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OBJECTIVE: Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN). METHODS: We performed a systematic review and meta-analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy-proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta-analysis of proportions, meta-regression, and subgroup meta-analysis were performed at 6 and 12 months for all outcomes. RESULTS: Fifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3-31.5), 3.2% (95% CI 2.4-4.0), and 0.2% (95% CI 0.0-0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9-52.3), 12.1% (95% CI 9.3-14.9), and 2.7% (95% CI 0.0-5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose-response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria. CONCLUSION: A higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death.
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Resumen Introducción: Los inhibidores del punto de control inmunológico (IPCi) son utilizados en los últimos años en el tratamiento de neoplasias malignas avanzadas, con ellos se ha logrado un aumento significativo de la supervivencia; sin embargo, su uso se ha asociado a incremento del riesgo de enfermedades autoinmunes. Objetivo: Describir la incidencia y las características clínicas de los pacientes tratados con IPCi que desarrollaron tiroidopatía. Métodos: Se revisaron retrospectivamente los expedientes de todos los pacientes que recibieron IPCi en los últimos tres años y se identificaron aquellos que desarrollaron anomalías tiroideas. Resultados: La prevalencia de tiroiditis fue de 7 %, con una incidencia de 21.4 % pacientes/mes. La mediana del tiempo para el desarrollo de tiroiditis fue de 63 días. La mayoría de los pacientes presentó síntomas leves o moderados y no requirió hospitalización, si bien todos menos uno desarrollaron hipotiroidismo permanente y requirieron terapia de reemplazo hormonal con levotiroxina. Conclusiones: La disfunción tiroidea secundaria a inmunoterapia es una entidad común en nuestra población. El cuadro clínico suele ser leve y no requiere suspender el tratamiento; sin embargo, debido a la alta incidencia de este evento adverso, los médicos no oncólogos deben estar familiarizados con su diagnóstico y tratamiento, para brindar un manejo multidisciplinario.
Abstract Introduction: Immune checkpoint inhibitors (ICI) are a group of drugs that have been used in recent years for the treatment of advanced malignancies such as melanoma, non-small cell lung cancer and other tumors, significantly increasing survival. However, the use of ICI has been associated with an increased risk of autoimmune diseases, with endocrine organs, specifically the thyroid, being highly susceptible to this phenomenon. Objective: To describe the incidence and clinical characteristics of patients treated with ICI who develop thyroid disease. Methods: The medical records of all patients who received ICI treatment within the last three years were retrospectively reviewed, with those who developed thyroid abnormalities being identified. Results: The prevalence of thyroiditis was 7 %, with an incidence of 21.4 % of patients-month. Median time for the development of thyroiditis was 63 days. Most patients had mild or moderate symptoms and did not require hospitalization, although all but one developed permanent hypothyroidism and required hormone replacement therapy with levothyroxine. Conclusions: Thyroid dysfunction secondary to immunotherapy is a common entity in our population. Clinical presentation is usually mild and does not require treatment discontinuation; however, due to the high incidence of these adverse events, non-oncology specialists must be familiar with the diagnosis and treatment of these alterations in order to provide multidisciplinary management.
Assuntos
Humanos , Tireoidite , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Incidência , Estudos Retrospectivos , Inibidores de Checkpoint ImunológicoRESUMO
RESUMEN Introducción: el temido pie diabético es secuela de dos complicaciones crónicas de la diabetes mellitus, la neuropatía periférica y la insuficiencia vascular. Objetivo: evaluar el impacto de la extensión en la aplicación intralesional del fármaco Heberprot-P a pacientes con úlceras del pie diabético en la provincia de Pinar del Río de enero 2012 a mayo del 2014. Métodos: se realizó un estudio de intervención descriptivo, retrospectivo y transversal en pacientes con úlceras del pie diabético tratados con Heberprot-P en el periodo 2012-2014. El universo se constituyó por 2 225 pacientes diabéticos y una muestra de 2 060 con pie diabético. Se empleó la estadística descriptiva mediante frecuencias absolutas y relativas porcentuales. Resultados: predominó la diabetes mellitus tipo 2 (88 %), se incluyeron 20 escenarios para el tratamiento, preferentemente ambulatorio, el 75 % de las atenciones por el aumento del empleo en la atención primaria de salud y en general por años, frecuente el pie diabético neuroinfeccioso (88 %) y el Wagner 2 (64 %), necesitaron una amputación mayor el 0,9 % de los casos. Conclusiones: la extensión en la aplicación del Heberprot-P al pie diabético es beneficiada, pues se cuenta con múltiples escenarios. El adiestramiento del personal médico, de enfermería y podología posibilitó elevar las atenciones ambulatorias en la atención primaria, el diagnóstico precoz de las lesiones, lo que disminuyó los costos y estadías hospitalarias. Se obtuvo el 99,0 % de efectividad y un porciento bajo de amputación; de esta forma se mejora la calidad de vida.
