The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Abstract Objective: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. Methods: Between July 2018- February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. Results: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p<0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p>0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p< 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p>0.05). Conclusion: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. Level of evidence: 1B.

Proteinuria y síndrome nefrótico / Proteinuria and Nephrotic Syndrome

Introducción: El síndrome nefrótico es una patología que afecta el complejo glomerular del riñón, se caracteriza por una proteinuria mayor 3500 mg/d. De acuerdo a la respuesta de los esteroides se puede clasificar en síndrome nefrótico en esteroide resistente o esteroide sensible. Objetivo: Determinar la relación que existe entre la proteinuria y las variantes del síndrome nefrótico en adultos. Métodos: Se realizó un estudio descriptivo, retrospectivo, tipo serie de casos, con una población de 28 pacientes. Se recolectaron y se procesaron los datos a través del software Epi-Info 7,2TM; la frecuencia simple, la media estadística, prueba t de Student, y el coeficiente de correlación de Pearson. Resultados: En el análisis combinatorio de los fármacos adyuvantes para síndrome nefrótico, el grupo que utilizó antiproteinúricos pero no estatinas, demostró una diferencia estadísticamente significativa entre la proteinuria postratamiento media del grupo de síndrome nefrótico esteroideo resistente (6202 mg/d) vs síndrome nefrótico esteroideo sensible (65,9 mg/d) (valor de p 0,418). Existe una correlación negativa entre los niveles proteinuria postratamiento y el nivel de albúmina sérica postratamiento (r = - 0,7 valor de p < 0,00001). Conclusiones: Se demostró la ausencia de asociación entre la proteinuria inicial y las variantes de síndrome nefrótico esteroide sensible y esteroide resistente (valor de p = 0,8)(AU)

Introduction: Nephrotic syndrome is a pathology that affects the glomerular complex of the kidney, characterized by proteinuria greater than 3500 mg/d. According to the response to steroids, nephrotic syndrome can be classified as steroid-resistant or steroid-sensitive. Objective: To determine the relationship between proteinuria and the variants of the nephrotic syndrome in adults. Methods: A descriptive, retrospective, case series type study was carried out with a population of 28 patients. The data was collected and processed through Epi-Info 7.2TM software; simple frequency, statistical mean, student's t-test, and Pearson's correlation coefficient. Results: The statistically significant difference was obtained in the antiproteinuric and non-statin group, between the mean post-treatment proteinuria of the steroid resistant nephrotic syndrome group (6202 mg/d) in comparison to steroid sensitive nephrotic syndrome (65.9 mg/d) (p value 0.0418). There is negative correlation between post-treatment proteinuria levels and post-treatment serum albumin level (r= -0.7 p value <0.00001). Conclusions: The absence of association between initial proteinuria and steroid-sensitive and steroid-resistant variants of nephrotic syndrome was demonstrated (p value=0.8)(AU)

Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation / 中华血液学杂志

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Factors predictive of treatment response and survival in Filipino patients with autoimmune hepatitis

Background@#There is a dearth of data on Filipino patients with autoimmune hepatitis (AIH). We aimed to describe the demographic and clinical profiles of patients with AIH and to characterize clinical outcomes and treatment responses.@*Methods@#A retrospective cohort study involving patients from two tertiary centers diagnosed with AIH from January 1, 2007, to December 31, 2019, was included. Disease remission was defined as the normalization of ALT levels, while failure was defined as an increase in ALT levels over baseline or clinical deterioration.@*Results@#A total of 48 patients were identified between 2007 to 2019. The median age at presentation was 51 (27-79 yrs.). Liver cirrhosis was already present in 37.5% (27.1% decompensated) on diagnosis. Aside from a higher histologic activity index in females (p=0.047), there were no gender-specific differences. Disease remission was achieved in 41.9% of patients at 6 months, while only 9.3% failed. At the final disposition, remission rates had slightly increased to 58%, but failure rates had risen to 12%. Treatment responses at both 6 and 12 months and MELD and Child-Pugh class influenced treatment responses at final disposition. Median overall survival was 102 weeks and was influenced by the presence of liver dysfunction and 12 months and final treatment responses.@*Conclusion@#Autoimmune hepatitis remains an important cause of morbidity and mortality. The results of the study highlight the need for immunosuppressive therapy to induce early remission for a higher likelihood of subsequent biochemical remission to reduce the risk of liver-related mortality.

