One year follow-up on a randomized study investigating serratus anterior muscle and pectoral nerves type I block to reduced neuropathic pain descriptors after mastectomy.

Breast cancer is the second most common diagnosed type of cancer in women. Chronic neuropathic pain after mastectomy occurs frequently and is a serious health problem. In our previous single-center, prospective, randomized controlled clinical study, we demonstrated that the combination of serratus anterior plane block (SAM) and pectoral nerve block type I (PECS I) with general anesthesia reduced acute postoperative pain. The present report describes a prospective follow-up study of this published study to investigate the development of chronic neuropathic pain 12 months after mastectomy by comparing the use of general anesthesia alone and general anesthesia with SAM + PECS I. Additionally, the use of analgesic medication, quality of life, depressive symptoms, and possible correlations between plasma levels of interleukin (IL)-1 beta, IL-6, and IL-10 collected before and 24 h after surgery as predictors of pain and depression were evaluated. The results showed that the use of SAM + PECS I with general anesthesia reduced numbness, hypoesthesia to touch, the incidence of patients with chronic pain in other body regions and depressive symptoms, however, did not significantly reduce the incidence of chronic neuropathic pain after mastectomy. Additionally, there was no difference in the consumption of analgesic medication and quality of life. Furthermore, no correlation was observed between IL-1 beta, IL-6, and IL-10 levels and pain and depression. The combination of general anesthesia with SAM + PECS I reduced the occurrence of specific neuropathic pain descriptors and depressive symptoms. These results could promote the use of SAM + PECS I blocks for the prevention of specific neuropathic pain symptoms after mastectomy.Registration of clinical trial: The Research Ethics Board of the Hospital Sirio-Libanes/Brazil approved the study (CAAE 48721715.0.0000.5461). This study is registered at Registro Brasileiro de Ensaios Clinicos (ReBEC), and ClinicalTrials.gov, Identifier: NCT02647385.

Cross-cultural adaptation and content validity evidence of the Brazilian version of the Nociception Coma Scale-revised / Adaptação transcultural e evidência de validade de conteúdo da versão brasileira da Nociception Coma Scale-revised

ABSTRACT BACKGROUND AND OBJECTIVES: There are communication barriers to assess pain in patients with consciousness and cognitive disorders. This study aimed to make the cross-cultural adaptation of the Nociception Coma Scale-Revised (NCS-R) to the Portuguese language and check the validation evidence of the content of the NCR-R Brazilian version in non-communicative patients with consciousness and cognitive disorders. METHODS: This is a methodological study to check the cross-cultural adaptation of the NCR-R, divided into two stages: cross-cultural adaptation and check of the content validity. The cross-cultural adaptation phase included an initial translation, synthesis of translations, back-translation, expert committee, and cognitive debriefing based on Beaton and Price. A second expert committee evaluated the translated and adapted version to check the content validity index RESULTS: The NCS-R scale was translated and cross-culturally adapted, presenting good evidence of content validity with a Content Validity Index of 0.86. CONCLUSION: The NCS-R is translated and transculturally adapted and has good evidence of content validity.

RESUMO JUSTIFICATIVA E OBJETIVOS: Em pacientes com desordens de consciência e distúrbios cognitivos há barreiras de comunicação para a avaliação da dor. O objetivo deste estudo foi realizar a adaptação transcultural da Nociception Coma Scale-revised (NCS-R) para a língua portuguesa e verificar as evidências de validade de conteúdo da versão brasileira da NCS-R em pacientes não comunicativos com desordens de consciência e distúrbios cognitivos. MÉTODOS: Estudo metodológico para adaptação transcultural da NCS-R dividido em duas etapas: adaptação transcultural e verificação da validade de conteúdo. A fase de adaptação transcultural incluiu a tradução inicial, síntese das traduções, retrotradução, comitê de especialista e debriefing cognitivo baseado em Beaton e Price. A versão traduzida e adaptada foi avaliada por um segundo comitê de especialistas para a avaliação do índice de validade de conteúdo. RESULTADOS: A NCS-R foi traduzida, adaptada do ponto de vista transcultural e apresentou boa evidência de validade de conteúdo com Índice de Validade de Conteúdo de 0,86. CONCLUSÃO: A NCS-R encontra-se traduzida e adaptada do ponto de vista transcultural, e possui boa evidência de validade de conteúdo.

