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.

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.

Características clínico-oftalmológicas y evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social, Paraguay / Clinical-ophthalmological characteristics and evolution of patients with moderately severe active thyroid ophthalmopathy treated with methylprednisolone boluses who attended the Central Hospital of the Instituto de Previsión Social, Paraguay

Introducción: La oftalmopatía tiroidea (OT) es un trastorno debilitante en pacientes con enfermedad tiroidea autoinmune, principalmente enfermedad de Graves, que se desarrolla entre el 30 a 50% de los casos. Objetivos: Describir las características clínico-oftalmológicas y la evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social en el tiempo comprendido entre enero de 2018 y setiembre de 2021. Materiales y métodos: Investigación de diseño observacional, con estudio descriptivo, retrospectivo. Resultados: Se revisaron fichas de 34 pacientes con OT activa moderada severa que recibieron bolos de metilprednisolona basado en las guías EUGOGO 2016, de los cuáles se excluyeron 3 pacientes por tener fichas incompletas y otros 3 pacientes ya que requirieron tratamiento de segunda línea previo al término del esquema de 12 sesiones. De los 28 pacientes estudiados, la edad promedio fue de 43,6 ±13,1 años, el 89% de sexo femenino y el 28,5%, fumadores. En cuanto a la función tiroidea de la población previo al tratamiento, se constató hipertiroidismo en el 82%, hipotiroidismo en el 11% y eutiroidismo en el 7%; y posterior al tratamiento, se constató hipertiroidismo en el 78,6% (subclínico), eutiroidismo en el 17,9% e hipotiroidismo en el 3,5%. La mayoría (92.6%) contaba con anticuerpos contra el receptor de TSH positivo, con un promedio de 18 ± 9,9 mIU/Ml. Respecto a la actividad de la oftalmopatía según la escala CAS, se constató un promedio de 4,1 ±1,0 previo al tratamiento y posterior 1,2 ±1,4; de ellos el 46,4% presentó un estado leve según escala de gravedad, 39% sin criterios de gravedad y 14 % persistió en moderada -severa. Se constató mejoría de la agudeza visual tras el tratamiento (57,1%), el promedio de exoftalmía previo al tratamiento fue 22,2 mm y posterior 21,1 mm; se presentó diplopía en el 7,1% previo al tratamiento y en el 3,6% posterior al tratamiento. Conclusión: El tratamiento con glucocorticoides endovenosos en la oftalmopatía de Graves moderada-severa (esquema EUGOGO 2016) fue muy efectivo, revirtiendo la actividad y consecuentemente ayudando a disminuir la gravedad, en la gran mayoría de nuestros pacientes. Esto podría explicarse porque la oftalmopatía era incipiente y por el alto grado de adherencia de los pacientes en el contexto de un manejo multidisciplinar bien protocolizado.

Introduction: Graves' orbitopathy (GO) is a debilitating disorder in patients with autoimmune thyroid disease, mainly Graves' disease, which develops in 30 to 50% of cases. Objectives: To describe the clinical-ophthalmological characteristics and evolution of patients with moderate-to- severe active GO treated with methylprednisolone boluses who attended the Central Hospital of the Institute of Social Security between January 2018 and September 2021. Materials and methods: Observational design research, descriptive, retrospective study. Results: Records of 34 patients with active moderate-to-severe GO who received boluses of methylprednisolone based on the EUGOGO 2016 guidelines, were reviewed, of which 3 patients were excluded due to having incomplete records and another 3 patients since they required second-line treatment prior to end the 12-session scheme. Of the 28 patients studied, the average age was 43.6 ±13.1 years, 89% were female and 28.5% were smokers. Regarding the thyroid function of the population prior to treatment, hyperthyroidism was found in 82%, hypothyroidism in 11% and euthyroidism in 7%; and after treatment, hyperthyroidism was found in 78.6% (subclinical), euthyroidism in 17.9% and hypothyroidism in 3.5%. The majority (92.6%) had positive thyrotropin receptor antibodies, with an average of 18 ± 9.9 mIU/Ml. Regarding the activity of orbitopathy according to the CAS scale, an average of 4.1 ±1.0 was found before treatment and 1.2 ±1.4 after; Of them, 46.4% presented a mild condition according to the severity scale, 39% without severity criteria and 14% persisted in moderate-severe. Improvement in visual acuity was noted after treatment (57.1%), the average exophthalmia before treatment was 22.2 mm and after 21.1 mm; Diplopia occurred in 7.1% before treatment and in 3.6% after treatment. Conclusion: Treatment with intravenous glucocorticoids in moderate-severe Graves' orbitopathy (EUGOGO 2016 scheme) was very effective, reversing the activity and consequently helping to reduce the severity, in the vast majority of our patients. This could be explained because the orbitopathy was incipient and by the high degree of patient adherence in the context of well-protocolized multidisciplinary management.

