Lineamientos para la prevención y el tratamiento de la osteoporosis inducida por glucocorticoides en pediatría / Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in pediatrics

Objetivo. Proporcionar un marco para profesionales de la salud que tratan a pacientes pediátricos bajo terapia con glucocorticoides (GC) y desarrollar recomendaciones para la prevención y el tratamiento de la osteoporosis inducida por GC en la población pediátrica. Métodos. Un panel de expertos en enfermedades óseas y pediátricas generó una serie de preguntas PICO que abordan aspectos relacionados con la prevención y el tratamiento de osteoporosis en pacientes bajo tratamiento con GC. Siguiendo la metodología GRADE, se realizó una revisión sistemática de la literatura, se resumieron las estimaciones del efecto y se calificó la calidad de la evidencia. Luego se procedió a la votación y a la formulación de las recomendaciones. Resultados. Se desarrollaron 7 recomendaciones y 6 principios generales para osteoporosis inducida por GC en población pediátrica. Conclusión. Estas recomendaciones proporcionan orientación para los médicos que deben tomar decisiones en pacientes pediátricos bajo tratamiento con GC.

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC.

Efeito do alendronato, da dexametasona e da associação de ambos sobre a osteoclastogênese: um estudo in vitro / Effect of alendronate, dexamethasone and the association of both on osteoclastogenesis: an in vitro study

Os osteoclastos são células multinucleadas com a função de degradar e reabsorver o tecido ósseo. Medicamentos como o alendronato (um tipo de bisfosfonato nitrogenado) e a dexametasona (glicocorticoide), podem interferir na fisiologia das células clásticas. Enquanto o alendronato (ALN) inativa o osteoclasto, agindo primordialmente sobre o citoesqueleto desta célula, a dexametasona (DEX) pode promover aumento na atividade dessa célula. O objetivo deste estudo foi avaliar os efeitos do ALN, da DEX e da combinação de ambos sobre a osteoclastogênese e ativação desta célula. Primeiramente foi estabelecido protocolo de remoção de smear layer para os discos de osso bovino e na sequência, foi realizada análise em espectrofotômetro para avaliar a concentração de ALN absorvida pelo osso. O substrato ósseo foi capaz de absorver completamente o ALN da solução nas concentrações de 10 e 100 M. O cultivo de osteoclastos foi feito a partir das células da medula óssea de camundongos e estimulados com 1,25 dihidroxivitamina D3 e através de osteoclastos obtidos a partir de células Raw 264.7 estimulados com RANKL. As células foram cultivadas sobre substrato ósseo previamente tratado com ALN e tratadas com DEX a 1 M. Conclui-se que o tratamento com ALN a 10 M não foi capaz de inibir completamente a reabsorção óssea, seja administrado sozinho ou com a DEX. A DEX promoveu aumento na expressão gênica RANKL e redução de OPG, mesmo quando administrada conjuntamente com ALN. Quando utilizado na concentração de 100 M, o ALN reduziu a quantidade de anéis de actina dos osteoclastos e promoveu significativa diminuição na liberação de EVs nestas células.

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Coriorretinopatia de Birdshot: relato de caso e perspectivas sobre o tratamento / Birdshot chorioretinopathy: a case report and perspectives on its treatment

RESUMO A coriorretinopatia de Birdshot é uma uveíte posterior bilateral crônica rara que acomete, preferencialmente, mulheres de meia-idade. O quadro clínico é composto de pouco ou nenhum processo inflamatório de segmento anterior, associado a vitreíte e lesões coriorretinianas ovoides branco-amareladas de característica hiperfluorescente na angiofluoresceinografia e hipofluorescente na angiografia com indocianina verde. O tratamento se dá por meio de corticoides e outras drogas imunossupressoras. Todavia, em alguns casos, a doença é refratária a tal terapêutica, sendo necessário lançar mão de outras drogas, como os agentes biológicos. O presente artigo busca relatar um caso de coriorretinopatia de Birdshot em ajuste de terapia imunossupressora que evoluiu com má resposta às drogas iniciais e bom controle após uso de imunobiológico e discutir as opções terapêuticas disponíveis atualmente.

