Partial repigmentation of vitiligo with tofacitinib, without exposure to ultraviolet radiation

Abstract Vitiligo is a disease that causes macules and achromic and/or hypochromic patches, which can affect from small areas to the entire tegument. Treatment options are few and are generally ineffective. Recently, some case reports have appeared which show positive results with the use of Janus kinase inhibitors associated with phototherapy. This report details the case of a patient with rheumatoid arthritis associated with vitiligo in treatment for two years, whose condition partially improved initially after eight months of oral tofacitinib at a dose of 5 mg twice a day, without exposure to ultraviolet radiation and with continuous improvement during these two years of treatment.

Tofacitinib en el tratamiento de la colitis ulcerosa: casos clínicos / Tofacitinib for the treatment of ulcerative colitis: report of two cases

Biological therapy dramatically changed the management of Ulcerative Colitis (UC). However, a significant number of these patients fail to respond or have secondary loss of response to this strategy. In this clinical situation, the options include intensification of anti-TNF therapy, the use of a second anti-TNF or being switched to another drug class. Among the later, tofacitinib, an oral small molecule directed against the JAK/STAT pathway, is safe and effective in inducing and maintaining remission in patients with moderate-severe UC. We report two patients with UC refractory to conventional treatment and biological therapy, who responded successfully to the use of tofacitinib.

Tratamiento con tofacitinib en adolescentes con alopecia areata / Tofacitinib as a treatment of alopecia areata in adolescents

Resumen Introducción: Actualmente no existe un tratamiento estandarizado para la alopecia areata (AA) grave. Se han reportado numerosos casos exitosos del uso de tofacitinib; sin embargo, no existen publicaciones en México. En este trabajo se reportan cuatro casos de pacientes mexicanos con AA grave tratados con tofacitinib oral. Métodos: Serie de casos de adolescentes con alopecia grave tratados con tofacitinib oral. Para determinar la respuesta al tratamiento se utilizó la Escala de gravedad de alopecia (Severity of alopecia tool). Resultados: Se incluyeron cuatro pacientes de entre 13 y 19 años con AA. En todos los casos se observó crecimiento de cabello y disminución de la gravedad de la alopecia después del tratamiento con tofacitinib. En dos pacientes se observó una respuesta intermedia (del 51 al 90%), y en los otros, moderada (del 6 al 50%), sin efectos adversos serios. Las limitaciones del estudio fueron el tamaño reducido de la muestra y la naturaleza retrospectiva de la recolección de los datos. Conclusiones: El tofacitinib demostró ser una buena alternativa de tratamiento para la AA, total y universal, refractarias a otras terapias.

Abstract Background: Currently, no standardized treatment for severe alopecia areata (AA) exists. Numerous successful cases of the use of tofacitinib have been reported in the world literature, but not in Mexico. Four Mexican adolescents with severe AA treated with oral tofacitinib are reported in the present work. Methods: Series of cases of adolescents with severe AA treated with oral tofacitinib. The severity of alopecia tool was used to determine the response to treatment. Results: Four patients from 13 to 19 years old, were included. In all cases, hair growth was observed, and the alopecia severity decreased after the treatment with tofacitinib. In two patients, an intermediate response (from 51 to 90%) was observed; in the other, a moderate response (from 6 to 50%) was observed, without serious adverse effects. The limitations of the study were the small sample size and the retrospective nature of data collection. Conclusions: Tofacitinib showed to be a good treatment alternative for AA, total and universal, refractory to other therapies.

Rare complications of multikinase inhibitor treatment

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.

Uso do tofacitinibe na retocolite ulcerativa refratária ao tratamento com anti-TNF e anti-integrina / Tofacitinib in the management of ulcerative colitis refractory to anti-tnf and anti-integrin therapies

ABSTRACT Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn's disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.