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)

Low dose oral glucocorticoid therapy in lichen planus: A retrospective cohort study

Background: There are various topical and systemic treatment options for the management of lichen planus. However, it is often difficult to achieve long-term disease control and many of the common therapies may be associated with unwanted side effects. Aims: To evaluate the effectiveness of 8 mg oral methylprednisolone administered daily in lichen planus by the analysis of medical records. Methods: In this retrospective cohort study, we compared the rates of improvement between two groups of patients. The first group received 8 mg oral methylprednisolone daily for at least one month. In the second group, patients with similar parameters to the first group (age, sex, disease manifestation) but without systemic glucocorticoid therapy were included. Fisher’s exact test was used to compare the rates of remission in the two groups. Results: In the daily oral methylprednisolone (n = 24) and no systemic corticosteroids (n = 16) groups, 23 (95.8%) and 6 (37.5%) patients achieved partial or complete remission, respectively. The frequency of improvement was significantly higher in patients who received oral methylprednisolone (P < 0.0001). Limitations: Limitations of this study include its retrospective design and the relatively small sample size. Conclusion: Low dose oral glucocorticoid therapy may be an effective option for the systemic treatment of lichen planus. Based on our results and previous studies, instead of higher doses, longer therapy duration with low doses should be considered.

Paraccocidiomicosis sistémica en consumidor crónico de corticoides

La Paracoccidiomicosis es una infección endémica. Junto con la histoplasmosis, son las infecciones micóticas más frecuentes en Latinoamérica. Esta micosis puede ser de afección local o sistémica, con un marcado trofismo por los pulmones, órganos linfoides, hígado, glándulas suprarrenales, piel y mucosa. Presentamos el caso de un varón adulto, consumidor crónico de corticoides, que desarrolla una paracoccidiomicosis sistémica con afección pulmonar y de glándulas suprarrenales con buena repuesta a la terapéutica antifúngica.

Paracoccidiomycosis is an endemic infection, together with histoplasmosis, they are the most frequent fungal infections in Latin America. This mycosis can be of local or systemic affection, with a marked trophism by the lungs, lymphoid organs, liver, adrenal glands, skin and mucosa. We present the case of an adult male, chronic steroid user, who develops systemic paracoccidiomycosis with pulmonary and adrenal gland involvement with good response to antifungal therapy.

Vasculitis del sistema nervioso central

La vasculitis primaria del Sistema Nervioso Central (VPSNC) se refiere a un grupo de enfermedades que resultan de la inflamación y destrucción de los vasos sanguíneos de la médula espinal, encéfalo y meninges, tanto en el sector venoso como arterial, esto puede conducir a la oclusión o formación de aneurismas, con las consiguientes alteraciones isquémico-hemorrágicas.1 La presentación es heterogénea y poco sistematizable. El diagnóstico se establece con un cuadro clínico compatible, una angiografía o biopsia del parénquima encefálico y/o meninges que evidencien vasculitis. Presentamos el caso de un paciente portador de retrovirus con probable VPSNC con clínica compatible, hallazgos imagenológicos sugestivos, con escasa alteración de LCR y EEG.2

Primary vasculitis of the Central Nervous System (VPSNC) refers to a group of diseases that result from inflammation and destruction of the blood vessels of the spinal cord, brain and meninges, both in the venous and arterial sector, this can lead to the occlusion or formation of aneurysms, with the consequent ischemic-hemorrhagic alterations.1 The presentation is heterogeneous and little systematizable. The diagnosis is established with a compatible clinical picture, an angiography or biopsy of the brain parenchyma and/or meninges that show vasculitis. We present the case of a patient with a retrovirus with probable NCPSV with compatible symptoms, suggestive imaging findings, with little CSF and EEG alteration.2

Brief review of pathophysiological disorders as consequence of psychological stress / Breve revisión de los trastornos fisiopatológicos como consecuencia del estrés psicológico

Background: Psychological stress is a reaction to an unexpected situation that favours adaptation and response to the event. However, when psychological stress is chronic or very intense, it can induce changes in various systems and tissues, causing diseases or aggravating existing ones. Objective: To briefly analyse the pathophysiological conditions caused by psychological stress. Method: A narrative review of the scientific literature on pathophysiological conditions as a consequence of psychological stress was performed. Results: Psychological stress can induce various conditions at the gastrointestinal, immune and cardiovascular levels. This is mainly due to the neurobiological and endocrine response because when faced with a stressful stimulus, a deregulated release of glucocorticoids and catecholamines is generated, altering the normal physiology of the organism. Gastrointestinal disorders are mainly due to goblet cell dysfunction, resulting in intestinal hyperpermeability, inflammation and infection. Changes at the immune level lead to an increase in inflammatory responses but a decrease in the protective activities of the immune system. Finally, cardiovascular conditions include atherosclerosis, increased blood pressure and stroke. Conclusion: Psychological stress can induce real physiological pathologies and, in some cases, fatal ones. Some of the molecular mechanisms involved in these pathologies have already been studied and identified. Knowledge of these molecular mechanisms can help clinicians and therapists to improve the treatment and therapy of patients.