ABSTRACT Birdshot chorioretinopathy is a rare chronic bilateral posterior uveitis that preferentially affects middle-aged women. The clinical picture is composed of little or no anterior segment inflammatory process, associated with vitritis and yellowish-white ovoid chorioretinal lesions with hyperfluorescent characteristics on fluorescein angiography and hypofluorescent characteristics on green indocyanine green angiography. Treatment is with corticosteroids and other immunosuppressive drugs. However, in some cases, the disease is refractory to such therapy, making it necessary to resort to other drugs such as biological agents. The present article seeks to report a case of Birdshot chorioretinopathy in an adjustment of immunosuppressive therapy that evolved with poor response to the initial drugs and good control after the use of immunobiologicals and discuss the currently available therapeutic options.

Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Una aproximación actualizada hacia el tratamiento de la esclerosis múltiple / An updated approach to the treatment of multiple sclerosis

La presente es una revisión bibliográfica actualizada sobre el manejo de la Esclerosis Múltiple (EM), enfermedad neurológica progresiva de tipo desmielinizante más frecuente a nivel mundial. En Chile, su presentación remitente-recurrente (RRMS) es patología GES, por lo que se vuelve relevante para el médico general y estudiantes del área de la salud reconocer e identificar las terapias disponibles para el control de esta patología. Si bien la EM no es un cuadro frecuente, su sintomatología es alarmante e incapacitante, por lo que, con frecuencia, el primer acercamiento del paciente es a los servicios de urgencia, tornándose necesario contar con nociones básicas sobre el tratamiento y manejo. La presente revisión recopiló artículos publicados entre 2019 y 2023 de distintos motores de búsqueda con énfasis en el tratamiento farmacológico y no farmacológico de esta enfermedad. Además de describir el tratamiento convencional como la inmunomodulación, las terapias biológicas, el soporte con glucocorticoides y los fármacos remielinizantes, se abordan nuevas líneas de investigación prometedoras, como el rol inmunogénico de la microbiota intestinal, la capacidad epigenética de la dieta, estrategias de rehabilitación cognitiva y el potencial uso de cannabinoides para el manejo paliativo del dolor. Se concluye que un tratamiento oportuno con fármacos modificadores de la enfermedad, tanto de primera línea como de segunda, son imprescindibles para el manejo de la EM, sin embargo, la calidad de vida puede verse significativamente acrecentada por la incorporación de estrategias que se encuentran al alcance del médico general y que no requieren de derivación a nivel secundario.

This is an updated bibliographical review on the management of Multiple Sclerosis (MS), the most common progressive neurological disease of demyelinating disorders worldwide. In Chile, its relapsing-remitting presentation (RRMS) is a state-covered illness pathology, so it becomes relevant for the general practitioner and med students to recognize and identify therapies available for the control of this desease. Although MS is not a frequent condition, its symptoms are alarming and disabling, which is why, frequently, the first approach of the patient is to the emergency services, making it necessary to have basic knowledge about treatment and management. The present review compiled articles published between 2019 and 2023 from different search engines with an emphasis on the pharmacological and non-pharmacological treatment of the MS. In addition to describing conventional treatment such as immunomodulation, biological therapies, glucocorticoid support and remyelinating drugs, new promising lines of research are addressed, such as the immunogenic role of the intestinal microbiota, the epigenetic capacity of the diet, strategies on cognition rehabilitation and the potential use of cannabinoids for the palliative management of pain. It is concluded that the classic treatment with disease-modifying drugs, both first-line and second-line, are essential for the management of MS; however, quality of life can be significantly increased by incorporating strategies found at the reach of the general practitioner and do not require referral at a greater complexity center.