Neuroinflammation, Pain and Depression: An Overview of the Main Findings.

Chronic pain is a serious public health problem with a strong affective-motivational component that makes it difficult to treat. Most patients with chronic pain suffer from severe depression; hence, both conditions coexist and exacerbate one another. Brain inflammatory mediators are critical for maintaining depression-pain syndrome and could be substrates for it. The goal of our paper was to review clinical and preclinical findings to identify the neuroinflammatory profile associated with the cooccurrence of pain and depression. In addition, we aimed to explore the regulatory effect of neuronal reorganization on the inflammatory response in pain and depression. We conducted a quantitative review supplemented by manual screening. Our results revealed inflammatory signatures in different preclinical models and clinical articles regarding depression-pain syndrome. We also identified that improvements in depressive symptoms and amelioration of pain can be modulated through direct targeting of inflammatory mediators, such as cytokines and molecular inhibitors of the inflammatory cascade. Additionally, therapeutic targets that improve and regulate the synaptic environment and its neurotransmitters may act as anti-inflammatory compounds, reducing local damage-associated molecular patterns and inhibiting the activation of immune and glial cells. Taken together, our data will help to better elucidate the neuroinflammatory profile in pain and depression and may help to identify pharmacological targets for effective management of depression-pain syndrome.

Recommendations for local-regional anesthesia during the COVID-19 pandemic.

Since the beginning of the COVID-19 pandemic, many questions have come up regarding safe anesthesia management of patients with the disease. Regional anesthesia, whether peripheral nerve or neuraxial, is a safe alternative for managing patients with COVID-19, by choosing modalities that mitigate pulmonary function involvement. Adopting regional anesthesia mitigates adverse effects in the post-operative period and provides safety to patients and teams, as long as there is compliance with individual protection and interpersonal transmission care measures. Respecting contra-indications and judicial use of safety techniques and norms are essential. The present manuscript aims to review the evidence available on regional anesthesia for patients with COVID-19 and offer practical recommendations for safe and efficient performance.

Desde o início da pandemia de COVID-19, muitas questões surgiram referentes à segurança do manejo anestésico de pacientes acometidos pela doença. A anestesia regional, seja esta periférica ou neuroaxial, é alternativa segura no manejo do paciente COVID-19, desde que o emprego de modalidades que minimizam o comprometimento da função pulmonar seja escolhido. A adoção desta técnica anestésica minimiza os efeitos adversos no pós-operatório e oferece segurança para o paciente e equipe, desde que sejam respeitados os cuidados com proteção individual e de contágio interpessoal. Respeito às contraindicações e emprego criterioso das técnicas e normas de segurança são fundamentais. Este manuscrito tem por objetivo revisar as evidências disponíveis sobre anestesia regional em pacientes com COVID-19 e oferecer recomendações práticas para sua realização segura e eficiente.

[Recommendations for local-regional anesthesia during the COVID-19 pandemic]. / Recomendações para realização de anestesia loco­regional durante a pandemia de COVID­19.

Since the beginning of the COVID-19 pandemic, many questions have come up regarding safe anesthesia management of patients with the disease. Regional anesthesia, whether peripheral nerve or neuraxial, is a safe alternative for managing patients with COVID-19, by choosing modalities that mitigate pulmonary function involvement. Adopting regional anesthesia mitigates adverse effects in the postoperative period and provides safety to pati ents and teams, as long as there is compliance with individual protection and interpersonal transmission care measures. Respecting contra-indications and judicial use of safety techniques and norms are essential. The present manuscript aims to review the evidence available on regional anesthesia for patients with COVID-19 and offer practical recommendations for safe and efficient performance.

Recommendations for local-regional anesthesia during the COVID-19 pandemic / Recomendações para realização de anestesia loco-regional durante a pandemia de COVID-19

Abstract Since the beginning of the COVID-19 pandemic, many questions have come up regarding safe anesthesia management of patients with the disease. Regional anesthesia, whether peripheral nerve or neuraxial, is a safe alternative for managing patients with COVID-19, by choosing modalities that mitigate pulmonary function involvement. Adopting regional anesthesia mitigates adverse effects in the post-operative period and provides safety to patients and teams, as long as there is compliance with individual protection and interpersonal transmission care measures. Respecting contra-indications and judicial use of safety techniques and norms are essential. The present manuscript aims to review the evidence available on regional anesthesia for patients with COVID-19 and offer practical recommendations for safe and efficient performance.