Introducción: El estrés psicológico es una respuesta a una situación inesperada que favorece la adaptación y la respuesta ante dicho evento. Sin embargo, cuando el estrés psicológico es crónico o muy intenso, se pueden desencadenar afecciones en diversos sistemas y tejidos, generando enfermedades o empeorando las ya existentes. Objetivo: Analizar brevemente las afecciones fisiopatológicas causadas por el estrés psicológico. Método: Se realizó una revisión narrativa con la literatura científica sobre las afecciones fisiopatológicas debidas al estrés psicológico. Resultados: El estrés psicológico puede desencadenar diversas afecciones a nivel gastrointestinal, inmunitario y cardiovascular. Esto se debe principalmente a la respuesta neurobiológica y endócrina, ya que ante estímulos estresores, se genera una liberación desregulada de glucocorticoides y catecolaminas que alteran la fisiología normal del organismo. Las afecciones a nivel gastrointestinal se deben principalmente a la disfunción de las células caliciformes, dando como consecuencia hiperpermeabilidad intestinal, inflamación e infecciones. Las alteraciones a nivel inmunitario generan un aumento en las respuestas inflamatorias pero una reducción en las actividades protectoras del sistema inmune. Por último, las afecciones cardiovasculares incluyen ateroesclerosis, aumento de la presión arterial y derrames cerebrales, entre otros. Conclusión: El estrés psicológico puede causar patologías fisiológicas reales y, en algunos casos, mortales. Algunos de los mecanismos moleculares implicados en estas patologías ya han sido estudiados y establecidos. Conocer estos mecanismos moleculares puede ayudar a los médicos y terapeutas a mejorar el tratamiento y la terapia del paciente.

Effects of extrafine-particle versus fine-particle inhaled corticosteroids combined with formoterol on large and small airway function in patients with bronchial asthma / 中国医师进修杂志

Objective:To compare the effects of extrafine-particle versus fine-particle inhaled corticosteroids (ICS) combined with formoterol on clinical symptoms, airway inflammation and airway function in patients with bronchial asthma (referred to as asthma).Methods:This prospective, randomized controlled clinical trial enrolled a total of 111 patients diagnose of asthma and cough variant asthma with forced expired volume in one second (FEV 1) percentage of predicted (FEV 1%pred) >70% in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from November 2020 to October 2022. The patients were divided into observation group (57 cases) and control group (54 cases) by random digits table method. The patients in observation group were treated with extrafine-particle ICS combined with formoterol, while the patients in control group were treated with fine-particle ICS combined with formoterol. Both groups were treated for 4 weeks. During treatment 10 patients lost follow up and a total of 101 patients complete the final study: 52 cases in observation group and 49 cases in control group. At baseline, the asthma control test (ACT) score was calculated to evaluate the clinical symptoms, fractional exhaled nitric oxide (FeNO) was applied to evaluate the airway inflammatory level, and the pulmonary function test and bronchodilation test were perfromed. The symptom relief time was record. After treatment, all of the parameters were reevaluated. Results:The FEV 1, peak expiratory flow (PEF), forced expired flow at 50% of forced vital capacity (MEF 50), forced expired flow at 25% of forced vital capacity (MEF 25), maximal expiratory flow-volume curve (MMEF) and ACT score after treatment in both groups were significantly improved compared to baseline, and there were statistical differences ( P<0.01). The improvement of ACT score in observation group was significantly higher than that in control group: (5.90 ± 2.25) scores vs. (4.10 ± 2.18) scores, and there was statistical difference ( P<0.01); there were no statistical differences in the symptom relief time and the improvement rates of FEV 1, PEF, MEF 50, MEF 25, MMEF between the two groups ( P>0.05). Further subgroup analysis was performed on 78 patients with small airway dysfunction, 39 patients were treated with extrafine-particle ICS combined with formoterol (observation subgroup), and 39 patients were treated with fine-particle ICS combined with formoterol (control subgroup). The improvement of ACT score in observation subgroup was significantly higher than that in control subgroup: (6.05 ± 2.22) scores vs. (3.95 ± 2.19) scores, and there was statistical difference ( P<0.01); there were no statistical differences in the symptom relief time and the improvement rates of FEV 1, PEF, MEF 50, MEF 25, MMEF between the two subgroups ( P>0.05). Spearman correlation analysis result showed that the improvement rates of MEF 50, MEF 25 and MMEF after treatment were positive correlated with baseline bronchodilator responses of FEV 1, FEV 1/FVC, MEF 50, MEF 25, MMEF ( r = 0.22 to 0.58, P<0.05), but not with baseline bronchodilator responses of PEF ( P>0.05). In terms of safety, neither of the two treatments had major adverse reactions that affect treatment. Conclusions:For asthma patients with baseline FEV 1%pred>70%, the extrafine-particle ICS combined with formoterol has more significantly improved of clinical symptoms compared to fine-particle ICS combined with formoterol, and potentially with better safety profile. The improvement ratio of small airway function parameters in baseline bronchodilation test could potentially predict treatment response.