RESUMO Os inibidores das Janus kinases (JAK) têm sido incorporados ao tratamento de doenças imunomediadas, como artrite reumatoide e, além disso, têm sido testados no tratamento da psoríase e doenças inflamatórias intestinais, tanto na retocolite ulcerativa quanto na doença de Crohn. Tofacitinibe é uma droga do grupo das pequenas moléculas de uso oral que inibe as Janus kinases 1 e 3 e, em menor grau, a Janus kinases 2. Esta inibição promove o bloqueio de uma série de citocinas pró-inflamatórias que estão envolvidas na patogênese das doenças inflamatórias intestinais e desempenham importante papel nos processos imunes, tais como ativação, função e proliferação linfocitária. Nesta presente comunicação, relatamos um caso de um paciente portador de retocolite ulcerativa refratária a três agentes biológicos (infliximabe, adalimumabe e vedolizumabe), com diferentes mecanismos de ação, que recusou o tratamento cirúrgico, porém, apresentou boa resposta com o uso de tofacitinibe, com remissão clínica e endoscópica. Não foram evidenciados efeitos colaterais com a droga. O presente caso ilustra as dificuldades que podemos enfrentar em relação à identificação da expressão do correto mecanismo de ação envolvido na patogênese dos pacientes com retocolite ulcerativa e a importância de um novo agente terapêutico com diferente mecanismo de ação, como o tofacitinibe.

The NK1 receptor antagonist NKP608 inhibits proliferation of human colorectal cancer cells via Wnt signaling pathway

BACKGROUND: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism. METHODS: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot. RESULTS: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, ß-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3. CONCLUSIONS: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/ß-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.

Opioids and immunosupression in oncological postoperative patients / Opioides e imunossupressão em pacientes oncológicos pós-cirúrgicos

Summary Introduction: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU)-acquired infection after a schedule of sedoanalgesia of at least 6 days. Method: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks) were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. Results: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068). Conclusion: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

Resumo Introdução: Recentes pesquisas utilizando animais demonstraram efeitos imunossupressores depois da suspensão de opiáceos, associados a um maior risco de infecção nosocomial. O objetivo desta investigação foi determinar o impacto da interrupção do opioide remifentanilo em uma Unidade de Reanimação Pós-cirúrgica (URP) nas infecções associadas aos cuidados da saúde depois de uma pauta de sedoanalgesia de ao menos 6 dias. Método: Foram relacionados de forma consecutiva todos os pacientes maiores de 18 anos com internação na unidade superior a 4 dias. A população investigada foi aquela afetada por patologia cirúrgica de qualquer origem, na qual a sedação esteve baseada em qualquer hipnótico e como analgésico, foi utilizado o opioide remifentanilo durante pelo menos 96 horas em perfusão contínua. Foram excluídos os pacientes que faleceram durante a internação na unidade e aqueles com analgesia combinada (bloqueios periféricos ou neuroaxiais). Foi realizada uma análise bivariante para determinar fatores de risco para a infecção adquirida na unidade. Foi realizada uma investigação comparativa entre períodos dos 6 dias anteriores e posteriores à interrupção de remifentanilo. Utilizamos o teste de amostras pareadas e a prova de McNemar para as variáveis quantitativas e categóricas, respectivamente. Resultados: O número de pacientes internados na URP durante o período de investigação foi de 1.789. Depois de aplicar os critérios de inclusão e exclusão, a população elegível ficou constituída por 102 pacientes. A densidade de incidência de infecção de forma global foi de 38 por cada 1.000 dias de internamento. A pneumonia associada à ventilação mecânica foi a infecção adquirida mais frequente e Pseudomona aeruginosa, o micro-organismo mais frequentemente isolado. A mortalidade hospitalar foi de 36,27%. Não foram observadas diferenças estatisticamente significativas na incidência de IACS em pacientes oncológicos em relação à descontinuação de remifentanilo (p=0,068). Conclusão: O estado basal de imunossupressão dos pacientes oncológicos não implica uma maior incidência de IACS em relação à interrupção do remifentanilo. Seria interessante a realização de uma investigação multicêntrica de URP que incluísse padrões imunológicos.