ABSTRACT Introduction: the fear to diabetic foot is a sequela of two chronic complications of diabetes mellitus, peripheral neuropathy and vascular insufficiency. Objective: to assess the impact of the intra-lesion application of Heberprot-P to patients with diabetic-foot ulcers in Pinar de Rio province from January 2012 to May 2014. Methods: an intervention, descriptive, retrospective and cross-sectional study was carried out in patients with diabetic-foot ulcers treated with Heberprot-P in the period 2012-2014. The target group comprised 2 225 diabetic patients and a sample of 2 060 with diabetic foot, using the descriptive statistics by means of absolute frequencies and relative percentages. Results: type-2 diabetes mellitus prevailed (88 %), having 20 health facilities for the treatment, mainly outpatient clinics, 75 % of the consultations were possible due to increased employment in Primary Health Care and generally for years, neuroinfectious diabetic foot (88 %) and Wagner's 2 (64 %) predominated; it was necessary to perform major amputation for 0,9 % of the cases. Conclusions: the extension on the application of Heberprot-P to diabetic foot is beneficial thanks to the multiple health facilities involved in this task along with the training of doctors of medicine, nursing care personnel and podiatrists, making possible the increase of ambulatory care in Primary Health Care and the early diagnosis of the lesions, decreasing at the same time, the costs of the hospital stays, reaching the service to those who needed it, with 99,0 % of effectiveness and a low percentage of amputation, improving the quality of life.
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Resumen: Introducción: La prevalencia del síndrome eutiroideo enfermo en pacientes con sepsis es aproximadamente de 60%; existe poca información sobre su correlación con falla multiorgánica. Objetivo: Estimar la prevalencia del síndrome eutiroideo enfermo (SEE) y correlacionar con la presencia de fallas orgánicas específicas y puntajes de gravedad y desenlaces clínicos. Métodos: Se incluyeron pacientes con diagnóstico de sepsis en una unidad de cuidados críticos durante el periodo comprendido de marzo de 2014 a febrero de 2016; se tomaron variables clínicas y estudios de laboratorio que incluían perfil tiroideo en todos los pacientes. Análisis estadístico: Estadística descriptiva con medidas de frecuencia, tendencia central y dispersión. Se realizaron análisis de supervivencia con modelos de regresión de Cox y curvas de Kaplan-Meier para mortalidad; razones de riesgo e intervalos de confianza de 95%. Un error alfa ajustado menor de 5% a dos colas fue considerado significativo. Se usó la paquetería estadística STATA SE versión 11.1. Resultados: Se incluyó un total de 90 pacientes, 51.1% de sexo femenino, con edad de 71 ± 14.15 años, IMC al ingreso a la UCI de 24.94 ± 5.07 kg/m2. La prevalencia global de SEE es de 61.1%. Los pacientes con SEE presentaron en mayor proporción falla hemodinámica, renal y hematológica, sin alcanzar significancia estadística. En la fases combinadas 2 y 3 de SEE, sí se observó mayor proporción de falla renal: 88 versus 63.3%, RR = 1.8 (IC 95% 1.1-2.6, p = 0.037), así como altas dosis de vasopresores (norepinefrina > 0.1 µg/kg/min) RR = 2.3 (IC 95% 1.063-5.18, p = 0.024) y menor supervivencia, con una mediana en días de 28 (RIQ 19-39) versus 26 (RIQ 13-36), p = 0.7; PCT igual o mayor a 6 en un 65.5 versus 40%, RR = 1.87 (IC 95% 1.1-3.1, p = 0.18), mayor puntaje de SOFA con mediana de 12 (RIQ 8-4) versus 9 (RIQ 7-13) puntos, p = 0.09. Además, peores desenlaces durante la estancia hospitalaria, evaluados por un índice compuesto que incluye mortalidad, necesidad de ventilación mecánica invasiva (VMI), SOFA ≥ 9 con un RR = 1.713 (IC 95% 1.036-2.83, p = 0.05). El análisis de curva ROC detectó el mejor punto de corte de SOFA como predictor de SEE ≥ 11 con sensibilidad 60.0, especificidad 62 LR + 1.6, LR - 0.63, AUC = 0.6. RR = 1.7 (IC 95% 1.024-3.05, p = 0.034). Conclusiones: Los pacientes con SEE presentan mayor elevación de marcadores de inflamación, requerimiento de vasopresores y soporte ventilatorio, compromiso multiorgánico y mortalidad.