Correlation analysis between renin-angiotensin system and bone mineral density in children with glucocorticoid-induced osteoporosis / 中华内分泌外科杂志

Objective:To investigate the relationship between renin-angiotensin system (RAS) and bone mineral density in children with glucocorticoids-induced osteoporosis (GIOP) .Methods:From Apr. 2020 to May. 2021, 53 children with GIOP were recruited in the Children’s Hospital of Taiyuan Maternal and Child Health Hospital and included in the observation group, and 47 children who received glucocorticoid therapy but did not suffer from GIOP were included in the control group. The levels of serum RAS components and bone mineral density of the two groups of pediatric patients were detected and compared, and the risk clinical indicators affecting bone mineral density and GIOP were analyzed.Results:There were no significant differences between the observation group and the control group in terms of gender, age, BMI, disease type, type of glucocorticoid use, use of anti-osteoporosis (OP) drugs, expression levels of Angiotensin converting enzyme 2 (ACE2) or angiotensin II (Ang Ⅱ) (all P>0.05) . The bone density value of the observation group was lower than those of the control group, and the levels of angiotensin converting enzyme (ACE) (1.19±0.23) , angiotensin receptor 1 (AT1R) (1.24±0.24) , angiotensin receptor 2 (AT2R) (1.14±0.17) , and Mas receptor (MasR) (1.11±0.28) were significantly higher than those of the control group (1.00±0.23, 1.00±0.25, 1.00±0.21, 1.00±0.20) , and the differences were statistically significant (all P<0.05) . Pearson analysis showed that bone mineral density was negatively correlated with the levels of ACE ( r=-0.34, P=0.013) , AT1R ( r=-0.41, P=0.002) and AT2R ( r=-0.34, P=0.014) , and stepwise regression model showed that ACE ( t=-2.21, P=0.032) and AT1R ( t=-2.92, P=0.005) were the main factors affecting bone mineral density. Logistic regression model analysis showed that bone mineral density ( OR=0.85, P<0.001) , Ang Ⅱ ( OR=0.53, P=0.041) and AT2R ( OR=2.00, P=0.024) were independent clinical risk factors affecting GIOP (all P<0.05) . Conclusion:RAS components ACE and AT1R are independent risk factors affecting bone mineral density in children with GIOP, and are significantly correlated with bone mineral density in children.

Mechanism of action of glucocorticoid receptors in the growth of hepatoma cells / 国际肿瘤学杂志

The glucocorticoid receptor (GR) plays a critical role in signal transduction, expression of related genes and apoptosis of cancer cells. Hepatocellular carcinoma is characterized by high aggressiveness and mortality. In the exploration of the relationship between GR and hepatocellular carcinoma, numerous studies have shown that GR has an inhibitory effect on the growth of hepatocellular carcinoma cells, which provides new ideas and methods for the clinical application of GR in the treatment of hepatocellular carcinoma.

Efficacy of glucocorticoid stent implantation in ethmoid sinus after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To evaluate the efficacy of glucocorticoid sinus stents implanted 2 weeks after functional endoscopic sinus surgery（FESS） for the treatment of chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:CRSwNP patients with similar bilateral lesions were randomly divided into two groups, with a stent group of 25 patients and a control group of 24 patients. Patients in the stent group had glucocorticoid sinus stents implanted into the bilateral ethmoid sinuses 2 weeks after FESS, while the control group underwent postoperative debridement only. Follow-up assessments occurred at postoperative weeks 2, 4, 8, and 12. Patients were asked to assess their sensation of nasal symptoms using a 10-point visual analog scale. Efficacy was assessed by endoscopic evaluations. Sinus obstruction, crusting/coagulation, polyp formation, middle turbinate position, adhesions, mucosa epithelialization, and postoperative intervention were assessed as efficacy outcomes. GraphPad Prism 9 was applied for statistical analysis. Results:At 4 and 8 weeks postoperatively, the stent group showed significant improvement in VAS scores of nasal congestion and runny nose compared with the control group（P<0.05）. No significant difference was observed in the VAS scores of head and facial stuffiness, loss of smell, or nasal dryness/crusting between the two groups（P>0.05）. Compared with the control group, the stent group had a lower rate of polypoid formation at 4, 8, and 12 weeks postoperatively. At postoperative week 12, the rate of mucosal epithelialization in the ethmoid cavity was significantly higher in the stent group. During the follow-up, the frequency of postoperative intervention was significantly lower in the stent group than in the control group（P<0.05）. Besides, a lower incidence of middle turbinate lateralization was found in the stent group at 8 and 12 weeks postoperatively. At 8 weeks postoperatively, the stent group had a percentage of adhesion lower than that of the control group（all P<0.05）. Conclusion:Implantation of glucocorticoid sinus stents after FESS can maintain sinus cavity patency, improve the inflammatory status of the operative cavity, reduce postoperative interventions, and promote benign regression of the operative cavity.

