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1.
Indian J Ophthalmol ; 71(2): 363-368, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36727321

RESUMO

Purpose: Our primary aim was to evaluate intraocular cytokines (IC) before and after dexamethasone in diabetic macular edema (DME). Our secondary aim was to study the early and late effects of single dexamethasone implant in DME. Methods: This before and after comparative study was conducted at the Department of Ophthalmology and Centre for Nanosciences at a quaternary referral center in Kerala, India, from September 2016 to September 2018. Patients underwent complete ophthalmological examination and cytokine analysis before and after dexamethasone implant. Levels of cytokines at baseline and repeat sample were studied. Results: Twenty-seven eyes (21 patients) were divided into two groups depending on time from baseline to second injection. Group 1 included patients with <3 months between the two samples - 12 (44.4%). Group 2 included patients with >3 months between the two samples -15 (55.6%). Best corrected visual acuity (BCVA) and central macular thickness (CMT) improved significantly post-dexamethasone in group 1, but not in group 2. Interleukin (IL)-4, IL-6, IL-10, vascular endothelial growth factor (VEGF), IL-1ß, interferon-gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and IL-2 decreased post-injection in group 1. But cytokines increased post-dexamethasone in group 2, except IL-10. When compared to baseline, IL-6 reduced to half in group 1 (P-value 0.814) and it tripled in group 2 ( P-value 0.009). The level of VEGF in the first and second samples was not different in either group. Conclusion: Our study suggests that dexamethasone acts more on IC than VEGF in DME. This is significant in the first 3 months with a rebound effect on IL-6 after 3 months. Our study also suggests that repeat injection of DEX in DME should be done at 3 months to prevent deterioration of visual acuity (VA) and worsening of CMT.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Glucocorticoides/uso terapêutico , Dexametasona/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Interleucina-10/uso terapêutico , Citocinas/metabolismo , Interleucina-6/uso terapêutico , Implantes de Medicamento , Injeções Intravítreas
2.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677648

RESUMO

Rheumatoid arthritis (RA) is a chronic, systemic immune disease that causes joint affection and even disability. Activated macrophages play an important role in the pathogenesis and progression of RA by producing pro-inflammatory factors. The use of dexamethasone (DXM) is effective in relieving the intractable pain and inflammatory progression of RA. However, long-term use of DXM is strongly associated with increased rates of diabetes, osteoporosis, bone fractures, and mortality, which hinders its clinical use. In this study, the dextran sulfate-cisaconitic anhydride-dexamethasone (DXM@DS-cad-DXM) micelles were prepared to treat RA by selectively recognizing scavenger receptor (SR) on the activated macrophages. The potent targeting property of DXM@DS-cad-DXM micelles to SR was by fluorescence microscope. Additionally, the effective accumulation and powerful anti-inflammatory activity of DXM@DS-cad-DXM micelles were observed in the inflamed joints of adjuvant-induced arthritis (AIA) rats after intravenous administration. Overall, DXM@DS-cad-DXM micelles are a potentially effective nanomedicine for targeted therapy of RA.


Assuntos
Artrite Reumatoide , Micelas , Ratos , Animais , Sulfato de Dextrana , Artrite Reumatoide/tratamento farmacológico , Macrófagos , Receptores Depuradores , Dexametasona
3.
Molecules ; 28(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36677745

RESUMO

Muscle atrophy caused by an imbalance between the synthesis and the degradation of proteins is a syndrome commonly found in the elders. Teaghrelin, a natural compound from oolong tea, has been shown to promote cell differentiation and to inhibit dexamethasone-induced muscle atrophy in C2C12 cells. In this study, the therapeutic effects of teaghrelin on muscle atrophy were evaluated in Sprague Dawley rats treated with dexamethasone. The masses of the soleus, gastrocnemius and extensor digitorum longus muscles were reduced in dexamethasone-treated rats, and the reduction of these muscle masses was significantly attenuated when the rats were supplemented with teaghrelin. Accordingly, the level of serum creatine kinase, a marker enzyme of muscle proteolysis, was elevated in dexamethasone-treated rats, and the elevation was substantially reduced by teaghrelin supplementation. A decrease in Akt phosphorylation causing the activation of the ubiquitin-proteasome system and autophagy for protein degradation was detected in the gastrocnemius muscles of the dexamethasone-treated rats, and this signaling pathway for protein degradation was significantly inhibited by teaghrelin supplementation. Protein synthesis via the mTOR/p70S6K pathway was slowed down in the gastrocnemius muscles of the dexamethasone-treated rats and was significantly rescued after teaghrelin supplementation. Teaghrelin seemed to prevent muscle atrophy by reducing protein degradation and enhancing protein synthesis via Akt phosphorylation.