Abstract: Introduction: The prevalence of euthyroid sick syndrome in patients with sepsis is approximately 60%; there is little information on its correlation with multiorgan failure. Objective: To estimate the prevalence of euthyroid sick syndrome (ESS) and correlate it with the presence of specific organ failures, severity scores and clinical outcomes. Methods: Patients with diagnosis of sepsis in a critical care unit during the period from March 2014 to February 2016; we registered the clinical variables and laboratory studies, including thyroid function, in all patients. Statistical analysis: Descriptive statistics with frequency measures of central tendency and dispersion. Mortality-survival analysis with Cox regression models and Kaplan-Meier were made, as well as risk ratios and confidence intervals of 95%. A two-tailed adjusted alpha error of less than 5% was considered significant. The statistical package STATA SE version 11.1 was used. Results: Ninety patients were included, 51.1% female, aged 71 ± 14.15 years; the BMI at admission to the ICU was 24.94 ± 5.07 kg/m2. The overall prevalence of ESS was 61.1%. ESS patients presented in greater proportion with hemodynamic, renal and hematologic failure, without reaching statistical significance. In the combined phases 2 and 3 of SEE, a higher proportion of renal failure was observed: 88 vs. 63.3 %, RR = 1.8 (95% CI 1.1-2.6, p = 0.037). High doses of vasopressors (norepinephrine > 0.1 µg/kg/min) RR = 2.3 (95% CI 1.063-5.18, p = 0.024). Lower survival with a median of 28 days (IQR 19-39) versus 26 (IQR 13-36), p = 0.7. PCT greater than or equal to 6 in 65.5 versus 40%, RR = 1.87 (95% CI 1.1-3.1, p = 0.18); higher SOFA score with a median of 12 (IQR 8-4) versus 9 (IQR 7-13) points, p = 0.09. In addition to worse outcomes during hospital stay evaluated by a composite index that included mortality, need for invasive mechanical ventilation (IMV), SOFA ≥ 9 with a RR = 1.713 (95% CI 1.036-2.83, p = 0.05). ROC curve analysis detected the best cut of SOFA as a predictor of ESS ≥11, sensitivity 60.0, specificity 62 LR + 1.6, LR-0.63, AUC = 0.6. RR = 1.7 (95% CI 1.024-3.05, p = 0.034). Conclusions: Patients with ESS have higher markers of inflammation, increased requirement for vasopressors and ventilatory support, as well as elevated multiorgan failure and mortality.