Medullary thyroid carcinoma - Adverse events during systemic treatment: risk-benefit ratio

ABSTRACT Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular C cells of the thyroid and associated with mutations in the proto-oncogene REarranged during Transfection (RET). The prognosis of MTC depends on clinical stage, with a 95.6% 10-year survival rate among patients with localized disease and 40% among patients with advanced disease. Standard chemotherapy and radiotherapy have no significant impact on the overall survival of these patients and two tyrosine kinase receptor inhibitors (TKIs), vandetanib and cabozantinib, have been recently approved for the systemic treatment of locally advanced or metastatic MTC. However, since patients with MTC and residual or recurrent disease may have an indolent course with no need for systemic treatment, and since these drugs are highly toxic, it is extremely important to select the patients who will receive these drugs in a correct manner. It is also essential to carefully monitor patients using TKI regarding possible adverse effects, which should be properly managed when occurring.

Descripción de la Cronología del Dolor de las Contracciones Uterinas para Analgesia del Trabajo de Parto, una tarea pendiente / Description of the chronology of the pain of uterine contractions for analgesia of labor, a pending task

Propósito: Describir la periodicidad del momento de máxima intensidad del dolor de las contracciones uterinas (CUs) durante el trabajo de parto (TDP) para eventualmente permitir el desarrollo de nuevos modelos de administración de analgesia endovenosa. Material y método: Embarazadas de término en TDP, reclutadas desde marzo 2014 por 18 meses, de manera no probabilística consecutiva. Se obtuvo el momento de máximo dolor por autoreporte de las pacientes con cronómetros, previa capacitación. Análisis: Regresión para medidas repetidas de efectos mixtos a los 3-5, 6-7 y 8-10cm de dilatación. La variable respuesta es el intervalo de tiempo desde el momento de máximo dolor de la CU basal al de la contracción siguiente. Resultados: En 64 pacientes, se obtuvo 5 intervalos de tiempo. Para la dilatación de 3-5cm una mediana=140.92 segundos y los coeficientes de regresión (CR) en 4 intervalos de tiempo con respecto al basal de 4.2, 15.9, -2.7 y -5.8 segundos. Para 67cm una mediana=131.16 seg y CR 13.4, 11.3, 2 y -10 seg. Para 8-10cm una mediana=129.3 seg y CR -6.7, 0.49, -2.5 y -7.7 seg. No hubo diferencias significativas entre los coeficientes de regresión. Conclusiones: Con los datos obtenidos podemos señalar que no hubo diferencias estadísticas significativas entre los intervalos de tiempo de los momentos de máximo dolor durante el TDP en fase activa. Esta información es relevante para apoyar el desarrollo de un modelo predictivo del dolor.

Aim: To describe the timing of the moment of maximum intensity of uterine contraction (UC) pain in labor to possibly enable the development of new models for administering endovenous analgesia. Materials and Methods: Full-term pregnant women in labor, recruited from March 2014 for 18 months, using consecutive nonprobability sampling. The moment of maximum pain was ascertained as self-reported by patients previously trained with chronometers. Analysis: Regression for repeated measurements from mixed results at 3-5, 6-7 and 8-10cm of dilation. The response variable was the time interval from the moment of maximum pain of the baseline UC to the following contraction. Results: In 64 patients, 5 time intervals were obtained. For the dilation of 3-5cm, a median=140.92 seconds and regression coefficients (RC) in 4 time intervals relative to the baseline of 4.2, 15.9, -2.7 and -5.8 seconds. For 6-7cm, a median =131.16 sec and RC 13.4, 11.3, 2 and -10 sec. For 8-10cm, a median =129.3 sec and RC -6.7, 0.49, -2.5 and -7.7 sec. There were no significant differences among the regression coefficients. Conclusions: With the data collected we can report that there were no statistically significant differences between the time intervals of the moments of maximum pain during active labor. This information is relevant to support the development of a predictive model for this pain.

Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite)

ABSTRACT Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7.5 µg/mL) induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

Rimonabant improves metabolic parameters partially attributed to restoration of high voltage-activated Ca2+ channels in skeletal muscle in HFD-fed mice

Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising strategies for the treatment of obesity and other related metabolic disorders. Although CB1R inhibition may cause adverse psychiatric effects including depression and anxiety, the investigation of the role of peripheral CB1R on weight loss and related metabolic parameters are urgently needed. We first explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist, on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice. Then, real-time PCR and electrophysiology were used to explore the contribution of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD feeding caused body weight gain, and decreased glucose/insulin tolerance in mice compared to those in the regular diet group (P<0.05), which was restored by rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the control group. Daily treatment with rimonabant for 5 weeks was shown to counter such decrease (P<0.05). Collectively, our findings provided a novel understanding for peripheral CB1R's role in the modulation of body weight and glucose homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as potential targets for obesity treatment.

Anesthesia in pregnant women with HELLP syndrome: case report / Anestesia para gestante com síndrome HELLP: relato de caso

Abstract Background and objectives: HELLP syndrome, characterized by hemolysis, high levels of liver enzyme, and low platelet count, is an advanced clinical stage of pre-eclampsia, progressing to high maternal (24%) and perinatal (up 40%) mortality, despite childbirth care in a timely manner. The goal is to describe the anesthetic management of a case with indication to emergency cesarean. Case report: Female patient, 36 years old, gestational age of 24 weeks, with hypertensive crisis (BP 180/100 mmHg) and severe headache, was admitted to the operating room for a cesarean section after diagnosis of HELLP syndrome. Indicated for general anesthesia, we opted for total intravenous with intubation after rapid sequence induction with propofol and remifentanil in continuous target-controlled infusion, and rocuronium at a dose of 1.2 mg/kg. Maintenance was achieved with propofol and remifentanil. The surgical procedure was uneventful, the child was born with APGAR 1/5 and transferred to the NICU. At the end of surgery, the patient was extubated in the operating room and taken to the ICU. The postoperative period was uneventful with no changes worthy of note and the patient was discharged on the sixth postoperative day. Conclusion: When general anesthesia is the choice in parturient with HELLP syndrome, tracheal intubation with rapid sequence induction due to possible difficult airway, as well as the use of drugs to control the hemodynamic response can minimize the complications associated with the procedure, as occurred in this case.

Resumo Justificativa e objetivos: A síndrome HELLP, caracterizada por hemólise, elevação dos níveis de enzimas hepáticas e plaquetopenia, representa estágio clínico avançado da pré-eclâmpsia, cursando com elevada mortalidade materna (24%) e perinatal (até 40%), apesar da assistência ao parto de forma oportuna. O objetivo é descrever o manejo anestésico de um caso com indicação de cesariana de emergência. Relato de caso: Paciente do sexo feminino, 36 anos, idade gestacional 24 semanas, com crise hipertensiva (PA 180/100 mmHg) e cefaleia intensa, é encaminhada ao Centro Cirúrgico para operação cesariana após diagnóstico de síndrome HELLP. Indicada anestesia geral, optou-se por venosa total com intubação após indução sequencial rápida, com propofol e remifentanil em infusão contínua alvo-controlada e rocurônio na dose de 1,2 mg/kg. A manutenção foi obtida com propofol e remifentanil. O procedimento cirúrgico transcorreu sem anormalidades, a criança nasceu com APGAR 1/5 e foi encaminhada à UTI Neonatal. Ao final da cirurgia, procedeu-se à extubação na sala cirúrgica e a paciente foi encaminhada ao CTI. O pós-operatório decorreu sem alterações dignas de nota e a paciente teve alta no sexto dia pós-operatório. Conclusão: Quando se opta pela anestesia geral em parturiente com síndrome HELLP, a intubação traqueal com técnica de indução sequencial rápida em função de possível via aérea difícil, bem como o emprego de drogas que controlem a resposta hemodinâmica, podem minimizar as complicações associadas ao procedimento, como ocorreu no presente caso.