Resumo Desde o início da pandemia de COVID-19, muitas questões surgiram referentes à segurança do manejo anestésico de pacientes acometidos pela doença. A anestesia regional, seja esta periférica ou neuroaxial, é alternativa segura no manejo do paciente COVID-19, desde que o emprego de modalidades que minimizam o comprometimento da função pulmonar seja escolhido. A adoção dessa técnica anestésica minimiza os efeitos adversos no pós-operatório e oferece segurança para o paciente e equipe, desde que sejam respeitados os cuidados com proteção individual e de contágio interpessoal. Respeito às contraindicações e emprego criterioso das técnicas e normas de segurança são fundamentais. Este manuscrito tem por objetivo revisar as evidências disponíveis sobre anestesia regional em pacientes com COVID-19 e oferecer recomendações práticas para sua realização segura e eficiente.

TREATMENT OF FINGERTIP INJURIES BY SPECIALISTS IN HAND SURGERY IN BRAZIL.

OBJECTIVE: To verify if there is consensus about the treatment of each type of injury or amputation of the fingertips, and if there is a statistical difference among the treatment options according to the surgeon's length of time in the hand surgery specialty. METHODS: A cross-sectional survey was conducted during the 37th Brazilian Congress of Hand Surgery, when one hundred and twenty questionnaires were randomly distributed. Observing the inclusion and exclusion criteria, ninety completed questionnaires were included. The answers were submitted to descriptive and inferential analysis with a significance level of p <0.05. RESULTS: This study showed agreement of 63.3% for the treatment with statistical difference for dorsal oblique injury less than 1 cm with bone exposure for the VY advancement flap alternative; 46.7% for volar tip oblique injury with bone exposure less than 1 cm for the Cross Finger alternative; 47.8% for oblique thumb volar injury greater than 1 cm with no bone exposure to the Moberg alternative; 54.4% for thumb pulp injury up to 2.5 cm with bone exposure to the Moberg alternative with proximal release, and 92.2% for antibiotic use, for the "cephalexin" alternative. CONCLUSION: There is no consensus regarding the treatment of most types of fingertip lesions, with agreement of 45.4%. When we subdivided by time group of specialty in hand surgery, there was an increase in agreement to 54.5% of the questions per subgroup. Further comparative studies are needed to assess the consensus among surgeons regarding the treatment of fingertip injury. Level of Evidence III; Cross-sectional survey.

OBJETIVO: Verificar se há consenso sobre o tratamento de cada tipo de lesão ou amputação da ponta do dedo e se há diferença estatística entre as opções de tratamento de acordo com o tempo em que o cirurgião atua na especialidade de cirurgia da mão. MÉTODOS: Pesquisa transversal realizada durante o 37° Congresso Brasileiro de Cirurgia da Mão, quando foram distribuídos cento e vinte questionários de forma aleatória. Observando-se os critérios de inclusão e exclusão, noventa questionários respondidos foram incluídos. As respostas foram submetidas a análise descritiva e inferencial com índice de significância de p < 0,05. RESULTADOS: Este estudo apresentou concordância no tratamento com diferença estatística para lesão oblíqua dorsal menor que 1 cm com exposição óssea para a alternativa de retalho de avanço VY com 63,3%; lesão oblíqua volar com exposição óssea menor que 1 cm para a alternativa Cross Finger com 46,7%; lesão oblíqua volar do polegar maior de 1 cm sem exposição óssea para a alternativa Moberg com 47,8%; lesão da polpa do polegar com até 2,5 cm com exposição óssea para a alternativa Moberg com liberação proximal com 54,4% e uso de antibióticos para a alternativa "cefalexina" com 92,2%. CONCLUSÃO: Não há consenso quanto ao tratamento da maioria dos tipos de lesão da ponta do dedo, sendo que houve concordância em 45,4%. Quando subdividimos por grupo de tempo de especialização em cirurgia de mão, verificou-se aumento da concordância para 54,5% das questões por subgrupo. Há necessidade de realização de novos estudos comparativos para avaliarmos o consenso entre os cirurgiões com relação ao tratamento da lesão das pontas dos dedos. Nível de evidência III; Pesquisa transversal.