Medidas para optimizar cuidados post rinoplastia. Revisión sistemática de la literatura / Measures to optimize rhinoplasty post operative care, systematic review of the literature

Introducción: El cuidado postoperatorio de la rinoplastia ha evolucionado, paralelamente, al desarrollo de la técnica quirúrgica. Existen varias recomendaciones, sin embargo, hay una gran variabilidad interprofesional de las indicaciones post quirúrgicas. Objetivo: Realizar una revisión sistemática de la literatura científica sobre los cuidados post operatorios de la rinoplastia. Material y Método: Para la realización de este estudio se llevaron a cabo búsquedas en PubMed y en Cochrane Database of Systematic Reviews con los perfiles: ([rhinoplasty] AND [post operative care]) y ([rhinoplasty] AND [post surgical care]). Se seleccionaron los artículos publicados en los últimos 10 años, desde 2013 hasta 2023, ambos inclusive. Resultados: Los documentos analizados recogen la evidencia de los diferentes métodos de cuidados post quirúrgicos en rinoplastia. Estos confirman la utilización de corticoides en el período postoperatorio, así como el reposo en 90° y exponen la variabilidad interprofesional que existe en el protocolo postquirúrgico de esta cirugía. Conclusión: El uso de corticoides y el reposo en 90° disminuyen las complicaciones postquirúrgicas de la rinoplastia. Debe existir una clara información sobre lo que el paciente debe esperar post cirugía. El uso de opioides debe ser restringido y la analgesia debe ser multimodal. Es preciso realizar estudios futuros con mayor nivel de evidencia y tener protocolos uniformes para la práctica clínica.

Introduction: The postoperative care of rhinoplasty has evolved along with the development of the surgical technique. There are several recommendations, however there is enormous interprofessional variability of post-surgical indications. Aim: To carry out a systematic review of the scientific literature on rhinoplasty postoperative care. Material and Method: To carry out this study, searches were carried out in PubMed and in the Cochrane Database of Systematic Reviews with the profiles: ([rhinoplasty] AND [post operative care]) and ([rhinoplasty] AND [post surgical care]). Articles published in the last 10 years were selected, from 2013 to 2023, both inclusive. Results: The documents analyzed collect the evidence of the different methods of post-surgical care in rhinoplasty, they confirm the use of corticosteroids in the postoperative period as well as rest at 90° and expose the interprofessional variability that exists in the post-surgical protocol of this surgery. Conclusion: The use of corticosteroids and rest at 90° reduce the post-surgical complications of rhinoplasty. There must be clear information about what the patient should expect post surgery. The use of opioids must be restricted and analgesia must be multimodal. It is necessary to carry out future studies with a higher level of evidence and have uniform protocols for clinical practice.

Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome / 中华儿科杂志

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

Analysis of adverse neonatal outcomes in pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies / 中华妇产科杂志

Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.