Fisiopatología de la programación fetal y su repercusión en la salud futura / Pathophysiology of fetal programming and its impact on the future health

Resumen ANTECEDENTES: Durante la vida intrauterina, las alteraciones en el microambiente fetal causadas por desequilibrios nutricionales y metabólicos de la madre pueden dejar huellas epigenéticas y efectos persistentes en la vida adulta de su hijo que habrán de predisponerlo a enfermedades crónicas futuras. OBJETIVO: Llevar a cabo una revisión sistemática de la fisiopatología de la programación fetal y su repercusión en la salud futura del feto. METODOLOGÍA: Búsqueda en la base de datos de PubMed de artículos publicados, en los últimos 10 años, en inglés o español, con los MeSH "fetal programming"; "pathophysiology", con su correspondiente traducción. Se incluyeron artículos originales y de revisión con criterios PRISMA para revisiones sistemáticas. RESULTADOS: Se encontraron 38 artículos, y se agregaron 7 de información complementaria y sustento para la discusión. En su análisis queda clara la relación entre las condiciones fisiopatológicas reportadas de desnutrición, sub y sobrealimentación, diabetes mellitus gestacional, obesidad, resistencia a la insulina, glucocorticoides y preeclampsia con enfermedades de la infancia, adolescencia y adultez. Se encontró evidencia de disruptores endocrinos, melatonina y disbiosis con enfermedades de la infancia y vida adulta. Así mismo, la interrupción de la angiogénesis durante el desarrollo pulmonar que conduce a hipertensión arterial pulmonar y enfisema, todo ello originado por la programación fetal epigenética. Se encontraron diferencias en el patrón de metilación de placentas prematuras en comparación con las de término. CONCLUSIONES: Las anormalidades que sobrevienen durante el embarazo modifican la programación fetal y dan pie a las enfermedades que aparecerán durante la infancia, adolescencia y adultez, como consecuencia de los cambios en el patrón de metilación de los genes.

Abstract BACKGROUND: During intrauterine life, alterations in the fetal microenvironment caused by maternal nutritional and metabolic imbalances may leave epigenetic imprints and persistent effects on fetal adult life that will predispose the fetus to future chronic diseases. OBJECTIVE: To carry out a systematic review of the pathophysiology of fetal programming and its impact on the future health of the fetus. METHODOLOGY: Search in the PubMed database of articles published in the last 10 years, in English or Spanish, with the MeSH "fetal programming"; "pathophysiology", with their corresponding translation. Original and review articles with PRISMA criteria for systematic reviews were included. RESULTS: Thirty-eight articles were found, and seven were added for complementary information and support for discussion. In their analysis the relationship between the reported pathophysiological conditions of under-, under- and over-nutrition, gestational diabetes mellitus, obesity, insulin resistance, glucocorticoids and pre-eclampsia with diseases of childhood, adolescence and adulthood is clear. Evidence of endocrine disruptors, melatonin and dysbiosis was found with diseases of childhood and adulthood. Also, disruption of angiogenesis during lung development leads to pulmonary arterial hypertension and emphysema, all caused by epigenetic fetal programming. Differences were found in the methylation pattern of preterm placentas compared to term placentas. CONCLUSIONS: Abnormalities that occur during pregnancy modify fetal programming and give rise to the diseases that will appear during childhood, adolescence, and adulthood, because of changes in the methylation pattern of genes.

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.

Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study)

Abstract Introduction Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. Objective The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. Methods The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). Results There was a strong positive correlation between fructosamine and HbA1c (n = 318, r= 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r= 0.61, p < 0.001) or using glucocorticoids (n = 96, r= 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r= 0.66, p < 0.001), hypoproteinemia (n = 54, r= 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r= 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r= 0.54, p = 0.001) and with reduced eGFR (n = 67, r= 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r= 0.49, p < 0.001; n = 111, r= 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. Conclusions Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

Preliminary study on the process and prognosis of 55 cases of esophageal stricture after circumferential endoscopic submucosal dissection / 中华消化杂志

Objective:To investigate the characteristics, process, and prognosis of esophageal stricture after circumferential endoscopic submucosal dissection (ESD), and to preliminarily analyze the prevention and treatment effects of simple dilation, stent placement, mucosal transplantation, and glucocorticoid (hereinafter referred to as hormone) application in esophageal stricture.Methods:From August 2017 to March 2022, at the First Affiliated Hospital of Zhengzhou University, the clinical and follow-up data of 55 patients who underwent circumferential ESD for early esophageal cancer and precancerous lesions were retrospectively analyzed. According to the prevention and treatment methods for esophageal stricture, the patients were divided into two groups: simple dilation group (23 cases) and combined dilation group (32 cases). The combined dilation group was divided into mucosal transplantation subgroup (9 cases), stent placement subgroup (14 cases), hormone application subgroup (7 cases), and bleomycin subgroup (2 cases, excluded from comparative analysis due to limited cases). Overall prognosis of patients was observed. Treatment efficacy, prognosis, and adverse events were compared among the simple dilation group, mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup. Independent samples t-test, chi-square test, and Fisher′s exact test were used for statistical analysis. Results:Among the 55 patients, the follow-up time was (894.1±417.7) days. Refractory esophageal stricture (total dilation times ≥ 5) occurred in 33 patients (60.0%). Fifty-two patients (94.5%) achieved clinical remission of the stricture. The total number of dilations was 5.8±4.0, and the average dysphagia-free period was (52.3±37.1) days. The dysphagia-free period of mucosal transplantation subgroup was longer than that of the simple dilation group, stent placement subgroup, and hormone application subgroup ((114.5±50.0) days vs. (40.9±20.0), (39.7±10.0), and (40.9±25.5) days, respectively), and the differences were statistically significant ( t=4.82, 3.77 and 3.14, P<0.001, =0.011, =0.009). There were no statistically significant differences between the simple dilation group and the mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup in the total number of dilations (6.8±4.8 vs. 3.0±2.5, 5.8±2.2, and 5.7±5.0), stricture remission rate (95.7%, 22/23 vs. 8/9, 13/14, and 7/7), and incidence of adverse events (17.4%, 4/23 vs. 5/9, 5/14, and 2/7; all P>0.05). Conclusions:Esophageal stricture formed after circumferential ESD shows the characteristics of recurrence and intractability. The over all number of dilations is high, and the average dysphagia-free period is short. Most patients can achieve clinical remission of the stricture after multiple times of endoscopic dilation treatment. However mucosal transplantation, stent placement, and hormone application cannot well intervene the natural process of esophageal stricture.

Surveys on management of neonatal respiratory distress syndrome in ten hospitals in Northwest China in 2016 and 2021 / 中华围产医学杂志

