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1.
BMJ ; 377: o1302, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688460

RESUMO

The studyHutchinson P, Edlmann E, Bulters D, et al. Trial of dexamethasone for chronic subdural haematoma. N Engl J Med 2020;383:2616-27.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/dexamethasone-should-not-be-used-chronic-subdural-haematoma/.


Assuntos
Hematoma Subdural Crônico , Dexametasona/efeitos adversos , Hematoma Subdural Crônico/tratamento farmacológico , Humanos
2.
BMJ Open ; 12(6): e059553, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705335

RESUMO

INTRODUCTION: Postnatal steroids during the first few weeks of life have been demonstrated to be effective in decreasing the incidence of bronchopulmonary dysplasia (BPD), a serious chronic respiratory condition affecting preterm infants. However, this preventive option is limited by the concern of neurological side effects. Steroids are used to treat established BPD in an attempt to reduce mortality, and length of stay and home oxygen therapy, both of which associated with high levels of parental stress and healthcare costs. Moreover, a late timing for steroid treatment may show a more favourable safety profile in terms of neurodevelopment outcomes, considering the added postnatal brain maturation of these infants. Here, we report a protocol for a systematic review, which aims to determine the efficacy and long-term safety of postnatal steroids for the treatment of established BPD in preterm infants. METHODS AND ANALYSIS: MEDLINE, Embase, Cochrane databases and sources of grey literature for conference abstracts and trial registrations will be searched with no time or language restriction. We will include case-control studies, cohort studies and non-randomised or randomised trials that evaluate postnatal steroids for infants diagnosed with moderate or severe established BPD at 36 weeks' postmenstrual age. We will pool data from studies that are sufficiently similar to make this appropriate. Data extraction forms will be developed a priori. Observational studies and non-randomised and randomised clinical trials will be analysed separately. We will combine OR with 95% CI for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes. We will account for the expected heterogeneity by using a random-effects model. We will perform subgroup analysis based on the a priori determined covariate of interest. ETHICS AND DISSEMINATION: Systematic reviews are exempted from approval by an ethics committee. Attempts will be sought to publish all results. PROSPERO REGISTRATION NUMBER: CRD42021218881.


Assuntos
Displasia Broncopulmonar , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/prevenção & controle , Dexametasona/efeitos adversos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Metanálise como Assunto , Revisões Sistemáticas como Assunto
3.
Pediatr Emerg Care ; 38(6): e1285-e1290, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35507383

RESUMO

OBJECTIVE: The purpose of this study was to compare the efficacy of a single dose of dexamethasone to 2 doses of dexamethasone in treating mild to moderate asthma exacerbations in pediatric patients. We anticipated that there would not be a difference in the rate of return visits to the emergency department (ED), urgent care, or primary care physician for continued asthma symptoms. METHODS: This was a prospective, randomized, single-center, unblinded, parallel-group randomized clinical trial of patients 2 to 20 years old presenting to a pediatric ED with mild to moderate asthma exacerbations. The patients were randomized to receive 1 or 2 doses of dexamethasone (0.6 mg/kg per dose, maximum of 16 mg). Telephone follow-up interviews were performed on the sixth day after ED visit. The primary outcome measures were return visits to either primary care physician or ED for continued asthma symptoms. Secondary outcomes were days of symptoms, missed school days, and adverse effects. RESULTS: Of the 318 children initially enrolled, 308 patients met the enrollment criteria. These patients were randomized into 2 groups. There were 116 patients in group 1 and 116 patients in group 2. There was no significant difference between groups regarding return visits (group 1, 12.1%; group 2, 10.3%; odds ratio [OR], 0.892 [95% confidence interval {CI}, 0.377-2.110]), days to symptom resolution (group 1, 2.4; group 2, 2.5; OR, 0.974 [95% 95% CI, 0.838-1.132]), missed school days (group 1, 47%; group 2, 51%; OR, 1.114 [95% CI, 0.613-2.023]), or vomiting (group 1, 8.6%; group 2, 3.4%; OR, 2.424 [95% CI, 0.637-9.228]). CONCLUSIONS: In this single-center, unblinded randomized trial of children and adolescents with mild to moderate acute exacerbations of asthma, there was no difference in the rate of return visits for continued or worsened symptoms between patients randomized to 1 or 2 doses of dexamethasone.