Treatment of fingertip injuries by specialists in hand surgery in brazil / Tratamento de lesões da ponta dos dedos por especialistas em cirurgia da mão no brasil

ABSTRACT Objective: To verify if there is consensus about the treatment of each type of injury or amputation of the fingertips, and if there is a statistical difference among the treatment options according to the surgeon's length of time in the hand surgery specialty. Methods: A cross-sectional survey was conducted during the 37th Brazilian Congress of Hand Surgery, when one hundred and twenty questionnaires were randomly distributed. Observing the inclusion and exclusion criteria, ninety completed questionnaires were included. The answers were submitted to descriptive and inferential analysis with a significance level of p <0.05. Results: This study showed agreement of 63.3% for the treatment with statistical difference for dorsal oblique injury less than 1 cm with bone exposure for the VY advancement flap alternative; 46.7% for volar tip oblique injury with bone exposure less than 1 cm for the Cross Finger alternative; 47.8% for oblique thumb volar injury greater than 1 cm with no bone exposure to the Moberg alternative; 54.4% for thumb pulp injury up to 2.5 cm with bone exposure to the Moberg alternative with proximal release, and 92.2% for antibiotic use, for the "cephalexin" alternative. Conclusion: There is no consensus regarding the treatment of most types of fingertip lesions, with agreement of 45.4%. When we subdivided by time group of specialty in hand surgery, there was an increase in agreement to 54.5% of the questions per subgroup. Further comparative studies are needed to assess the consensus among surgeons regarding the treatment of fingertip injury. Level of Evidence III; Cross-sectional survey.

RESUMO Objetivo: Verificar se há consenso sobre o tratamento de cada tipo de lesão ou amputação da ponta do dedo e se há diferença estatística entre as opções de tratamento de acordo com o tempo em que o cirurgião atua na especialidade de cirurgia da mão. Métodos: Pesquisa transversal realizada durante o 37° Congresso Brasileiro de Cirurgia da Mão, quando foram distribuídos cento e vinte questionários de forma aleatória. Observando-se os critérios de inclusão e exclusão, noventa questionários respondidos foram incluídos. As respostas foram submetidas a análise descritiva e inferencial com índice de significância de p < 0,05. Resultados: Este estudo apresentou concordância no tratamento com diferença estatística para lesão oblíqua dorsal menor que 1 cm com exposição óssea para a alternativa de retalho de avanço VY com 63,3%; lesão oblíqua volar com exposição óssea menor que 1 cm para a alternativa Cross Finger com 46,7%; lesão oblíqua volar do polegar maior de 1 cm sem exposição óssea para a alternativa Moberg com 47,8%; lesão da polpa do polegar com até 2,5 cm com exposição óssea para a alternativa Moberg com liberação proximal com 54,4% e uso de antibióticos para a alternativa "cefalexina" com 92,2%. Conclusão: Não há consenso quanto ao tratamento da maioria dos tipos de lesão da ponta do dedo, sendo que houve concordância em 45,4%. Quando subdividimos por grupo de tempo de especialização em cirurgia de mão, verificou-se aumento da concordância para 54,5% das questões por subgrupo. Há necessidade de realização de novos estudos comparativos para avaliarmos o consenso entre os cirurgiões com relação ao tratamento da lesão das pontas dos dedos. Nível de evidência III; Pesquisa transversal.

Benefits in radical mastectomy protocol: a randomized trial evaluating the use of regional anesthesia.

Surgery is the first-line treatment for early, localized, or operable breast cancer. Regional anesthesia during mastectomy may offer the prevention of postoperative pain. One potential protocol is the combination of serratus anterior plane block (SAM block) with pectoral nerve block I (PECS I), but the results and potential benefits are limited. Our study compared general anesthesia with or without SAM block + PECS I during radical mastectomy with axillary node dissection and breast reconstruction using evaluations of pain, opioid consumption, side effects and serum levels of interleukin (IL)-1beta, IL-6 and IL-10. This is a prospective, randomized controlled trial. Fifty patients were randomized to general anesthesia only or general anesthesia associated with SAM block + PECS I (25 per group). The association of SAM block + PECS I with general anesthesia reduced intraoperative fentanyl consumption, morphine use and visual analog pain scale scores in the post-anesthetic care unit (PACU) and at 24 h after surgery. In addition, the anesthetic protocol decreased side effects and sedation 24 h after surgery compared to patients who underwent general anesthesia only. IL-6 levels increased after the surgery compared to baseline levels in both groups, and no differences in IL-10 and IL-1 beta levels were observed. Our protocol improved the outcomes of mastectomy, which highlight the importance of improving mastectomy protocols and focusing on the benefits of regional anesthesia.