Randomized double-blind clinical trial comparing two anesthetic techniques for ultrasound-guided transvaginal follicular puncture / Estudo clínico duplo-cego randomizado comparando duas técnicas anestésicas para punção folicular guiada por ultrassom transvaginal

ABSTRACT Objective: To compare the anesthetic techniques using propofol and fentanyl versus midazolam and remifentanil associated with a paracervical block with lidocaine in performing ultrasound-guided transvaginal oocyte aspiration. Methods: A randomized double-blind clinical trial (#RBR-8kqqxh) performed in 61 women submitted to assisted reproductive treatment. The patients were divided into two groups: anesthetic induction with 1mcg/kg of fentanyl associated with 1.5mg/kg of propofol (FP Group, n=32), in comparison with anesthetic induction using 0.075mg/kg of midazolam associated with 0.25mcg/kg/min of remifentanil, and paracervical block with 3mL of 2% lidocaine (MRPB Group, n=29). Main outcome measures: human reproduction outcomes, modified Aldrete-Kroulik index, hemodynamic parameters, and salivary cortisol. Results: The results revealed a higher number of embryos formed in the FP Group (p50=2 versus 1; p=0.025), gestation rate two times higher in the FP Group (44.4% versus 22.2%; p=0.127), less time to reach AK=10 in the MRPB Group (p50=10 versus 2; p<0.001), and lower mean of hemodynamic parameters in the MRPB Group (p<0.05). Conclusion: Anesthesia with fentanyl and propofol as well as with midazolam, remifentanil, and paracervical block offered satisfactory anesthetic conditions when performing assisted reproduction procedures, providing comfort for the patient and physician.

RESUMO Objetivo: Comparar as técnicas anestésicas utilizando propofol e fentanil contra midazolam e remifentanil associados a um bloqueio paracervical com lidocaína na aspiração de oócitos transvaginal guiada por ultrassom. Métodos: Ensaio clínico randomizado duplocego (#RBR-8kqqxh) realizado em 61 mulheres submetidas ao tratamento de reprodução assistida. As pacientes foram divididas em dois grupos: um grupo foi submetido à indução da anestesia com 1mcg/kg de fentanil associada com 1,5mg/kg de propofol (Grupo FP, n=32), em comparação com ao grupo submetido à indução da anestesia utilizando 0,075mg/kg de midazolam associada com 0,25mcg/kg/min de remifentanil, e bloqueio paracervical com 3mL de lidocaína a 2% (Grupo MRBP, n=29). Foram avaliados os resultados reprodutivos, índice modificado de Aldrete e Kroulik, parâmetros hemodinâmicos e cortisol salivar. Resultados: Foi encontrado um número mais elevado de embriões formados no Grupo FP (p50=2 versus 1; p=0,025), taxa de gestação duas vezes mais elevada no Grupo FP (44,4% versus 22,2%; p=0,127), menos tempo para alcançar AK=10 no Grupo MRBP (p50=10 versus 2; p<0,001) e média mais baixa de parâmetros hemodinâmicos do Grupo MRBP (p<0,05). Conclusão: Ambas as anestesias (com fentanil e propofol, e com midazolam, remifentanil e bloqueio paracervical) ofereceram condições anestésicas satisfatórias na realização de procedimentos realizados em reprodução assistida, proporcionando conforto para o paciente e médico.