Assuntos
Asma , Adolescente , Adulto , Asma/tratamento farmacológico , Criança , Pré-Escolar , Dexametasona/efeitos adversos , Serviço Hospitalar de Emergência , Humanos , Estudos Prospectivos , Adulto Jovem
4.
Anticancer Res ; 42(6): 3117-3123, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35641271

RESUMO

BACKGROUND/AIM: Nausea and vomiting are two of the most distressing adverse events of cancer radiotherapy. The aim of this study was to examine the control rate and risk factors associated with nausea and vomiting in patients with cervical cancer receiving radiotherapy. PATIENTS AND METHODS: This retrospective study examined patients with cervical cancer who received radiotherapy alone or with concomitant cisplatin. Patients who received radiotherapy alone were not administered antiemetic premedication, while patients who received radiotherapy with concomitant weekly cisplatin (40 mg/m2) were administered antiemetic therapy comprising granisetron and dexamethasone. Risk factors for non-complete response (CR) were identified using multivariate logistic regression analysis. RESULTS: Multivariate analysis indicated that younger age and concomitant weekly cisplatin were significant factors associated with non-CR across 5 weeks of treatment in patients who received radiotherapy. The proportion achieving CR among younger patients (<65 years) who received radiotherapy alone or with concomitant cisplatin was significantly lower than that among older patients (≥65 years) (Concomitant cisplatin: 27% vs. 67%, p=0.049; Radiotherapy alone: 62% vs. 91%, p=0.166). However, the proportion of patients achieving CR across 5 weeks of treatment was insufficient in all groups except for those aged ≥ 65 years who received radiotherapy alone. CONCLUSION: Antiemetic prophylaxis should be considered for younger patients with cervical cancer undergoing radiotherapy alone. Further, neurokinin-1 receptor antagonist should be added to 5-hydroxytryptamine type-3 receptor antagonist and dexamethasone as antiemetic prophylactic therapy for patients with cervical cancer undergoing radiotherapy with concomitant weekly doses of 40 mg/m2 cisplatin.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias do Colo do Útero , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Cisplatino/efeitos adversos , Dexametasona/efeitos adversos , Feminino , Humanos , Náusea/tratamento farmacológico , Náusea/etiologia , Náusea/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Vômito/induzido quimicamente , Vômito/prevenção & controle
5.
Mar Drugs ; 20(5)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35621931

RESUMO

The in vitro capacity of Ishige okamurae extract (IO) to improve impaired muscle function has been previously examined. However, the mechanism underlying IO-mediated muscle protein metabolism and the role of its component, Ishophloroglucin A (IPA), in mice with dexamethasone (Dexa)-induced muscle atrophy remains unknown. In the present study, we evaluated the effect of IO and IPA supplementation on Dexa-induced muscle atrophy by assessing muscle protein metabolism in gastrocnemius and soleus muscles of mice. IO and IPA supplementation improved the Dexa-induced decrease in muscle weight and width, leading to enhanced grip strength. In addition, IO and IPA supplementation regulated impaired protein synthesis (PI3K and Akt) or degradation (muscle-specific ubiquitin ligase muscle RING finger and atrogin-1) by modulating mRNA levels in gastrocnemius and soleus muscles. Additionally, IO and IPA upregulated mRNA levels associated with muscle growth activation (transient receptor potential vanilloid type 4 and adenosine A1 receptor) or inhibition (myostatin and sirtuin 1) in gastrocnemius and soleus muscle tissues of Dexa-induced mice. Collectively, these results suggest that IO and IO-derived IPA can regulate muscle growth through muscle protein metabolism in Dexa-induced muscle atrophy.