Objective:To analyze the status of neonatal respiratory distress syndrome (RDS) management in 10 hospitals in Northwest China over the past five years and to investigate the strategies for improving the prevention and treatment of RDS.Methods:This retrospective study involved premature infants with RDS who were admitted to the neonatal intensive care units (NICU) of 10 hospitals (six in Shaanxi Province, three in Gansu Province, and one in Xinjiang Uygur Autonomous Region) of the Northwest China Neonatal Collaborative Group within 3 d after birth from January 1 to December 31, 2016, and from January 1 to December 31, 2021. Basic information, perinatal condition, treatment approaches, complications, and prognosis of the patients were compared. T-test, rank sum, and Chi-square tests were used for statistical analysis. Result:(1) This study enrolled 322 premature infants with RDS in 2016 and 349 in 2021. Premature infants at the gestational age of 30 to 33 weeks were mainly affected, and the majority were male [64.3% (207/322) and 57.3% (200/349)]. The average maternal age in 2021 was older than that in 2016 [(30.6±4.8) years vs (28.6±5.4) years, t=24.02, P<0.001], and the proportion of women at advanced maternal age was also higher in 2021 [19.2% (67/349) vs 12.4% (40/322), χ2=4.18, P<0.05]. (2) The proportions of pregnancies conceived with assisted reproductive technologies [11.7% (41/349) vs 1.9% (6/322), χ2=25.12], underwent routine prenatal examinations [58.5% (204/349) vs 30.4% (98/322), χ2=53.33], exposed to steroids [62.2% (217/349) vs 28.6% (92/322), χ2=82.58] and delivered by cesarean section or elective cesarean section [73.6% (257/349) vs 51.6% (166/322), χ2=35.06; 24.1% (84/349) vs 6.5% (21/322), χ2=39.07], as well as the ratio of cesarean scar pregnancy [7.4% (26/349) vs 3.4% (11/322), χ2=5.23] were all higher in 2021 than those in 2016 (all P<0.05). Moreover, the incidence of fetal distress [30.1% (105/349) vs 20.2% (65/322), χ2=8.68], gestational hypertension [24.6% (86/349) vs 13.0% (42/322), χ2=14.59], premature rupture of membranes [16.0% (56/349) vs 10.2% (33/322), χ2=4.89], meconium-stained amniotic fluid [12.6% (44/349) vs 5.6% (18/322), χ2=9.83], placental abruption [10.3% (36/349) vs 5.3% (17/322), χ2=5.84], gestational diabetes mellitus [10.3% (36/349) vs 1.6%(5/322), χ2=22.41], chorioamnionitis [4.6%(16/349) vs 0.9% (3/322), χ2=8.12], thyroid dysfunction [4.3% (15/349) vs 0.6% (2/322), χ2=7.88] and heart disease [4.3% (15/349) vs 0.3% (1/322), χ2=9.17] were higher in 2021 than in 2016 (all P<0.05). (3) In 2021, the rate of pulmonary surfactant (PS) usage, the dosage of porcine PS, and the proportion of bovine PS usage were all significantly higher than those in 2016 [73.6% (257/349) vs 67.1% (216/322), χ2=11.62; (178.5±38.0) mg/kg vs (165.2±42.8) mg/kg, t=7.85; 47.9% (123/257) vs 19.4% (42/216), χ2=41.72; all P<0.01]. No significant difference in the incidence of intubation-surfactant-extubation (INSURE), early PS administration (≤2 h after birth), or the arterial blood gas values before and after PS treatment was found between the cases enrolled in 2021 and 2016. The duration of antibiotic treatment [7.0 d (5.0-14.0 d) vs 5.0 d (1.0-8.0 d), Z=7.55] and assisted ventilation [144 h (81-264 h) vs 73 h (47-134 h), Z=8.20] and the median hospital stay [24 d(14-42 d) vs 16 d (10-25 d), Z=6.74] were significantly longer in 2021 than in 2016 (all P<0.01). More patients required nasal intermittent positive pressure ventilation [29.6% (100/338) vs 1.0% (3/306), χ2=97.81] and conventional ventilation [42.6% (144/338) vs 30.1% (92/306), χ2=10.87] in 2021 as compared with those five years ago (both P<0.01). (4) In 2021, the incidence of patent ductus arteriosus [15.5% (54/349) vs 6.2% (20/322), χ2=63.40], bronchopulmonary dysplasia [9.2% (32/349) vs 2.8% (9/322), χ2=12.88], persistent pulmonary hypertension [5.4% (19/349) vs 0.6% (2/322), χ2=12.85], periventricular leukomalacia [4.3% (15/349) vs 1.2% (4/322), χ2=7.52] and pneumothorax [3.4% (12/349) vs 0.3% (1/322), χ2=9.68] increased as compared with those in 2016 (all P<0.05), while the incidence of nosocomial infection decreased significantly [7.4% (26/349) vs 19.6% (63/322), χ2=21.37, P<0.001]. (5) The cure rate of premature infants with RDS was 70.8% (247/349) in 2021, which was significantly higher than that in 2016 [56.2% (181/322), χ2=15.37, P<0.001]. Moreover, the rate of withdrawing treatment and the total mortality rate was lower in 2021 than in 2016 [7.7% (27/349) vs 14.3% (46/322), χ2=7.41; in-hospital: 1.4% (5/349) vs 5.6% (18/322), χ2=8.74; out of hospital: 8.3% (29/349) vs 13.7% (44/322), χ2=4.96; all P<0.05]. Conclusions:The clinical management of RDS in premature infants in the involved hospitals has been improved. However, there is room for improvement in prenatal examinations.

Effects of antenatal dexamethasone and postnatal pulmonary surfactant combined with respiratory support on lung fluid clearance in preterm rabbits / 中华围产医学杂志