Assuntos
Atrofia Muscular , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Dexametasona/efeitos adversos , Suplementos Nutricionais
4.
Hematology ; 28(1): 2156731, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36607147

RESUMO

OBJECTIVES: In the absence of head-to-head comparisons across relapsed/refractory multiple myeloma (RRMM) treatments following the approval of the oral proteasome inhibitor ixazomib, in combination with lenalidomide and dexamethasone (IRd), we conducted an indirect comparison of the efficacy of IRd relative to several RRMM therapies using Bayesian fixed-effects network meta-analysis (NMA) models. METHODS: Data for the NMA were obtained through a systematic literature review (conducted in June 2020), which identified randomized controlled trials (base case) and observational studies (extended network analysis) reporting overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: In the base case, IRd was associated with a significantly longer PFS than lenalidomide and dexamethasone (Rd), bortezomib monotherapy (V), dexamethasone (Dex), and pomalidomide and dexamethasone (Pom-dex), a significantly shorter PFS than daratumumab, lenalidomide, and dexamethasone (DRd), and a PFS comparable to elotuzumab, lenalidomide, and dexamethasone (ERd) and carfilzomib, lenalidomide, and dexamethasone (KRd). IRd was associated with a significantly longer OS than V, Dex, and Pom-dex, and an OS comparable to Rd, ERd, KRd, and DRd. The ORR of IRd was significantly higher than Rd, V, and Dex, significantly lower than KRd and DRd, and comparable to Pom-dex and ERd. The extended network analyses and sensitivity analyses were consistent with the base case. DISCUSSION: This NMA shows that IRd is relatively efficacious among RRMM treatments. Being an oral regimen, IRd is also convenient to manage. CONCLUSION: IRd could be a preferable treatment option for many patients with RRMM, particularly those seeking an efficacious and convenient therapeutic option.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiplo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Teorema de Bayes , Dexametasona/uso terapêutico , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Metanálise em Rede , Revisões Sistemáticas como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto
6.
PLoS One ; 18(1): e0280079, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649371

RESUMO

BACKGROUND: The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. METHODS: Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. FINDINGS: Of 1265 patients, high risk of HI (high HI5-NEWS2) (n = 367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n = 455, 36.0%). An intermediate risk group (n = 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p = 0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p = 0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p = 0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p = 0.31). INTERPRETATION: Higher HI5-NEWS2 scores measured at COVID-19 diagnosis, strongly associate with increased mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention in all cases.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Teste para COVID-19 , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico
7.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678312

RESUMO

Vitamin A has a key role in lung development and its deficiency is associated with an increased risk of bronchopulmonary dysplasia. This secondary cohort analysis of the ImNuT trial (Immature, Nutrition Therapy NCT03555019) aimed to (1) explore vitamin A status in preterm infants <29 weeks gestation and (2) assess the influence of inflammation and postnatal dexamethasone exposure on vitamin A concentrations in blood. We report detailed information on vitamin A biochemistry, vitamin A intake, markers of inflammation and dexamethasone exposure. After four weeks of age, infants exposed to dexamethasone (n = 39) showed higher vitamin A concentrations compared to unexposed infants (n = 41); median (IQR) retinol was 1.0 (0.74, 1.5) vs. 0.56 (0.41, 0.74) µmol/L, p < 0.001. Pretreatment retinol concentrations were lower in the dexamethasone group compared to non-exposed infants (p < 0.001); 88% vs. 60% of the infants were considered deficient in vitamin A (retinol < 0.7 µmol/L) at one week of age. Small size for gestational age, mechanical ventilation and elevated levels of interleukin-6 were factors negatively associated with first-week retinol concentrations. In conclusion, preterm infants <29 weeks gestation are at risk of vitamin A deficiency despite intakes that accommodate current recommendations. The presence of inflammation and dexamethasone exposure should be considered when interpreting vitamin A status.