The efficacy and safety of glucocorticoid stent implantation compared with oral glucocorticoid during perioperative period in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To compare the perioperative efficacy and safety of postoperative oral glucocorticoid and glucocorticoid stent implantation in patients with chronic rhinosinusitis with nasal polyps（CRSwNP） undergoing functional endoscopic sinus surgery（FESS）. Methods:Sixty patients with bilateral CRSwNP with similar degree of lesions were selected and divided into three groups: conventional surgical treatment group（20 cases）, glucocorticoid stent group（20 cases）, and oral glucocorticoid group（20 cases）. All three groups underwent routine FESS, patients in the sinus glucocorticoid stent group receiving sinus glucocorticoid stent placed in the ethmoid sinuses（one on each side） during surgery, and patients in the oral glucocorticoid group received postoperative oral methylprednisolone at a dose of 0.4 mg/kg per day for 7 days, followed by a tapering of 8 mg per week to 8 mg followed by maintenance therapy for 1 week, for a total of 3-4 weeks. Visual analog scale（VAS） scores were used to evaluate nasal congestion, rhinorrhea, olfaction, and facial pressure symptoms before surgery, as well as at 2, 4, 8, and 12 weeks after surgery. Nasal endoscopic Lund-Kennedy scores were recorded, and adverse reactions such as stent detachment, stent-related allergic reactions, sleep disorders, edema, gastrointestinal symptoms, rash/acne, behavioral/cognitive changes, weight gain, limb pain, and infection risk were documented. Results:The nasal congestion symptom scores at 2, 4, 8, and 12 weeks after surgery were significantly lower than those before operationin all three groups, and the differences were statistically significant（P<0.05）. The sinus glucocorticoid stent group exhibited significantly lower nasal congestion symptom scores at 4 and 8 weeks after surgery compared to the conventional surgical treatment group. The rhinorrhea symptom scores at 2, 8, and 12 weeks after surgery were significantly lower than preoperative scores in all three groups. Additionally, the sinus glucocorticoid stent group had significantly lower rhinorrhea scores than the conventional surgical treatment group at 2 weeks postoperatively. Concerning olfaction, the sinus glucocorticoid stent group showed a significant reduction in scores at 12 weeks postoperatively, while the oral glucocorticoid group exhibited significant improvement starting from 8 weeks after surgery. There were no statistically significant differences in nasal congestion, rhinorrhea, facial pressure, and olfaction scores between the sinus glucocorticoid stent and oral glucocorticoid groups at 2, 4, 8, and 12 weeks postoperatively. Nasal endoscopy scores revealed lower polyp scores and edema at 2, 4, 8, and 12 weeks postoperatively for all three groups compared to preoperative scores. The conventional surgical treatment group exhibited a significant reduction in nasal secretion scores starting from 8 weeks after surgery, while both the sinus glucocorticoid stent and oral glucocorticoid groups showed significant reductions starting from 2 weeks postoperatively, with scores significantly lower than those of the conventional surgical treatment group at 2 weeks. Scab/scar scores in the conventional surgical treatment group significantly decreased from 8 weeks after surgery, while both the sinus glucocorticoid stent and oral glucocorticoid groups exhibited significant reductions starting from 4 weeks. No statistically significant differences were observed in endoscopy scores（including polyps, edema, nasal secretion, scars, and scabs） between the sinus glucocorticoid stent and oral glucocorticoid groups at 2, 4, 8, and 12 weeks postoperatively. Regarding adverse reactions, no postoperative complications related to sinus glucocorticoid stent were observed in the sinus glucocorticoid stent group. In the oral glucocorticoid group,1 patient experienced irritability, and 1 patient experienced weight gain. Conclusion:The glucocorticoid stent implantation has comparable effects to oral glucocorticoid in improving postoperative nasal symptoms, reducing nasal mucosal edema, scar formation, and nasal secretion in patients with CRSwNP undergoing FESS, with a better safety profile.

Clinical effect of Shenfu injection combined with glucocorticoid on patients with acute left heart failure complicated with bronchospasm / 中华危重病急救医学