Clinical features and prognosis of 118 children with histiocytic necrotizing lymphadenitis / 中华儿科杂志

Objective: To explore the clinical features and prognosis of children with histiocytic necrotizing lymphadenitis (HNL). Methods: The clinical data of 118 children with HNL diagnosed and treated in the Department of Rheumatology and Immunology of Children's Hospital, Capital Institute of Pediatrics from January 2014 to December 2021 were retrospectively analyzed. The clinical symptoms, laboratory examination, imaging examination, pathological findings, treatment and follow-up were analyzed. Results: Among the 118 patients, 69 were males and 49 were females. The age of onset was 10.0 (8.0, 12.0) years, ranging from 1.5 to 16.0 years. All the children had fever lymph node enlargement, blood system involvement in 74 cases (62.7%), skin injury in 39 cases (33.1%). The main manifestations of laboratory examination were increased erythrocyte sedimentation rate in 90 cases (76.3%), decreased hemoglobin in 58 cases (49.2%), decreased white blood cells in 54 cases (45.8%) and positive antinuclear antibody in 35 cases (29.7%). Ninety-seven cases (82.2%) underwent B-mode ultrasound of lymph nodes, showing nodular lesions with low echo in the neck; 22 cases (18.6%) underwent cervical X-ray and (or) CT; 7 cases (5.9%) underwent cervical magnetic resonance imaging. Lymph node biopsy was performed in all 118 cases, and the pathological results did not support malignant diseases such as lymphoma or Epstein-Barr virus infection, suggesting HNL. Fifty-seven cases (48.3%) recovered without treatment, 61 cases (51.7%) received oral steroid therapy, and 4 cases (3.4%) received indomethacin as anal stopper. The 118 cases were followed up for 4 (2, 6) years, ranging from 1 to 7 years, 87 cases (73.7%) had one onset and did not develop into other rheumatological diseases, and 24 cases (20.3%) had different degrees of recurrence, 7 cases (5.9%) had multiple system injuries, and all of the tested autoantibodies were positive for medium and high titers. All of them developed into other rheumatic immune diseases, among which 5 cases developed into systemic lupus erythematosus and 2 cases developed into Sjogren's syndrome; 7 cases were given oral steroid therapy, including 6 cases plus immunosuppressant and 2 cases receiving methylprednisolone 20 mg/kg shock therapy. Conclusions: The first-onset HNL portion is self-healing, hormone-sensitive and has a good prognosis. For HNL with repeated disease and multiple system injury, antinuclear antibody titer should be monitored during follow-up, and attention should be paid to the possibility of developing into other rheumatological diseases, with poor prognosis.

Meta-analysis of the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates / 中华儿科杂志