Assuntos
Recém-Nascido Prematuro , Vitamina A , Lactente , Recém-Nascido , Humanos , Glucocorticoides/efeitos adversos , Inflamação/induzido quimicamente , Dexametasona/efeitos adversos
8.
Cochrane Database Syst Rev ; 1: CD013782, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688471

RESUMO

BACKGROUND: Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review. OBJECTIVES: To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022.  SELECTION CRITERIA: We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables.  MAIN RESULTS: We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear. Comparison 1: corticosteroids compared with placebo Participant-reported fatigue relief The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence). Serious adverse events There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Quality of lIfe One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence).  Comparison 2: corticosteroids compared with active comparator (modafinil) Participant-reported fatigue relief There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence).  Serious adverse events There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence).  Quality of lIfe One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Adulto , Adolescente , Modafinila , Corticosteroides/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Dexametasona/efeitos adversos , Fadiga/tratamento farmacológico , Fadiga/etiologia
9.
Theriogenology ; 198: 256-263, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623428

RESUMO

This study evaluated the relationship between the steroidal anti-inflammatory action of dexamethasone treatment in primiparous sows and farrowing and piglet performance in the first 5 d of life. For this purpose, 234 gilts were selected on the day of farrowing and distributed among three treatments: CON - control, without dexamethasone treatment; DexaPF - treatment with dexamethasone (20 mg im) per female at the moment of copious colostrum secretion (pre-farrowing); and DexaFO - treatment with dexamethasone (20 mg im), per female when the first piglet was born (farrowing onset). All females and their litters were evaluated regarding farrowing duration, obstetric interventions, colostrum yield and intake, newborn piglet traits, and piglet performance until 5 d of age. A subsample of 79 females (∼26 per treatment) had their blood glucose concentration evaluated hourly shortly after the first piglet was born until the end of farrowing. Additionally, blood samples from 11 litters per treatment were collected for immunocrit evaluation. As a result, faster farrowing was observed in the DexaPF treatment (188.14 min; P = 0.002) compared with CON (229.99 min) and DexaFO (221.79 min). Additionally, lower obstetric intervention rates were observed in sows treated with dexamethasone (DexaPF = 7.69%; DexaFO = 5.13%) compared with CON (19.23%; P = 0.02). The sow's blood glucose concentration during farrowing was higher in DexaPF (90.55 mg/dL) than in CON (73.15 mg/dL) and DexaFO (80.06 mg/dL) treatments (P < 0.01). Besides the effect on farrowing duration, no differences among treatments were observed regarding piglets born alive and stillbirths, newborn piglet vitality, colostrum consumption, immunocrit, and colostrum yield (P ≥ 0.17). Regarding piglet traits, higher percentages of piglets born without meconium staining and lower percentages of piglets with meconium scores 2 and 3 were observed in the groups treated with dexamethasone (DexaPF and DexaFO; P < 0.01) compared with CON. However, piglet weight gain and survival rate until 5 d of age were not affected by the treatment (P ≥ 0.61). In summary, dexamethasone treatment before farrowing onset, in primiparous sows, had the potential to reduce the farrowing duration and the necessity of obstetric intervention, but it did not affect the main productive parameters such as the occurrence of stillbirths, piglet weight gain, and survival rates until 5 d of age.


Assuntos
Natimorto , Doenças dos Suínos , Gravidez , Animais , Suínos , Feminino , Animais Recém-Nascidos , Natimorto/veterinária , Glicemia , Parto , Colostro , Sus scrofa , Aumento de Peso , Dexametasona , Lactação
11.
Cochrane Database Syst Rev ; 1: CD001955, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626194

RESUMO

BACKGROUND: Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018. OBJECTIVES: To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below. SEARCH METHODS: We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events). DATA COLLECTION AND ANALYSIS: Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias.  Any glucocorticoid compared to placebo  Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence).  One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children).  Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone.  There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review. AUTHORS' CONCLUSIONS: The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.


Assuntos
Crupe , Infecções Respiratórias , Criança , Humanos , Crupe/tratamento farmacológico , Dexametasona/uso terapêutico , Epinefrina/uso terapêutico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente
12.
Cells ; 12(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36672229