Objective:To explore the effects of prenatal dexamethasone (DEX), postnatal pulmonary surfactant (PS) and respiratory support on the lung fluid clearance in premature rabbits at gestational age (GA) of 25-28 d (full term: 31 d) and their relationship with dynamic compliance of respiratory system (Cdyn), pulmonary morphology and other parameters.Methods:In our previous publications, premature rabbits were divided into four groups according to the intervention strategy: control group, PS-only group, DEX-only group and DEX+PS group in which data of several parameters including wet-to-dry lung weight ratio (W/D), Cdyn and volume density of alveoli (Vv) were retrieved and the lung tissue sections were scanned to recalculate the ratio of perivascular sheath to vascular sectional area (S/V) and lung injury scores-edema (LIS-E). W/D, LIS-E, S/V and Vv were adjusted for birth weight (BW) (divided by BW, represented as W/D/BW, LIS-E/BW, S/V/BW and Vv/BW) and mean Cdyn (Cdyn-m) was adopted. Based on the grouping of previous studies, the intervention groups in this study were divided as DEX group and non-DEX group, and PS group and non-PS group to analyze the influence of DEX and PS on the above parameters. Two independent samples t-test, one-way analysis of variance, LSD test, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis were used for statistical analysis. Results:A total of 196 newborn rabbits receiving mechanical ventilation after birth were included in this study. (1) Effects of DEX: compared with the non-DEX group, the DEX group showed increased W/D/BW (489±69 vs 421±113, t=－2.09), LIS-E/BW (188±57 vs 138±55, t=－2.61) and Vv/BW (20.1±4.9 vs 14.2±4.7, t=－3.60), but decreased S/V (0.33±0.23 vs 0.51±0.25, t=2.23) and S/V/W/D (0.05±0.03 vs 0.07±0.04, t=2.22) at 25 d of gestation; at 26 d of gestation, W/D/BW (472±76 vs 303±44, t=－8.75), LIS-E/BW (189±63 vs 106±36, t=－5.23), Cdyn-m [(0.16±0.07) vs (0.05±0.03) ml/(kg?cmH 2O), 1 cmH 2O=0.098 kPa; t=－7.29] and Vv/BW increased (22.4±5.0 vs 12.2±3.8, t=－7.46), while S/V (0.23±0.19 vs 0.62±0.38, t=4.10), S/V/BW (15.7±12.4 vs 25.7±17.3, t=2.20), S/V/W/D (0.03±0.03 vs 0.08±0.05, t=3.92) and propensity scores decreased [(12.5±1.2) vs (15.1±1.2) scores, t=7.00]; at 27 d of gestation, Cdyn-m increased [(0.23±0.12) vs (0.16±0.07) ml/(kg?cmH 2O), t=－2.43], but S/V (0.32±0.23 vs 0.57±0.39, t=2.57) and S/V/W/D decreased (0.05±0.04 vs 0.09±0.06, t=2.55); at 28 d of gestation, W/D/BW (270±64 vs 162±33, t=－8.09), LIS-E/BW (72±32 vs 35±20, t=－5.17), S/V (0.90±0.60 vs 0.59±0.48, t=－2.81), S/V/BW (34.0±23.6 vs 15.2±12.7, t=－3.77) and Vv/BW increased (16.9±4.3 vs 9.2±2.9, t=－8.04); the differences were all statistically significant (all P<0.05). (2) Effects of PS: compared with the non-PS group, the PS group had decreased LIS-E/BW at 25, 26 and 27 d of gestation, increased Cdyn-m and Vv/BW at 25 and 27 d of gestation and higher propensity scores at 25 d of gestation (all P<0.05). (3) The correlation between gestational age and each index: gestational age was positively correlated with S/V ( r=0.31, P<0.05), but negatively correlated with W/D/BW and LIS-E/BW ( r=－0.73 and－0.63, both P<0.05). Conclusions:The pharmacological action of prenatal DEX on lung fluid clearance is mainly confined to preterm rabbits at the GA of 28 d which is supported by mechanical ventilation. Prenatal treatment with DEX and/or postnatal PS can improve the early respiratory function in preterm rabbits between GA of 25-27 d, but had no substantial impact on lung fluid clearance. The GA-related lung maturation appears to play a crucial role, in comparison with medications, in lung fluid clearance.

A case of survived extremely preterm infant with severe bronchopulmonary dysplasia after comprehensive therapy / 中华围产医学杂志

This article reported the comprehensive management of an extremely preterm infant with severe bronchopulmonary dysplasia. The patient born at 26 +6 gestational weeks was transferred to Children's Hospital of Fudan University due to invasive mechanical ventilation dependence at 61 d after birth and was diagnosed with severe bronchopulmonary dysplasia. A comprehensive treatment plan was adopted, including appropriate fluid restriction, improving nutrition, glucocorticoid administration, using antibiotics against Ureaplasma urealyticum infection to reduce pulmonary parenchymal lesions and alleviating pulmonary hypertension. The preterm infant was successfully extubated to non-invasive ventilation and subsequently weaned to a high-flow nasal cannula. Then, the patient was discharged at 372 d after birth (correct gestational age nine months and six days). At the 3-month follow-up after discharge, the patient remained on high-flow oxygen, but with lower flow and concentration of oxygen. Moreover, the growth, development and lung images were significantly improved. Follow-up to correct gestational age one year and 11 months, the child was not on oxygen any more, but on rehabilitation due to language and motor development retardation.