Objective: To systematically evaluate the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates. Methods: Eight databases in either Chinese or English, including PubMed, the Cochrane Library, Embase, Medline, Scopus, CNKI, Wanfang and VIP, were searched to extract the studies on the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates published from the establishment of each database to December 2022. The Meta-analysis was performed using Stata 14.0 statistical software. Results: A total of 9 studies were included in this Meta-analysis, including 6 retrospective cohort studies, 2 prospective cohort studies and 1 randomized controlled trial (RCT) study, involving 9 143 premature infants. The Meta-analysis showed that prenatal steroid exposure increased the risk of late preterm neonatal hypoglycemia (RR=1.55, 95%CI 1.25-1.91, P<0.001). The similar correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates was all found in the following subgroups: North America (RR=1.57, 95%CI 1.37-1.80, P<0.001), enrolling pregnant women with gestational diabetes (RR=1.62, 95%CI 1.26-2.08, P<0.001), A-grade literature quality (RR=1.43, 95%CI 1.14-1.79, P=0.002), criteria for hypoglycemia ≤40 mg/dl (1 mg/dl=0.056 mmol/L, RR=1.49, 95%CI 1.28-1.73, P<0.001), sample size of 501-1 500 (RR=1.69, 95%CI 1.19-2.40, P=0.003) and >1 500 (RR=1.65, 95%CI 1.48-1.83, P<0.001), steroid injection dosage and frequency of 12 mg 2 times (RR=1.66, 95%CI 1.50-1.84, P<0.001), the time interval from antenatal corticosteroid administration to delivery of 24-47 h (RR=1.98, 95%CI 1.26-3.10, P=0.003), unadjusted gestational age (RR=1.78, 95%CI 1.02-3.10,P=0.043) and unadjusted birth weight (RR=1.80, 95%CI 1.22-2.66, P=0.003). Meta-regression results showed that steroid injection frequency and dose were the main sources of high heterogeneity among studies (P=0.030). Conclusion: Prenatal steroid exposure may be a risk factor for hypoglycemia in late preterm neonates.

Establishment and validation of clinical prediction model for steroid-resistant nephrotic syndrome in children / 中华儿科杂志

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ2=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ2=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.

Biosynthesis of steroidal intermediates using Mycobacteria: a review / 生物工程学报

Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared through Mycobacteria transformation, and then modified chemically or enzymatically into advanced steroidal compounds. Compared with the "diosgenin-dienolone" route, Mycobacteria transformation has the advantages of abundant raw materials, cost-effective, short reaction route, high yield and environmental friendliness. Based on genomics and metabolomics, the key enzymes in the phytosterol degradation pathway of Mycobacteria and their catalytic mechanisms are further revealed, which makes it possible for Mycobacteria to be used as chassis cells. This review summarizes the progress in the discovery of steroid-converting enzymes from different species, the modification of Mycobacteria genes and the overexpression of heterologous genes, and the optimization and modification of Mycobacteria as chassis cells.

Difference in liver injury induced by dictamnine between males and females: based on untargeted metabolomics / 中国中药杂志

In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered "non-toxic" TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P<0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

Antiproliferative effects of 13α/ß-steroids on triple-negative MDA-MB-231 breast cancer cells: unraveling intracellular signaling without ERα

Abstract This study aimed to investigate the activities of novel 20(R)-3,20-dihydroxy-19-norpregn-1,3,5(10)-trienes (kuz7 and kuz8b) of natural 13ß- and epimeric 13α-series against triple-negative MDA-MB-231 breast cancer cells. High antiproliferative activity of synthesized compounds kuz8b and kuz7 against MDA-MB-231 triple-negative cancer cells was revealed. The steroid kuz7 of natural 13ß-configuration was more active against MDA-MB-231 cells than the 13α-steroid kuz8b. Cell cycle analysis revealed common patterns for the action of both tested compounds. The number of cells in the subG1 phase increased in a dose-dependent manner, indicating induction of apoptosis, which was also verified by PARP cleavage. In contrast, the number of cells in the G0/G1 phase decreases with increasing compound concentration. Steroid kuz7 at micromolar concentrations reduced the expression of GLUT1, a glucose transporter. High efficacy of the combination of kuz7 with biguanide metformin was shown, and synergistic effects on MDA-MB-231 cell growth and expression of the anti-apoptotic protein Bcl-2 were revealed. According to the obtained results, including the high activity of kuz7 against triple-negative cancer cells, the detected induction of apoptosis, and the decrease in GLUT1 expression, 13ß-steroid kuz7 is of interest for further preclinical studies both alone and in combination with the metabolic drug metformin

Arteritis de células gigantes: ¿Cómo debutan pacientes chilenos? Análisis de casos y revisión de la literatura / Giant cell arteritis. Experience in 32 patients