Resumo: Introdução: A prevalência da síndrome do doente eutireoidiano em pacientes com sepse é de aproximadamente 60%, além disso há pouca informação sobre sua correlação com a insuficiência de múltiplos órgãos. Objetivo: Estimar a prevalência da síndrome do doente eutireoidiano (ESS) e correlacionar com a presença de insuficiência orgânica específica, pontuações de gravidade e desenlaces clínicos. Foram incluídos pacientes diagnosticados com sepse em uma unidade de terapia intensiva durante o período de março de 2014 a fevereiro de 2016, se tomaram variáveis clínicas e estudos laboratoriais que incluiam perfil tireoidiano em todos os pacientes. Análise estatística: Estatística descritiva com medidas de frequência, tendência central e dispersão. Realizaram-se análises de sobrevivência com modelos de regressão de Cox e curvas de Kaplan-Meier para mortalidade. Taxas de risco e intervalos de confiança de 95%. O erro alfa ajustado menor a 5% bicaudal, serão considerados significativos. O programa estatístico STATA versão 11.1. Resultados: Incluiram-se um total de 90 pacientes, 51.1% do sexo feminino, com idades entre 71 ± 14.15 anos, IMC na admissão na UTI foi de 24.94 ± 5.07 kg/m2. A prevalência global de ESS foi de 61.1%. Os pacientes com ESS apresentaram maior proporção de alteração hemodinâmica, renal e hematológica sem alcançar significância estatística. Nas fases 2 e 3 combinadas de ESS se observou maior proporção de insuficiência renal 88 versus 63.3%, RR = 1.8 (IC 95%1.1-2.6, p = 0.037). Altas doses de vasopressores (norepinefrina > 0.1 µg/kg/min) RR = 2.3 (IC 95% 1.063-5.18, p = 0.024). Menor sobrevida com uma média em dias de 28 (IQR 19-39) vs 26 (RIQ 13-36), p = 0.7. PCT igual ou maior a 6 em um 65.5 vs 40%, RR = 1.87 (IC de 95% 1.1-3.1, p = 0.18) maior pontuação SOFA com uma média de 12 (RIQ 8-4) vs 9 (RIQ 7-13) pontos, p = 0.09. Ademais com piores desenlaces durante a estadia hospitalar avaliada por um índice de composto que inclui a mortalidade, a necessidade de VMI, SOFA ≥ 9 com um RR = 1.713 (IC 95% 1.036-2.83, p = 0.05). A análise da curva ROC detectou o melhor ponto de corte de SOFA como um preditor de ESS ≥ 11 sensibilidade 60.0, especificidade 62 LR + 1.6, LR-0.63, AUC = 0.6. RR = 1.7 (IC de 95% 1.024-3.05, p = 0.034). Conclusões: Os pacientes com ESS apresentam maior elevação dos marcadores inflamatórios, maior necessidade de vasopressores, suporte ventilatório, compromisso múltiplo de órgãos e mortalidade.
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Resumen: Introducción: El método simplificado de Fencl-Stewart puede ser empleado a la cabecera del paciente y es más exacto para la evaluación del balance ácido-base. Omron desarrolló un modelo fisicoquímico del cambio en el exceso de base posterior a la infusión de cristaloides con diferencia de iones fuertes (DIF) diferente; sin embargo, fue un trabajo experimental bajo condiciones controladas. Objetivo: Describir el cambio en el estado ácido-base inicial y a las 24 horas en personas críticamente enfermas tras la infusión de siete diferentes tipos de soluciones balanceadas. Material y métodos: Se realizó un estudio retrospectivo, observacional y descriptivo en una terapia intensiva de tercer nivel. Se incluyeron individuos mayores de 18 años de enero de 2015 a julio de 2016. Se evaluaron los efectos en el estado ácido-base a través del modelo fisicoquímico de Fencl-Stewart modificado al inicio y a las 24 horas de la infusión de cristaloides balanceados con DIF de 27 a 154 mEq/L. Se analizaron los gases arteriales a través del gasómetro ABL800 Flex y GEM Premier 3500. El análisis de electrolitos séricos se realizó a través de Architec plus c16,000. El análisis estadístico fue descriptivo a través del programa SPSS v21.0. Resultados: Se incluyeron 198 sujetos. Las soluciones utilizadas con mayor frecuencia fueron Hartmann y H25, en 27.8 y 26.3%, respectivamente. En general, al analizar la totalidad de la población estudiada, todos los parámetros relacionados con acidosis metabólica tuvieron mejoría a las 24 horas. Conclusiones: El uso de soluciones con DIF > 24 mEq/L mejora el estado ácido-base, sin mayor incidencia de hipercloremia a las 24 horas.