Incidence of vertebral fractures in calcium and vitamin D-supplemented postmenopausal Brazilian women with osteopenia or osteoporosis: data from Arzoxifene Generations Trial

ABSTRACT Objective Vertebral fracture is the most common osteoporotic fracture, affecting quality of life and increasing mortality. Epidemiological data on incidence of vertebral fracture are scarce in Brazil and throughout Latin America. Our aim was to determine vertebral fracture incidence and risk factors in a female Brazilian population. Subjects and methods Postmenopausal women with low bone mass were studied from the Brazilian placebo group of Arzoxifene Generations Trial (n = 974), followed for up to 5 years. The primary endpoint was new vertebral fractures, detected by X-Ray. Experimental design defined two strata: A. Osteoporosis or previous vertebral fracture with osteopenia; B. Osteopenia without previous fracture. Previous fracture, T-score, ionized calcium, alkaline phosphatase, creatinine and glucose were analyzed at baseline. Crude and adjusted incidence rates of vertebral fractures were estimated and Poisson regression model was used. Results Incidence rate was 7.7 (95% CI of 5.4 to 10.9) per 1,000 person-years (PY), increasing as a function of age. Women with new vertebral fractures had higher prevalence of previous nonvertebral fracture after menopause, were older and had lower lumbar spine (LS) T-score. Fracture risk increased by 46% for each unit reduction in LS T-score. Variables correlated with new vertebral fracture were age (p = 0.034), LS T-score, stratum A (p = 0.001 for both) and previous nonvertebral fracture after menopause (p = 0.019). In the final model, LS T-score was the strongest predictor. Conclusions Incidence rate of vertebral fracture of 7.7 per 1,000 PY. Age and previous fractures were associated with new vertebral fracture, but LS T-score was the most important predictor.

Posicionamento sobre o uso de tofacitinibe no algoritmo do Consenso 2012 da Sociedade Brasileira de Reumatologia para o tratamento da artrite reumatoide / Update on the 2012 Brazilian Society of Rheumatology Guidelines for the treatment of rheumatoid arthritis: position on the use of tofacitinib

Resumo Em 2014, o tofacitinibe, um medicamento modificador do curso da doença (MMCD) sintético, alvo-específico, inibidor seletivo das Janus quinases (JAK), foi aprovado para uso no Brasil. Este documento de posicionamento tem o objetivo de atualizar as recomendações da Sociedade Brasileira de Reumatologia (SBR) sobre o tratamento da artrite reumatoide (AR) no Brasil, especificamente com relação ao uso de MMCD sintéticos alvo-específicos. O método dessa recomendação incluiu revisão bibliográfica de artigos científicos, feita na base de dados Medline. Após a revisão, foi produzido um texto, que responde a perguntas na estrutura Pico, e considera questões de eficácia e segurança do uso do tofacitinibe para tratamento de AR em diferentes situações (como primeira linha de tratamento, após falha ao metotrexato [MTX] ou outros MMCD sintéticos convencionais, após falha da terapia biológica). Com base nas evidências existentes, e considerando os dados disponíveis sobre eficácia, segurança e custo das medicações disponíveis para tratamento da doença no Brasil, a Comissão de AR da SBR, após processo de discussão e votação de propostas, estabeleceu o seguinte posicionamento sobre o uso de tofacitinibe para o tratamento da AR no Brasil: “Tofacitinibe, em monoterapia ou em associação ao MTX, é uma opção para os pacientes com AR em atividade moderada ou alta, após falha de pelo menos dois esquemas com diferentes MMCD sintéticos e um esquema de MMCD biológico”. O grau de concordância com essa recomendação foi 7,5. Esse posicionamento poderá ser revisto nos próximos anos, com a maior experiência adquirida com o uso do medicamento.