BACKGROUND: Giant cell Arteritis (GCA) is the most common systemic vasculitis in patients over 50 years. Diagnosis is based on clinical, laboratory, imaging and biopsy. Temporal artery biopsy (TAB) may be inconclusive in up to 40% of patients. AIM: To describe disease features of patients diagnosed with GCA. MATERIAL AND METHODS: Review of pathology reports of giant cell arteritis and clinical records of patients seen with the diagnosis between 2000 and 2019. Demographic, clinical, laboratory, histopathology, imaging, treatment and follow-up variables were analyzed. RESULTS: We fetched 32 patients with a median age at diagnosis of 70.5 years (range 57-90), 81% women. Twenty eight percent had polymyalgia. 72% had only cranial symptoms, 12% had extracranial involvement and 13% exclusive extracranial involvement. The median time from onset of symptoms to diagnosis was two months (range 0.5-8). All had elevated erythrocyte sedimentation rate and c reactive protein. A TAB was performed in 27 patients and in 17 (65.4%) it confirmed the diagnosis. Transmural inflam- mation was the most frequent finding. All patients received steroids. Follow-up information was available from 25 patients and 92% received a steroid-spa- ring agent, usually methotrexate (74%). Ninety two percent achieved clinical remission in the first year and 59% had minor relapses during steroid tapering. CONCLUSIONS: Our patients showed frequent extracranial involvement and TAB was a useful diagnostic tool.

Role of systemic corticosteroids in orbital cellulitis: a meta-analysis and literature review / Papel dos corticosteroides sistêmicos na celulite orbitária: uma metanálise e revisão da literatura ,

Abstract Introduction: The standard management of orbital cellulitis is to administer a combination of intravenous broad-spectrum antibiotics along with treatment of associated sinusitis. Objective: The purpose of this study was to evaluate whether the addition of corticosteroids could lead to earlier resolution of inflammation and improve disease outcome. Methods: We independently searched five databases (PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database) for studies published as recent as December 2019. Of the included studies, we reviewed orbital cellulitis and disease morbidity through lengths of hospitalization, incidence of surgical drainage, periorbital edema, vision, levels or C-reactive protein, and serum WBC levels in order to focus on comparing steroid with antibiotics treated group and only antibiotics treated group. Results: Lengths of hospitalization after admission as diagnosed as orbital cellulitis (SMD = −4.02 [−7.93; −0.12], p -value = 0.04, I2 = 96.9%) decrease in steroid with antibiotics treated group compared to antibiotics only treated group. Incidence of surgical drainage (OR = 0.78 [0.27; 2.23], p -value = 0.64,I2 = 0.0%) was lower in the steroid with antibiotics treated group compared to the antibiotics only treated group. Conclusion: Use of systemic steroids as an adjunct to systemic antibiotic therapy for orbital cellulitis may decrease orbital inflammation with a low risk of exacerbating infection. Based on our analysis, we concluded that early use of steroids for a short period can help shorten hospitalization days and prevent inflammation progression.

Resumo Introdução: O tratamento padrão da celulite orbitária inicia-se com uma combinação de antibióticos intravenosos de amplo espectro concomitante ao tratamento do seio comprometido. Objetivos: O objetivo deste estudo foi avaliar se a adição de corticosteroides poderia levar a uma resolução mais precoce da inflamação e melhorar o desfecho da doença. Método: Fizemos uma pesquisa independente em cinco bancos de dados (PubMed, SCOPUS, Embase, Web of Science e o banco de dados Cochrane) em busca de estudos publicados até dezembro de 2019. Dos estudos incluídos, revisamos a celulite orbitária e a morbidade da doença através dos períodos de internação, incidência de drenagem cirúrgica, edema periorbital, visão, níveis de proteína C-reativa e níveis séricos de leucócitos com foco na comparação do grupo tratado com esteroides e antibióticos e do grupo tratado apenas com antibióticos. Resultados: Os tempos de internação após a admissão dos diagnosticados com celulite orbitária (SMD = -4,02 [-7,93; -0,12], p-valor = 0,04, I2 = 96,9%) diminuíram no grupo tratado com esteroides e antibióticos em comparação ao grupo tratado apenas com antibióticos. A incidência de drenagem cirúrgica (OR = 0,78 [0,27; 2,23], p-valor = 0,64, I2 =0,0%) foi menor no grupo tratado com esteroides e antibióticos em comparação com o grupo tratado apenas com antibióticos. Conclusão: O uso de esteroides sistêmicos como adjuvante da antibioticoterapia sistêmica para celulite orbitária pode diminuir a inflamação orbitária com baixo risco de agravar a infecção. Com base em nossa análise, concluímos que o uso precoce de esteroides por um curto período pode ajudar a encurtar os dias de internação e prevenir a progressão da inflamação.