Assuntos
Misturas Complexas , Proteínas Musculares , Atrofia Muscular , Feófitas , Animais , Benzofuranos , Misturas Complexas/farmacologia , Misturas Complexas/uso terapêutico , Dexametasona/efeitos adversos , Dioxinas , Camundongos , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Feófitas/metabolismo , RNA Mensageiro/metabolismo
6.
J Infect ; 85(1): 57-63, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35605805

RESUMO

OBJECTIVES: To determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients, and the impact of dexamethasone as standard therapy. METHODS: This multicentre, observational, retrospective study included patients ≥ 18 years admitted from March 1st 2020 to January 31st 2021 with COVID-19 infection who received mechanical ventilation. Patient characteristics, clinical characteristics, therapy and survival were examined. RESULTS: 155/156 patients (115 men, mean age 62 years, range 26-84 years) were included. 67 patients (43%) had 90 superinfections, pneumonia dominated (78%). Superinfections were associated with receiving dexamethasone (66% vs 32%, p<0.0001), autoimmune disease (18% vs 5.7%, p<0.016) and with longer ICU stays (26 vs 17 days, p<0,001). Invasive fungal infections were reported exclusively in dexamethasone-treated patients [8/67 (12%) vs 0/88 (0%), p<0.0001]. Unadjusted 90-day survival did not differ between patients with or without superinfections (64% vs 73%, p=0.25), but was lower in patients receiving dexamethasone versus not (58% vs 78%, p=0.007). In multiple regression analysis, superinfection was associated with dexamethasone use [OR 3.7 (1.80-7.61), p<0.001], pre-existing autoimmune disease [OR 3.82 (1.13-12.9), p=0.031] and length of ICU stay [OR 1.05 p<0.001]. CONCLUSIONS: In critically ill COVID-19 patients, dexamethasone as standard of care was strongly and independently associated with superinfections.


Assuntos
Doenças Autoimunes , COVID-19 , Superinfecção , Corticosteroides/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/etiologia , Dexametasona/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Superinfecção/etiologia
7.
Nutrients ; 14(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35565825

RESUMO

The present study aimed to investigate the effects of monotropein (MON) on improving dexamethasone (DEX)-induced muscle atrophy in mice and C2C12 mouse skeletal muscle cells. The body weights, grip strengths, and muscle weights of mice were assessed. The histological change in the gastrocnemius tissues was also observed through H&E staining. The expression of myosin heavy chain (MyHC), muscle ring finger 1 (MuRF1), and muscle atrophy F-box (Atrogin1) and the phosphorylation of AKT, mTOR, and FOXO3a in the muscle tissues of mice and C2C12 myotubes were analyzed using Western blotting. MON improved muscle atrophy in mice and C2C12 myotubes by regulating catabolic states via the AKT/mTOR/FOXO3a signaling pathways, and enhanced muscle function by the increases of muscle mass and strength in mice. This suggests that MON could be used for the prevention and treatment of muscle atrophy in patients.


Assuntos
Dexametasona , Proteínas Proto-Oncogênicas c-akt , Dexametasona/efeitos adversos , Humanos , Iridoides , Fibras Musculares Esqueléticas , Músculo Esquelético/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
8.
Nutrients ; 14(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35565830

RESUMO

Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle atrophy. Previous studies have shown beneficial effects of genistein treatment on muscle mass and muscle atrophy, but the mechanism is not fully understood. Differential co-expression network analysis revealed that miR-222 was upregulated in multiple skeletal muscle atrophy models. Subsequent in vitro (C2C12 myoblasts) and in vivo (C57BL/6 mice) experiments showed that genistein could alleviate dexamethasone-induced muscle atrophy and downregulate the expression of miR-222 in muscle tissue and C2C12 myotubes. The dual-luciferase reporter assay system confirmed that IGF1 is a target gene of miR-222 and is regulated by genistein. In C2C12 myotubes, both dexamethasone and miR-222 overexpression promoted muscle atrophy, however, this function was significantly reduced after genistein treatment. Furthermore, we also observed that both genistein and miR-222 antagomiR could significantly inhibit dexamethasone-induced muscle atrophy in vivo. These results suggest that miR-222 may be involved in the regulation of genistein on muscle atrophy, and genistein and miR-222 may be used to improve muscle health.