OBJECTIVE@#To investigate the clinical effect of Shenfu injection combined with glucocorticoid in the treatment of acute left heart failure complicated with bronchospasm.@*METHODS@#A prospective study was conducted.Ninety patients with acute left heart failure complicated with bronchospasm admitted to Huai'an Second People's Hospital from January 2021 to July 2022 were selected and divided into conventional treatment group, hormone therapy group and combined treatment group according to random number table method, with 30 cases in each group. All patients in the 3 groups received basic Western medicine treatment. On this basis, the conventional treatment group was given 0.25-0.50 g aminophylline injection plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 100 mL slow intravenous infusion, 1-2 times a day. In the hormone treatment group, 1 mg of budesonide suspension for inhalation was diluted to 2 mL by 0.9% sodium chloride injection, twice a day, and applied until 48 hours after the pulmonary wheezing disappeared. The combined treatment group was given glucocorticoid combined with Shenfu injection 80 mL plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 250 mL intravenously, once a day. All treated for 1 week. The general data, traditional Chinese medicine (TCM) syndrome score, TCM syndrone efficacy index, acute left heart failure efficacy, bronchospasm efficacy, systolic blood pressure (SBP), mean arterial pressure (MAP), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and safety of the 3 groups were compared. The patients were followed up for 6 months, and the mortality and re-hospitalization rate of the 3 groups were recorded.@*RESULTS@#Among the 90 patients, a total of 83 patients completed the study, excluding the cases dropped due to death and other reasons. There were 29 cases in the combined treatment group, 25 cases in the hormone therapy group and 29 cases in the conventional treatment group. There were no significant differences in age, gender, course of disease, and previous history (history of diabetes, history of hypertension, history of hyperlipidemia) among the 3 groups. Therefore, they were comparable. The difference of TCM syndrome score before and after treatment, TCM syndrome efficacy index of combined treatment group and hormone therapy group were higher than those of conventional treatment group [difference of TCM syndrome score: 15.14±5.74, 13.24±5.75 vs. 10.62±5.87, TCM syndrome efficacy index: (67.84±14.31)%, (59.94±14.26)% vs. (48.92±16.74)%, all P < 0.05], and the difference of TCM syndrome score and TCM syndrome efficacy index of combined treatment group were higher than those of hormone treatment group (both P < 0.05). The total effective rate of acute left heart failure and bronchospasm in the combined treatment group was significantly higher than that in the conventional treatment group (total effective rate of acute left heart failure: 96.55% vs. 75.86%, total effective rate of bronchospasm: 93.10% vs. 65.52%, both P < 0.05). The difference of serum NT-proBNP before and after treatment in combination therapy group and hormone therapy group was significantly higher than that in conventional treatment group (ng/L: 7 922.86±5 220.31, 7 314.92±4 450.28 vs. 4 644.79±3 388.23, all P < 0.05), and the difference of serum NT-proBNP before and after treatment in the combined treatment group was significantly higher than that in the hormone treatment group (P < 0.05). There were no significant differences in SBP difference, MAP difference, mortality and re-hospitalization rate among the 3 groups. No adverse reactions occurred in the 3 groups during treatment.@*CONCLUSIONS@#Shenfu injection combined with glucocorticoid is effective in the treatment of patients with acute left heart failure complicated with bronchospasm. It is superior to glucocorticoid and aminophylline in relieving bronchospasm, reducing NT-proBNP level and improving total effective rate, and has good prognosis and safety.

Diagnostic yield of bronchoscopic rapid on-site evaluation in severe invasive bronchopulmonary aspergillosis / 中华危重病急救医学

OBJECTIVE@#To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available.@*METHODS@#A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA.@*RESULTS@#A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18).@*CONCLUSIONS@#Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.

Effects of glucocorticoid use on survival of advanced non-small-cell lung cancer patients treated with immune checkpoint inhibitors / 中华医学杂志(英文版)

BACKGROUND@#Lung cancer is the second most common cancer worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Patients with NSCLC have achieved great survival benefits from immunotherapies targeting immune checkpoints. Glucocorticoids (GCs) are frequently used for palliation of cancer-associated symptoms, as supportive care for non-cancer-associated symptoms, and for management of immune-related adverse events (irAEs). The aim of this study was to clarify the safety and prognostic significance of glucocorticoid use in advanced patients with NSCLC treated with immune checkpoint inhibitors (ICIs).@*METHODS@#The study searched publications from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese Science and Technology Journal Database up to March 1st, 2022, and conducted a meta-analysis to assess the effects of glucocorticoid use on overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs through the available data. The study calculated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs).@*RESULTS@#This study included data from 25 literatures that were mainly retrospective, with 8713 patients included. Patients taking GCs had a higher risk for tumor progression and death compared with those not taking GCs (PFS: HR = 1.57, 95% CI: 1.33-1.86, P <0.001; OS: HR = 1.63, 95% CI: 1.41-1.88, P <0.001). GCs used for cancer-associated symptoms caused an obviously negative effect on both PFS and OS (PFS: HR = 1.74, 95% CI: 1.32-2.29, P <0.001; OS: HR = 1.76, 95% CI: 1.52-2.04, P <0.001). However, GCs used for irAEs management did not negatively affect prognosis (PFS: HR = 0.68, 95% CI: 0.46-1.00, P = 0.050; OS: HR = 0.53, 95% CI: 0.34-0.83, P = 0.005), and GCs used for non-cancer-associated indications had no effect on prognosis (PFS: HR = 0.92, 95%CI: 0.63-1.32, P = 0.640; OS: HR = 0.91, 95% CI: 0.59-1.41, P = 0.680).@*CONCLUSIONS@#In advanced NSCLC patients treated with ICIs, the use of GCs for palliation of cancer-associated symptoms may result in a worse PFS and OS, indicating that they increase the risk of tumor progression and death. But, in NSCLC patients treated with ICIs, the use of GCs for the management of irAEs may be safe, and the use of GCs for the treatment of non-cancer-associated symptoms may not affect the ICIs' survival benefits. Therefore, it is necessary to be careful and evaluate indications rationally before administering GCs in individualized clinical management.