Abstract In 2014, tofacitinib, a target-specific, synthetic disease modifying anti rheumatic drug (DMARD) and a selective inhibitor of Janus kinase (JAK) was approved for use in Brazil. This position paper aims to update the recommendations of the Brazilian Society of Rheumatology (SBR) on the treatment of rheumatoid arthritis (RA) in Brazil, specifically regarding the use of target-specific synthetic DMARDs. The method of this recommendation consisted of a literature review of scientific papers held on the Medline database. After this review, a text was produced, answering questions in Pico structure, considering efficacy and safety issues of tofacitinib use for RA treatment in different scenarios (such as first-line treatment after failure with methotrexate [MTX] or other conventional synthetic DMARDs after failure with biological therapy). Based on existing evidence, and considering the available data on efficacy, safety and cost of medications available to treat the disease in Brazil, the RA Commission of SBR, after a process of discussion and voting on proposals, established the following position on the use of tofacitinib for treatment of RA in Brazil: “Tofacitinib, alone or in combination with MTX, is an alternative for RA patients with moderate or high activity after failure of at least two different synthetic DMARDs and one biological DMARD.” The level of agreement with this recommendation was 7.5. This position may be reviewed in the coming years, in the face of a greater experience with the use of this medication.

Remifentanil protects uterus against ischemia-reperfusion injury in rats

PURPOSE: To investigate the effects of remifentanil as an antioxidant and analyze the histopathologic, biochemical changes in experimental ischemia-reperfusion (I/R) exposed rat uteri. METHODS: Wistar albino rats were assigned to three groups (n = 7). 2h period of ischemia was followed by 1h of reperfusion in the I/R and the I/R-remifentanil groups. After ischemia, no drug was administered in the sham and I/R groups. In the I/R-remifentanil group, remifentanil infusion (2 μg/kg/min) was started in the ischemia period, and continued until the end of reperfusion. After the ischemic and reperfusion period, the ischemic uterine horns were removed surgically for biochemical and histopathologic examination. Tissue damage scores (endometrial epithelial glandular leukocytosis, degeneration, and endometrial stromal changes) were examined. Malondialdehyde levels and catalase, superoxide dismutase enzyme activities in tissue were measured. RESULTS: We found significantly lower epithelial leukocytosis and cell degeneration in the I/R-remifentanil group (p<0.05). Remifentanil administration significantly decreased concentrations of malondialdehyde, and increased catalase and superoxide dismutase enzyme activities (p<0.05). CONCLUSION: Remifentanil appears to protect the uterine tissue against ischemia-reperfusion and can be used safely in uterus transplantation.

Ocular risk management in patients undergoing general anesthesia: an analysis of 39,431 surgeries

OBJECTIVE: This study sought to describe and analyze ocular findings associated with nonocular surgery in patients who underwent general anesthesia. METHODS: The authors retrospectively collected a series of 39,431 surgeries using standardized data forms. RESULTS: Ocular findings were reported in 9 cases (2.3:10,000), which involved patients with a mean age of 58.9±19.5 years. These cases involved patients classified as ASA I (33%), ASA II (55%) or ASA III (11%). General anesthesia with propofol and remifentanil was used in 4 cases, balanced general anesthesia was used in 4 cases, and regional block was used in combination with balanced general anesthesia in one case. Five patients (55%) underwent surgery in the supine position, one patient (11%) underwent surgery in the lithotomy position, two patients (22%) underwent surgery in the prone position, and one patient (11%) underwent surgery in the lateral position. Ocular hyperemia was detected in most (77%) of the 9 cases with ocular findings; pain/burning of the eyes, visual impairment, eye discharge and photophobia were observed in 55%, 11%, 11% and 11%, respectively, of these 9 cases. No cases involved permanent ocular injury or vision loss. CONCLUSION: Ophthalmological findings after surgeries were uncommon, and most of the included patients were relatively healthy. Minor complications, such as dehydration or superficial ocular trauma, should be prevented by following systematic protocols that provide appropriate ocular occlusion with a lubricating ointment and protect the eye with an acrylic occluder. These procedures will refine the quality of anesthesia services and avoid discomfort among patients, surgeons and anesthesia staff. .

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.