RESUMO

The NLRP3 inflammasome is a multimolecular complex that processes inactive IL-1ß and IL-18 into proinflammatory cytokines. OLT1177 is an orally active small compound that specifically inhibits NLRP3. Here, B16F10 melanoma were implanted in mice and treated with OLT1177 as well as combined with the glucocorticoid dexamethasone. At sacrifice, OLT1177 treated mice had significantly smaller tumors compared to tumor-bearing mice treated with vehicle. However, the combined treatment of OLT1177 plus dexamethasone revealed a greater suppression of tumor growth. This reduction was accompanied by a downregulation of nuclear and mitochondrial STAT3-dependent gene transcription and by a significant reduction of STAT3 Y705 and S727 phosphorylations in the tumors. In vitro, the human melanoma cell line 1205Lu, stimulated with IL-1α, exhibited significantly lower levels of STAT3 Y705 phosphorylation by the combination treatment, thus affecting the nuclear functions of STAT3. In the same cells, STAT3 serine 727 phosphorylation was also lower, affecting the mitochondrial functions of STAT3. In addition, metabolic analyses revealed a marked reduction of ATP production rate and glycolytic reserve in cells treated with the combination of OLT1177 plus dexamethasone. These findings demonstrate that the combination of OLT1177 and dexamethasone reduces tumor growth by targeting nuclear as well as mitochondrial functions of STAT3.


Assuntos
Melanoma , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Melanoma/tratamento farmacológico , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Fator de Transcrição STAT3/metabolismo
13.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674678

RESUMO

Since depression produces a long-term negative impact on quality of life, understanding the pathophysiological changes implicated in this disorder is urgent. There is growing evidence that demonstrates a key role for dysfunctional energy metabolism in driving the onset of depression; thus, bioenergetic alterations should be extensively studied. Brain metabolism is known to be a glucocorticoid-sensitive process, but the long-lasting consequences in adulthood following high levels of glucocorticoids at the early stages of life are unclear. We examined a possible association between brain energetic changes induced by synthetic glucocorticoid-dexamethasone treatment in the prenatal period and depressive-like behavior. The results show a reduction in the oxidative phosphorylation process, Krebs cycle impairment, and a weakening of the connection between the Krebs cycle and glycolysis in the frontal cortex of animals receiving dexamethasone, which leads to ATP reduction. These changes appear to be mainly due to decreased expression of pyruvate dehydrogenase, impairment of lactate transport to neurons, and pyruvate to the mitochondria. Acute stress in adulthood only slightly modified the observed alterations in the frontal cortex, while in the case of the hippocampus, prenatal exposure to dexamethasone made this structure more sensitive to future adverse factors.


Assuntos
Glucocorticoides , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Gravidez , Humanos , Glucocorticoides/metabolismo , Dexametasona/efeitos adversos , Dexametasona/metabolismo , Depressão/metabolismo , Qualidade de Vida , Encéfalo/metabolismo , Homeostase , Piruvatos/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo
15.
Lancet Oncol ; 24(2): 139-150, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36642080

RESUMO

BACKGROUND: Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population. METHODS: This study is an interim analysis of ATLAS, which is an investigator-initiated, multicentre, open-label, randomised, phase 3 trial in 12 academic and clinical centres in the USA and Poland. Participants were aged 18 years or older with newly diagnosed multiple myeloma, completed any type of induction and had stable disease or better, autologous stem-cell transplantation within 100 days, initiated induction 12 months before enrolment, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) using permuted blocks of sizes 4 and 6 and a web-based system to receive up to 36 cycles of carfilzomib, lenalidomide, and dexamethasone (28-day cycles of carfilzomib 20 mg/m2 administered intravenously in cycle one on days 1 and 2 then 36 mg/m2 on days 1, 2, 8, 9, 15, and 16 in cycles one to four and 36 mg/m2 on days 1, 2, 15, and 16 from cycle five up to 36 [per protocol]; lenalidomide 25 mg administered orally on days 1-21; and dexamethasone 20 mg administered orally on days 1, 8, 15, and 22) or lenalidomide alone (10 mg administered orally for the first three cycles and then at the best tolerated dose [≤15 mg for 28 days in 28-day cycles]) until disease progression or unacceptable toxicity as maintenance therapy. After 36 cycles, patients in both treatment groups received lenalidomide maintenance. Randomisation was stratified by response to previous treatment, cytogenetic risk factors, and country. Investigators and patients were not masked to treatment allocation. Patients in the carfilzomib, lenalidomide, and dexamethasone group with no detectable minimal residual disease after cycle six (as per International Myeloma Working Group criteria) and standard-risk cytogenetics were switched to lenalidomide maintenance as of cycle nine. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all randomly assigned patients). Safety was analysed in all randomly assigned patients who received at least one dose of study treatment. This unplanned interim analysis was triggered by the occurrence of 59 (61%) of the expected 96 events for the primary analysis and the results are considered preliminary. This trial is registered with ClinicalTrials.gov, NCT02659293 (active, not recruiting) and EudraCT, 2015-002380-42. FINDINGS: Between June 10, 2016, and Oct 21, 2020, 180 patients were randomly assigned to receive either carfilzomib, lenalidomide, and dexamethasone (n=93) or lenalidomide alone (n=87; intention-to-treat population). The median age of patients was 59·0 years (IQR 49·0-63·0); 84 (47%) patients were female and 96 (53%) were male. With a median follow-up of 33·8 months (IQR 20·9-42·9), median progression-free survival was 59·1 months (95% CI 54·8-not estimable) in the carfilzomib, lenalidomide, and dexamethasone group versus 41·4 months (33·2-65·4) in the lenalidomide group (hazard ratio 0·51 [95% CI 0·31-0·86]; p=0·012). The most common grade 3 and 4 adverse events were neutropenia (44 [48%] in the carfilzomib, lenalidomide, and dexamethasone group vs 52 [60%] in the lenalidomide group), thrombocytopenia (12 [13%] vs six [7%]), and lower respiratory tract infections (seven [8%] vs one [1%]). Serious adverse events were reported in 28 (30%) patients in the carfilzomib, lenalidomide, and dexamethasone group and 19 (22%) in the lenalidomide group. One treatment-related adverse event led to death (respiratory failure due to severe pneumonia) in the carfilzomib, lenalidomide, and dexamethasone group. INTERPRETATION: This interim analysis provides support for considering carfilzomib, lenalidomide, and dexamethasone therapy in patients with newly diagnosed multiple myeloma who completed any induction regimen followed by autologous stem-cell transplantation, which requires confirmation after longer follow-up of this ongoing phase 3 trial. FUNDING: Amgen and Celgene (Bristol Myers Squibb).