Increased behavioural problems associated with corticosteroid use in children with nephrotic syndrome: a Southeast Asian perspective

INTRODUCTION@#The study was performed to determine the psychological problems in children with idiopathic nephrotic syndrome (INS) while they were on steroid therapy, as compared to healthy children.@*METHODS@#This prospective cohort study was conducted in a paediatric clinic of a tertiary hospital. Parents of the participants in the INS group and control group (comprising children without chronic illness) completed questionnaires using the Child Behavioural Checklist (CBCL). The CBCL measures a range of age-specific emotional and psychological problems, including internalising and externalising domains. Analyses of the CBCL scores between groups were done using Mann-Whitney U test.@*RESULTS@#A total of 140 children were recruited with an equal number in the INS and control groups. There was a significant difference in the mean total CBCL scores between the INS group and the control group, specifically in the withdrawal, somatic, anxious and aggressiveness subdomains. Similar findings were demonstrated in correlation between total psychological problems and corticosteroid dosage. In the INS group, steroid dose and cushingoid features were found to have a significant positive association with internalising psychological problems.@*CONCLUSION@#Children with INS on corticosteroid treatment showed an increase in internalising and externalising scores, as compared to healthy children.

Research progress on desensitization of hypersensitivity reaction to iodinated contrast media / 浙江大学学报·医学版

Desensitization therapy for iodinated contrast media (ICM) aims to induce drug tolerance in patients with a history of severe allergic reactions to ICM in a short time. Currently, there is no widely accepted consensus on inducing desensitization to avoid severe allergic responses to ICM. The clinically successful cases have shown that prophylactic use of antihistamines and glucocorticoids can increase the desensitization effect; repeatedly desensitizing and gradually increasing the dose can be conducive to establishing better tolerance to ICM. Most desensitization effects, including stress resistance, can endure 24-48 h. The mechanisms of desensitization therapy remain unclear, the initial dose, administration interval and dose gradient are largely based on clinical experiences and the reaction of patients. This article reviews the current research progress on ICM-related allergies, desensitization methods and related mechanisms, as well as the benefits and hazards of desensitization, to provide a reference for desensitization treatment of hypersensitivity to ICM .

Clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis: a retrospective analysis / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG).@*METHODS@#A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups.@*RESULTS@#After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05).@*CONCLUSIONS@#For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

Clinical characteristics and genetic analysis of two children with Familial glucocorticoid deficiency type 1 due to variants of MC2R gene / 中华医学遗传学杂志

OBJECTIVE@#To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene.@*METHODS@#Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed.@*RESULTS@#Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously.@*CONCLUSION@#FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.

Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

Guidelines for diagnosis and treatment of glucocorticoid-induced osteoporosis / 中华内科杂志

Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.

Chronic non-bacterial osteomyelitis with autoimmune hepatitis: a case report and literature review / 中华儿科杂志

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.