Avaliação clínica e laboratorial da cetamina transdérmica, do fentanil transdérmico, da clonidina transdérmica ou suas associações na dor lombar crônica / Evaluación clínica y de laboratorio de cetamina transdérmica, del fentanyl transdérmico, de la clonidina transdérmica o de sus asociaciones en el dolor lumbar crónico / The clinical and laboratorial evaluation of transdermal ketamine, fentanyl, clonidine or their combination in chronic low back pain

OBJECTIVES: chronic low back pain may result in central sensitization, with involvement of different receptors. The aim of this study was to evaluate the analgesic action of transdermal (T) ketamine (a NMDA antagonist), clonidine (an x2-agonist), fentanyl (an opioid agonist), or their combination in chronic low back pain. METHODS: after the institutional approval and informed consent signature, 54 patients were prospectively randomized into 6 groups. Each patient had two of the T preparations applied in different arms. The effect of either T ketamine (1 mg/h), T clonidine (25 µg/h) or T fentanyl (25 µg/h), combined with T placebo (CloG, KetG and FenG); or the combination of T ketamine and clonidine (Ket-CloG), T fentanyl and ketamine (Fen-KetG), or T fentanyl and clonidine (Fen-CloG) was searched for pain and adverse effects. Pain was evaluated by: 1) VAS pain scores, and 2) noradrenaline plasma levels at 0-h (just prior to T application), 3- and 6-h after the T application of two medications, by HPLC. RESULTS: clinically, the pain VAS score at 6-h was smaller in comparison to the 0-h in all groups (p<0.02), and lower when compared to the Fen-CloG and Fen-KetG at the 6-h in relation to the administration of each correspondent T drug alone (p<0.05). The laboratorial data revealed that administration of T fentanyl alone (FenG) resulted in plasma noradrenaline decrease at 6-h (p<0.01), while the association of T fentanyl with clonidine resulted in plasma noradrenaline decrease at 3- and 6-h as compared to the others (p<0.01). The combination of both T ketamine and clonidine (Ket-CloG) did not result in a better analgesic profile and resulted in excessive sedation during the evaluation (p<0.02). CONCLUSIONS: all the studied drugs resulted in clinical analgesia (VAS) at 6-h. However, T fentanyl analgesia was corroborated by lower plasma noradrenaline levels at 6-h when applied alone or at 3-h when combined with T clonidine.

OBJETIVOS: a dor lombar crônica pode resultar em sensibilização central, com a participação de diferentes tipos de receptores. O objetivo deste estudo foi avaliar a ação analgésica por via transdérmica (T) do fentanil, cetamina, clonidina ou suas associações para o alívio da dor lombar crônica. MÉTODOS: após aprovação do Comitê de Ética em Pesquisa e assinatura do termo de consentimento livre e esclarecido, 54 pacientes foram avaliados de forma prospectiva, aleatória e duplamente-encoberta, sendo divididos em 6 grupos. Cada paciente recebeu duas preparações por via transdérmica, aplicadas em braços diferentes (T cetamina (1 mg/h), T clonidina (25 µg/h) ou T fentanil (25 µg/h), associados a T placebo (CloG, CetG and FenG); ou a associação de T cetamina e clonidina (Cet-CloG), T fentanil e cetamina (Fen-CetG), ou T fentanil e clonidina (Fen-CloG). A analgesia e a incidência de efeitos adversos foram avaliadas. A analgesia foi avaliada com: 1) VAS-cm, e 2) níveis plasmáticos de noradrenalina às 0-h (antes da aplicação T), 3- e 6-h após a aplicação T, com HPLC. RESULTADOS: clinicamente, os valores de VAS as 6-h foram menores comparados ao tempo de 0-h para todos os grupos (p<0,02), e menores para o Fen-CloG e Fen-CetG às 6-h em relação à administração de cada droga T isolada (p<0,05). A administração de fentanil T (FenG) resultou em diminuição dos níveis de noradrenalina plasmática às 6-h (p<0,01), enquanto a associação de fentanil T com clonidina T resultou em diminuição de noradrenalina plasmática às 3-h e 6-h em comparação aos demais grupos (p<0.01). A combinação de cetamina e clonidina (Cet-CloG) não ofereceu melhor perfil analgésico e resultou em sedação excessiva (p<0,02). CONCLUSÕES: todos os grupos apresentaram melhora clínica (VAS) da dor às 6-h. Entretanto, somente quem recebeu fentanil T apresentou níveis plasmáticos de noradrenalina mais baixos às 6-h (quando combinado com placebo) e às 3-h quando associado à clonidina T.