Assuntos
Mieloma Múltiplo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Lenalidomida , Resultado do Tratamento , Dexametasona , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células , Transplante Autólogo
16.
Lasers Med Sci ; 38(1): 47, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680633

RESUMO

To investigate the effect of intravitreal dexamethasone (IVD) implant injection, which was used in the treatment of DME, on CVI and to investigate whether CVI can be used as a prognostic marker in the treatment of anti-VEGF resistant DME. A retrospective observational and comparative study. Twenty-five eyes of 25 patients with refractory diabetic macular edema who underwent intravitreal dexamethasone (IVD) implant and 50 eyes of 50 healthy patients were included in the study. Central macular thickness (CMT), subfoveal choroidal thickness (SFCT), luminal choroidal area (LCA), total choroidal area (TCA), stromal choroidal area (SCA), and choroidal vascularity index (CVI) were measured on optical coherence tomography. There was no significant difference between the groups in terms of age and gender. When the pre-treatment values in the IVD group were compared with the healthy group, LCA and SCA values were higher, and CVI ratios were lower in the IVD group compared to the control group. When baseline, 1st, and 3rd months after injection were compared, it was determined that there was a significant decrease in CMT and LCA. There was no statistically significant difference in SFCT, TCA, and CVI. There was a significant negative correlation between baseline CVI and 3rd month CMT after IVD (rho: - 0.643, p: 0.001). It was observed that the baseline and 1st month LCA values were significantly higher than the 3rd month. The choroidal vascular structure may be affected by IVD treatment. CVI may also have value as a prognostic marker in monitoring the response to treatment.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/tratamento farmacológico , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Corioide , Dexametasona/farmacologia , Tomografia de Coerência Óptica
17.
Eur J Med Res ; 28(1): 52, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707848

RESUMO

BACKGROUND: Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. METHODS: Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro. RESULTS: The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway. CONCLUSION: ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.


Assuntos
Nefropatias , Síndrome Nefrótica , Animais , Ratos , Dexametasona , Doxorrubicina , Hormônios , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/patologia , Fosfatidilinositol 3-Quinases/genética , Ratos Sprague-Dawley
18.
Pain Manag ; 13(2): 129-141, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36718798

RESUMO

Aim: To study the effect of epidural dexamethasone in postoperative pain management. Methods: Random-effects meta-analysis was conducted in RevMan 5.4. Results: We included nine randomized-controlled trials (RCT) with 657 patients. Dexamethasone demonstrated longer analgesia duration (mean difference 266.18 minutes, 95% CI [3.21,529.14]; p 0.05), lower incidence of nausea and vomiting during the first postoperative day (risk ratio 0.36, 95% CI [0.18,0.71]; p 0.004), and lower antiemetic requirements (risk ratio 0.33, 95% CI [0.14,0.79]; p 0.01). No difference in pain reduction and the length of hospital stay was observed between the groups. Conclusion: Dexamethasone was associated with a longer analgesic effect, a lower number of patients requiring antiemetics, and lower incidences of nausea and vomiting.