Classic and current concepts in adrenal steroidogenesis: a reappraisal

ABSTRACT Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a "mineralocorticoid (MC) pathway of zona fasciculata (ZF)", where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11β-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme - CYP11B1/CYP11B2 -, responsible for aldosterone formation in ZF under ACTH control, in "type I familial hyperaldosteronism" (dexamethasone suppressible). In "apparent MC excess syndrome", peripheral conversion of cortisol to cortisone is impaired by lack of 11β-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the "backdoor pathway", through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.

Quantitative standardization of pharmacologically active components from antiplasmodial plant Solanum nudum Dunal (wild and in vitro) / Estandarización cuantitativa de componentes farmacológicamente activos de la planta antiplasmodial Solanum nudum Dunal (silvestre e in vitro)

Solanum nudum Dunal (Solanaceae) is most commonly known andused by the population of the colombian Pacific coast as an antimalarial treatment. This article study into optimization and quantitative analysis of compounds steroidal over time of development of this species when grown in vitro and wild. A new steroidal compound named SN6 was elucidated by NMR and a new method of quantification of seven steroidal compounds (Diosgenone DONA and six steroids SNs) using HPLC-DAD-MS in extracts of cultures in vitroand wild was investigated. Biology activity of extracts was found to a range of antiplasmodial activity in FCB2 and NF-54 with inhibitory concentration (IC50) between (17.04 -100µg/mL) and cytotoxicity in U-937 of CC50 (7.18 -104.7µg/mL). This method creates the basis for the detection of seven sterols antiplasmodial present in extracts from S. nudum plant as a quality parameter in the control and expression of phytochemicals.

Solanum nudum Dunal (Solanaceae) es el más conocido y utilizado por la población de la costa del Pacífico colombiano como tratamiento antipalúdico. Este artículo estudia la optimización y el análisis cuantitativo de compuestos esteroides a lo largo del tiempo de desarrollo de esta especie cuando se cultiva in vitro y en forma silvestre. Un nuevo compuesto esteroideo llamado SN6 fue dilucidado por RMN y se investigó un nuevo método de cuantificación de siete compuestos esteroides (Diosgenone DONA y seis esteroides SN) usando HPLC-DAD-MS en extractos de cultivos in vitro y silvestres. La actividad biológica de los extractos se encontró en un rango de actividad antiplasmodial en FCB2 y NF-54 con concentración inhibitoria (IC50) entre (17.04 -100 µg/mL) y citotoxicidad en U-937 de CC50 (7.18 -104.7 µg/mL). Este método crea la base para la detección de siete esteroles antiplasmodiales presentes en extractos de planta de S. nudum como parámetro de calidad en el control y expresión de fitoquímicos.