Assuntos
Genisteína , MicroRNAs , Animais , Linhagem Celular , Dexametasona/efeitos adversos , Genisteína/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Fibras Musculares Esqueléticas , Músculo Esquelético/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/genética
9.
J Orthop Surg Res ; 17(1): 290, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619183

RESUMO

PURPOSE: To investigate whether a cocktail therapy of dexamethasone, ropivacaine, dexmedetomidine, and vitamin B12 can achieve satisfactory pain relief and promote early functional recovery after PPECD. METHODS: Eighty single-level patients with CDH who received PPECD were retrospectively divided into two groups: the cocktail and control groups. Clinical data were recorded and evaluated by a dedicated physician who was not involved in the patient's treatment. The primary clinical outcomes included visual analog scores (VASs) for upper limber pain and neck disability index (NDI) scores. The follow-up time points were preoperatively and postoperative 1 week, 1 month, 3 months, 6 months, and 12 months. The modified MacNab criteria was used to evaluate the surgical effect of the last follow-up. RESULTS: The follow-up data of 74 cases were complete, except 6 cases lost to follow-up. There was no significant difference between the two groups in demographics, duration of symptoms, operation stage (p > 0.05), and operation time (80.5 ± 5.5 vs. 81.5 ± 3.5 min). The VAS in the upper limbs pain was significantly higher postoperatively than preoperatively in both groups (p < 0.05). The cocktail group had a lower VAS than the control group 1 week postoperatively (p < 0.05); however, VAS not different between groups at the remaining time points. The NDI scores were significantly better postoperatively than preoperatively, and no significant differences were seen when comparing nodes at postoperative follow-up (p > 0.05). In the control group, two cases with foraminal stenosis were found to have unrelieved pain in the early postoperative period, but the pain was relieved at the final follow-up and did not convert to open decompression surgery. CONCLUSIONS: Cocktail treatment, in which a drug sustained-release material made of gelatin sponge was impregnated with dexamethasone, ropivacaine, dexmedetomidine and vitamin B12, facilitates pain relief and early postoperative recovery after PPECD.


Assuntos
Dexmedetomidina , Gelatina , Anti-Inflamatórios , Vértebras Cervicais/cirurgia , Dexametasona/efeitos adversos , Discotomia/efeitos adversos , Estudos de Viabilidade , Humanos , Dor/cirurgia , Estudos Retrospectivos , Ropivacaina , Resultado do Tratamento , Vitamina B 12
10.
Sci Rep ; 12(1): 8299, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585182

RESUMO

In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing. There were 199 (118 up-regulated; 81 down-regulated) and 525 (119 up-regulated; 406 down-regulated) DEGs in 16 h and 7 d treatment groups respectively. The unique genes identified in 16 h and 7 d treatment groups were 152 and 478 respectively. This study found a distinct gene signature and pathways between two treatment regimes. Longer exposure of DEX treatment showed a dys-regulation of Wnt and Rap1 signaling and so highlighted potential therapeutic targets for pharmacological management of GC-OHT/glaucoma.


Assuntos
Glaucoma , Malha Trabecular , Células Cultivadas , Dexametasona/efeitos adversos , Glaucoma/induzido quimicamente , Glaucoma/tratamento farmacológico , Glaucoma/genética , Glucocorticoides/metabolismo , Humanos , Malha Trabecular/metabolismo , Transcriptoma
11.
Probl Endokrinol (Mosk) ; 68(2): 56-65, 2022 02 22.
Artigo em Russo | MEDLINE | ID: mdl-35488757

