The sensitivity and accuracy of HTLV-1/2 LAMP were defined with DNA samples from individuals infected with HTLV-1 (n = 125), HTLV-2 (n = 19), and coinfected with HIV (n = 82), and compared with real-time polymerase chain reaction (qPCR) and PCR-restriction fragment length polymorphism (RFLP). The overall accuracy of HTLV-1/2 LAMP (95% CI 74.8­85.5%) was slightly superior to qPCR (95% CI 69.5­81.1%) and similar to PCR-RFLP (95% CI 79.5­89.3%). The sensitivity of LAMP was greater for HTLV-1 (95% CI 83.2­93.4%) than for HTLV-2 (95% CI 43.2­70.8%). This was also observed in qPCR and PCR-RFLP, which was associated with the commonly lower HTLV-2 proviral load. All molecular assays tested showed better results with samples from HTLV-1/2 mono-infected individuals compared with HIV-coinfected patients, who present lower CD4 T-cell counts. In conclusion, HTLV-1/2 LAMP had similar to superior performance than PCR-based assays, and therefore may represent an attractive alternative for HTLV-1/2 diagnosis due to reduced working time and costs, and the simple infrastructure needed.