OBJETIVOS: el dolor lumbar crónico puede resultar en sensibilización central, con la participación de diferentes tipos de receptores. El objetivo de este estudio fue evaluar la acción analgésica por vía transdérmica (T) del fentanyl, cetamina, clonidina o sus asociaciones en dolor lumbar crónico. MÉTODOS: después de la aprobación por el Comité de Ética en Investigación y Consentimiento, 54 pacientes fueron evaluados de forma prospectiva, aleatoria e duplamente-ciego siendo divididos en seis grupos. Cada paciente recibió dos preparaciones por vía transdérmica, aplicadas en brazos diferentes (T cetamina (1 mg/h), T clonidina (25 µg/h) o T fentanyl (25 µg/h), asociados a T placebo (CloG, CetG y FenG); o la asociación de T cetamina y clonidina (Cet-CloG), T fentanyl y cetamina (Fen-CetG), o T fentanyl y clonidina (fen-CloG). La analgesia y la incidencia de efectos adversos fueron evaluadas. La analgesia fue evaluada con: 1) VAS-cm, y 2) niveles plasmáticos de noradrenalina a las 0 hora (antes de la aplicación T), tres y seis horas después de la aplicación T, con HPLC. RESULTADOS: clínicamente los valores de VAS a las seis horas fueron menores comparados a 0 hora para todos los grupos (p<0,02), y menores para el Fen-CloG y Fen-CetG a las seis horas después de la administración de cada droga T aislada (p<0,05). La administración de fentanyl T (Feng) resultó en disminución de los niveles de noradrenalina plasmática a las seis horas (p<0,01). La combinación de cetamina y clonidina (Cet-CloG) no ofreció mejor perfil analgésico y resultó en sedación excesiva (p<0,02). CONCLUSIONES: todos los grupos presentaron mejoría clínica (VAS) del dolor a las seis horas. Sin embargo, solamente quien recibió fentanyl T presentó menores niveles plasmáticos de noradrenalina a las seis horas (cuando combinado con placebo) y a las tres horas cuando asociado con clonidina T.

Statins induce calcium-dependent mitochondrial permeability transition.

Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are used in the treatment of hypercholesterolemic patients to reduce risk of cardiovascular diseases because of their cholesterol lowering action. Other lipid independent protective actions of statins have been reported. However, some adverse side effects have, also, been described. We report, here, that liver mitochondria isolated from hypercholesterolemic LDL receptor knockout mice treated during 15 days with therapeutic doses (100 mg/kg, p.o.) of lovastatin presented a higher susceptibility to develop membrane permeability transition (MPT). In experiments in vitro, lovastatin-induced MPT in a dose-dependent manner (10-80 microM) by a mechanism sensitive to cyclosporin A (cyclophilin sequestrant), dithiothreitol (reducing agent), adenine nucleotide carrier inhibitor (ADP), catalase (H2O2 reductant) and EGTA (calcium chelator). In agreement with the inhibition of the mitochondrial swelling by dithiothreitol, lovastatin, also, decreased the content of total mitochondrial membrane protein thiol groups. Simvastatin had similar effects on mitochondria; however, pravastatin, a hydrophilic statin, had a weaker effect in inducing MPT. In conclusion, statins can act directly on mitochondria either in vivo or in vitro inducing permeability transition, which is a process involved in cell death.