Directrices para el diagnóstico clínico y el tratamiento del Dengue, el Chikunguña y el Zika / Guidelines for the clinical diagnosis and treatment of Dengue, Chikungunya, and Zika

En la actualidad, las guías basadas en la evidencia constituyen una de las herramientas más útiles para mejorar la salud pública y la práctica clínica. Su finalidad es formular intervenciones con sólidas pruebas de eficacia, evitar riesgos innecesarios, utilizar los recursos de forma eficiente, disminuir la variabilidad clínica y, en esencia, mejorar la salud y garantizar una atención de calidad, razón de ser de los sistemas y servicios de salud. Las presentes directrices se elaboraron siguiendo la metodología GRADE con el apoyo de un panel de expertos clínicos de distintos países, todos ellos convocados por la Organización Panamericana de la Salud. Por medio de la respuesta a doce preguntas clave sobre el diagnóstico clínico y el tratamiento del dengue, el chikunguña y el zika, se formulan recomendaciones basadas en evidencia para pacientes pediátricos, jóvenes, adultos, personas mayores y embarazadas expuestos a estas enfermedades o con sospecha o diagnóstico confirmado de infección. La finalidad de las directrices es evitar la progresión a las formas graves y a los eventos mortales que puedan causar. Las recomendaciones están dirigidas a profesionales de la salud, incluidos el personal médico general, residente y especialista; y los profesionales de enfermería, así como a estudiantes de medicina y enfermería, quienes de una u otra forma participan en la atención de pacientes con sospecha de dengue, chikunguña o zika. También se dirige a los administradores de las unidades de salud y a los equipos directivos de los programas nacionales de prevención y control de enfermedades arbovirales, quienes tienen la responsabilidad de facilitar el proceso de aplicación de estas directrices. Esperamos que esta publicación beneficie no solo al personal de salud, que dispondrá de información científica actualizada y de la mejor calidad posible, sino a los menores, los adultos, las embarazadas, las personas mayores y la población en general, quienes recibirán una mejor atención de salud prestada por personal médico debidamente capacitado.

Evidence-based guidelines are one of the most useful tools for improving public health and clinical practice. Their purpose is to formulate interventions based on strong evidence of efficacy, avoid unnecessary risks, use resources efficiently, reduce clinical variability and, in essence, improve health and ensure quality care, which is the purpose of health systems and services. These guidelines were developed following the GRADE methodology, with the support of a panel of clinical experts from different countries, all convened by the Pan American Health Organization. By responding to twelve key questions about the clinical diagnosis and treatment of dengue, chikungunya, and Zika, evidence-based recommendations were formulated for pediatric, youth, adult, older adult, and pregnant patients who are exposed to these diseases or have a suspected or confirmed diagnosis of infection. The purpose of the guidelines is to prevent progression to severe forms of these diseases and the fatal events they may cause. The recommendations are intended for health professionals, including general, resident, and specialist physicians, nursing professionals, and medical and nursing students, who participate in caring for patients with suspected dengue, chikungunya, or Zika. They are also intended for health unit managers and the executive teams of national arboviral disease prevention and control programs, who are responsible for facilitating the process of implementing these guidelines.

Hiperglicemia y diabetes inducidas por esteroides / Hyperglycemia and steroid-induced diabetes

La hiperglicemia y/o diabetes inducida por esteroides, se define como la elevación de la glicemia, causada por la acción de los fármacos glucocorticoideos, sobre el metabolismo de los carbohidratos, y presenta una prevalencia entre un 20% al 50%, en pacientes sin diabetes previa, existiendo mayor riesgo para esta patología en pacientes con diabetes pre-existente, obesidad, uso crónico de esteroides o en dosis altas, entre otros. El diagnóstico se rige por los criterios para diabetes en la mayoría de los casos. No obstante, existen casos en donde la hiperglicemia por esteroides es sub-diagnosticada. Su manejo se basa en el tratamiento farmacológico (antidiabéticos orales, subcutáneos e insulina) y no farmacológico (dieta y ejercicio), tomando en cuenta, el patrón glicémico, peso, edad, co-morbilidades, dosis, tipo y tiempo de uso de los esteroides. La relevancia de conocer como diagnosticar y tratar dicha patología, se debe al riesgo de ingreso hospitalario, de infección, de mala cicatrización y de mortalidad en casos no tratados. En vista del aumento del uso de glucocorticoides en la actualidad, se hace una revisión del abordaje terapéutico de la hiperglicemia y diabetes inducida por esteroides.