Abstract: Introduction: Acid-base status in a body fluid is physically determined by several independent variables. These are: pCO2, the «strong ion difference¼ (SID), all the strong anions (among them is Cl-), and concentrations of nonvolatile weak acids (ATOT). Normal acid-base status is achieved when the independent variables have normal (empirically established) values. The simplified Fencl-Stewart's method can be used at the bedside of the patient and is more accurate in the assessment of acid-base balance. Omron developed a physicochemical model of the projected change in standard base excess (SBE) as a consequence of infused crystalloid solutions of common use (isotonic saline and balanced fluids); unfortunately this was a clinical simulation at standard physiological state. In addition, Kaplan evaluated acid-base balance after the administration of balanced fluids in trauma patients. Nevertheless, to our knowledge, there are no other clinical trials that evaluate the administration of other types of balanced fluids. Objective: To assess the acid-base status of critically ill patients after the infusion of seven different types of balanced solutions. Material and methods: This was a retrospective, observational and descriptive study conducted in an intensive care unit of a tertiary care hospital. We included all patients 18 years and older admitted to this department from January 2015 to July 2016. We evaluated the effects on acid-base balance after the infusion of seven different solutions: 1) Hartmann + 17.8 mEq/L sodium bicarbonate (NaHCO3) (SID 45.8), 2) Hartmann + 8.9 mEq/L NaHCO3 (SID 36.9), 3) Hartmann + 15 mEq/L NaHCO3 (SID 43), 4) Hartmann + 25 mEq/L NaHCO3 (SID 53), 5) Hartmann (SID 28), 6) normal saline 0.45% + 77 mEq/L NaHCO3 (SID 75), and 7) dextrose solution 5% + 154 mEq/L NaHCO3 (SID 154). Arterial blood gases, serum electrolytes, and proteins were measured in the same blood sample. Also SIDa, SEDe, SIG, ATOT, pCO2, change in standard base excess (SBE), pH, [HCO3], [Na]p and SOFA were calculated. pH, SBE and pCO2 were estimated with the ABL8000 FLEX blood gas analyzer. Data are mean ± SD or percents. We used the data analysis package SSPS. Results: One hundred ninety-eight patients were included. Of these, 54% were women and 45% men. The solutions most used were Hartmann (25%), Hartmann + 8.9 mEq/L NaHCO3 (21%), and Hartmann + 25 mEq/L NaHCO3 (18%). Before the infusion, SIDe was under 30 mEq/L in 30% of the patients and above in 23% of them. The effect on the SIDe was significant before the infusion of different solutions (p 0.01), SIDe > 30 ± 8 mEq/L. No metabolic alkalosis or greater decrease of SIDa/SIDe was observed. Conclusions: This study assesses additional varieties of fluids that have a different SID in the clinical setting. No major acid-base disturbances were observed.
Resumo: Introdução: O método simplificado de Fencl-Stewart pode ser usado no leito do paciente e é mais preciso para a avaliação do equilíbrio ácido-básico. Omron desenvolveu um modelo físico-químico da mudança do excesso de base após a infusão de cristalóide com DIF diferente; No entanto, foi um estudo experimental sob condições controladas. Objetivo: Descrever a mudança no estado ácido-básico inicial e às 24 horas em pacientes em estado crítico após a infusão de sete tipos diferentes de soluções equilibradas. Material e métodos: Realizou-se um estudo retrospectivo, observacional e descritivo em uma terapia intensiva. Incluiram-se pacientes maiores de 18 anos de janeiro de 2015 a julho de 2016. Avaliamos os efeitos no estado ácido-básico através do modelo físico-químico de Fencl-Stewart modificado no início e às 24 horas após a infusão de cristalóides equilibrados com DIF 27 a 154 mEq/L. Analizaram-se gases arteriais através do Gasômetro ABL800 Flex e GEM Premier 3500. A análise dos eletrólitos séricos foi feita através de Architec plus C16,000. A análise estatística foi descrita através do programa SPSS v21.0. Resultados: 198 pacientes. As soluções usadas com mais frecuência eram Hartmann e H25, com 27,8 e 26,3%, respectivamente. Em geral, ao analisar toda a população estudada, todos os parâmetros relacionados com acidose metabólica apresentou melhoria às 24 horas. Conclusão: O uso de soluções com DIF 24 mEq/L melhoraram o estado ácido-básico, sem maior incidência de hipercloremia em um intervalo de 24 horas.