Pain after major surgeries can be severe. Sometimes patients need to take additional analgesics after surgery. Dexamethasone is a steroid, which can potentially reduce this pain and the need for pain-relieving medications. We wanted to know whether dexamethasone reduces the use of analgesics, nausea and vomiting after surgeries, pain, or length of hospital stay. We found nine articles with 657 patients, which compared dexamethasone with a placebo. According to our analysis, dexamethasone does not decrease pain or length of hospital stay. However, surgery patients can benefit from a decrease in nausea and vomiting and the need for medications for these side effects. Due to the small number of participants, our conclusions should be taken with caution.


Assuntos
Analgesia , Antieméticos , Humanos , Náusea e Vômito Pós-Operatórios , Antieméticos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dexametasona/uso terapêutico
19.
Immun Inflamm Dis ; 11(1): e755, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36705410

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) complicated by multiple myeloma (MM) is a relatively rare clinical presentation, and is easily ignored due to their similar or even identical manifestation, which may lead to misdiagnosis and mistreatment. CASE REPORT: We report two cases of SLE with MM. Case 1 was a 59-year-old male who was diagnosed with SLE 11 years ago. Abnormal kidney function was detected 4 months ago and a bone marrow aspirate revealed MM. He then received three cycles of bortezomib, dexamethasone, and chemotherapy with liposomal doxorubicin, and one cycle of lenalidomide plus dexamethasone. He died of infectious shock. Case 2 was a 58-year-old female who was diagnosed with SLE 27 years ago. After the onset of abnormal renal function 4 years ago, the patient was still treated according to SLE disease activity. When renal function rapidly deteriorated, serum and urine immunofixation electrophoresis was positive for IgG γ with free light chains and she was diagnosed with SLE complicated by MM. She did not agree to the treatment for MM as advised and was discharged from the hospital against medical advice. Case 2 died of cardiac failure. Thirteen cases of SLE with MM reported from 2000 to 2022 in PUBMED and Mendeley and our above two cases were reviewed. Among the 15 patients, 13 were females and 2 were males. The median age at the time of SLE with MM diagnosis was 50 years, and the median time to a delayed diagnosis was 7 years. The serum monoclonal immunoglobulin level was elevated and extramedullary manifestations of renal dysfunction were common. CONCLUSIONS: An elevated monoclonal immunoglobulin level or newly unexplained renal dysfunction occurring in a patient with SLE should prompt monitoring and further screening of MM, rather than treatment as a secondary manifestation of SLE.


Assuntos
Nefropatias , Lúpus Eritematoso Sistêmico , Mieloma Múltiplo , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Bortezomib/uso terapêutico , Dexametasona , Nefropatias/complicações , Nefropatias/tratamento farmacológico
20.
J Int Adv Otol ; 19(1): 10-15, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36718030

RESUMO

BACKGROUND: Stress could be a contributing cause of sudden hearing loss. This study intended to develop an animal model of stress-induced sudden hearing loss and to evaluate the effects of dexamethasone. METHODS: Two stress models (I and II) for rats were designed using various stressors and modified by adjusting the stress protocol to increase the threshold significantly. For the stress model with a significant increase in threshold after stress exposure, changes in cortisol levels according to stress exposure were measured. The threshold shift and the change in the cellular structure associated with stress exposure and dexamethasone administration were analyzed. RESULTS: While hearing thresholds increased only at 16 kHz in rats of stress model I (n=10), the thresholds increased at 16 and 32 kHz in rats of stress model II (n=16). Cortisol level increased after stress exposure (P = .015) in stress model II. Among stress model II rats (stress only and stress+dexamethasone groups), the threshold shift at 16 kHz significantly decreased 1 day after dexamethasone injection in the stress+dexamethasone group (n=8). Histologically, the cochlear cellularity of the stress+dexamethasone group was more compact than that of the stressonly group (n=8). CONCLUSION: Our preliminary study presented the development of an animal model of stress-induced sudden hearing loss and the positive results of steroids in terms of hearing recovery.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Ratos , Animais , Dexametasona/farmacologia , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/etiologia , Hidrocortisona/farmacologia , Audição , Cóclea/patologia , Perda Auditiva Neurossensorial/patologia , Resultado do Tratamento , Glucocorticoides
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