Hyperglycemia and Steroid-induced Diabetes is defined as the elevation of glycemia caused by the action of glucocorticoid drugs on carbohydrate metabolism, with a prevalence between 20% and 50% in patients without Diabetes. Though, there is a greater risk of this pathology in patients with pre-existing Diabetes, Obesity, chronic use of steroids or in high doses, among others. In most cases, the diagnosis is governed by the criteria of Diabetes; however, there are cases where hyperglycemia Steroid-induced is under-diagnosed. Its management is based on pharmacological treatment (oral and subcutaneous hypoglycemic agents and insulin) and non-pharmacological treatment (diet and exercise), in accordance with the glycemic pattern, weight, age, co-morbidities, dose, type and the duration of the use of steroid. The relevance of knowing how to diagnose and treat this pathology is the risk of hospital admission, infection, poor healing and mortality in untreated cases. In view of the increased use of glucocorticoids nowadays, a review is made about the therapeutic approach to hyperglycemia and steroid-induced Diabetes.

Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD / 中国实验血液学杂志

OBJECTIVE@#To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).@*METHODS@#We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).@*RESULTS@#Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).@*CONCLUSION@#We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

Steroids from Uncaria rhynchophylla / 中国中药杂志

Thirteen steroids(1-13) were isolated from the non-alkaloid constituents of Uncaria rhynchophylla by column chromatography on silica gel, ODS, Sephadex LH-20, and preparative HPLC chromatography, and their structures were elucidated by analyses of the MS and NMR spectral data. All the compounds were isolated from the genus Uncaria for the first time, and 1 was a new compound. The ~1H-NMR and ~(13)C-NMR data of two compounds(12 and 13) in deuteron-chloroform were completely assigned. This study enriched the steroid constituents of U. rhynchophylla and provided scientific references for the elucidation of active constituents and further development and utilization of U. rhynchophylla.

Efficacy of adrenocorticotropic hormone in children with frequently relapsing or steroid-dependent nephrotic syndrome / 中华儿科杂志

Objective: To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in children with frequently relapsing or steroid-dependent nephrotic syndrome. Methods: The clinical data of 38 children with frequently relapsing or steroid-dependent nephrotic syndrome who were admitted to the Department of Nephrology, the Children Hospital, Zhejiang University School of Medicine from January 2015 to December 2020 were retrospectively analyzed. The general information, clinical manifestations, laboratory data of the children and follow-up (till 12 months after treatment) were collected. The patients were divided into ACTH group and Glucocorticoid (GC) group according to treatment plan. Cumulative remission, average recurrence rate, GC dosage, height and weight change and peripheral blood CD19+B lymphocyte count were compared between the two groups to evaluate the efficacy and adverse reactions of ACTH. Fisher's exact test, t test or rank sum test was used for comparison between groups. Results: Among the 38 patients, 28 were male and 10 were female, aged 84 (24, 180) months; 19 were in ACTH group and 19 were in GC group. The cumulative remission rate of 12 months in ACTH group was higher than that in GC group (9/19 vs. 2/19,χ²=6.81,P=0.009), the average recurrence rate was lower than that in GC group ((0.7±0.8) vs. (1.7±1.1) times, t=-3.27, P=0.011), and the average dosage of GC was lower than that in GC group ((0.27±0.16) vs. (0.51±0.27) mg/(kg·d), t=-3.21, P=0.014). The increase in height was higher than that in the GC group (4 (3,5) vs. 3 (2, 3) cm/year, Z=2.58, P=0.010), and the peripheral blood CD19+B lymphocyte count was lower than that in the GC group ((223±149)×106 vs. (410±213)×106/L,t=-3.35, P=0.009). In safety, 19 cases had transient decreased urine volume, 7 cases had hyperglycemia, and 3 cases had hypertension during the infusion of ACTH, which could be relieved after drug withdrawal. Conclusion: ACTH has a better effect on children with frequently relapsing or steroid-dependent nephrotic syndrome, which can improve cumulative sustained remission rate, lower relapses rate and decrease the dosage of GC, with good safety.