RESUMO

BACKGROUND: There is a lack of data on the features of dysglycemia in hospitalized patients with COVID-19 and concomitant diabetes mellitus (DM) confirmed by continuous glucose monitoring (CGM). AIM: to study the glycemic profile in hospitalized patients with COVID-19 and type 2 diabetes mellitus by continuous glucose monitoring and the role of steroid therapy in dysglycemiadevelopment. MATERIALS AND METHODS: We examined 21 patients with COVID-19 and DM 2 and 21 patients with DM 2 without COVID-19 (control group) using a professional 4-7-day CGM. We also compared two subgroups of patients with COVID-19 and DM 2: 1) patients received systemic glucocorticosteroids (GCS) during CGM and 2) patients in whomCGMwas performed after discontinuation of GCS. RESULTS: Compared with controls, patients with COVID-19 and DM2 had lesser values of glycemic «time in range¼ (32.7 ± 20.40 vs 48.0 ± 15.60%, p = 0.026) andhigher parameters of mean glycemia (p <0.05) but similar proportion of patients with episodes of hypoglycemia (33.3% vs 38.1%, p = 0.75). Patients who received dexamethasone during CGM were characterized by higher hyperglycemia and the absence of episodes of hypoglycemia. In patients who hadCGM after dexamethasone discontinuation, hyperglycemia was less pronounced, but 60% of them had episodes of hypoglycemia, often nocturnal, clinically significant and not detected by routine methods. CONCLUSION: Patients with COVID-19 and DM 2had severe and persistent hyperglycemia but a third of them hadalso episodes of hypoglycemia. During therapy with dexamethasone, they had the most pronounced hyperglycemia without episodes of hypoglycemia. In patients who underwent CGM after discontinuation of dexamethasone, hyperglycemia was less pronounced but 60% of them have episodes of hypoglycemia, often nocturnal, clinically significant and not diagnosed by routine methods. It would be advisable to recommend at least a 5-6-fold study of the blood glucose level (with its obligatory assessment at night) even for stable patients with COVID-19 and DM 2after the end of GCS treatment.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Hiperglicemia , Hipoglicemia , Glicemia , Automonitorização da Glicemia , COVID-19/complicações , COVID-19/tratamento farmacológico , Dexametasona/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Esteroides
12.
Mol Neurobiol ; 59(6): 3767-3777, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35396693

RESUMO

Prenatal exposure to dexamethasone (DEX) results in long-lasting effects on cognitive functions such as learning and memory impairment. However, the mechanisms underlying these DEX-induced deleterious effects are not well known. Here, we assessed whether cyclooxygenase-2 (COX-2) is involved in the impact of prenatal exposure to DEX on learning and memory during adulthood. Pregnant Sprague-Dawley rats received daily injections of either DEX (0.2 mg/kg; i.p.) or saline from gestation day (GD) 14 until GD21. Gene and protein expression of COX-2, as well as presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein-95) proteins, were monitored in the dorsal and ventral hippocampi of adult male and female offspring. A different cohort of adult male and female rat offspring was given daily injections of either vehicle or a specific COX-2 inhibitor (celecoxib 10 mg/kg, i.p.) for 5 consecutive days and was subsequently subjected to Morris water maze memory test. Prenatal DEX enhanced the expression of COX-2 protein and cox-2 mRNA in the dorsal hippocampus of adult female but not male rats. This enhanced COX-2 expression was associated with reduced expression in pre- and postsynaptic proteins and altered memory acquisition and retention. Administration of COX-2-specific inhibitor alleviated prenatal DEX-induced memory impairment in adult female rats. This study suggests that prenatal activation of glucocorticoid receptors stimulates COX-2 gene and protein expression and impairs hippocampal-dependent spatial memory in female but not male rat offspring. Furthermore, COX-2 selective inhibitors can be used to alleviate the long-lasting deleterious effects of corticosteroid medication during pregnancy.


Assuntos
Ciclo-Oxigenase 2 , Dexametasona , Efeitos Tardios da Exposição Pré-Natal , Receptores de Glucocorticoides , Animais , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dexametasona/efeitos adversos , Feminino , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo
13.
Exp Hematol ; 111: 79-86, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35417741

RESUMO

Identifying effective combination regimens is a high priority in multiple myeloma (MM), as most patients eventually become refractory to their current treatments. In this study, we investigated whether the proteasome inhibitor (PI) ixazomib could delay disease progression among patients who failed regimens containing another PI, bortezomib or carfilzomib. This phase 1/2, multicenter, open-label, nonrandomized study enrolled patients who were refractory to a previous regimen containing bortezomib or carfilzomib. Patients continued the other anti-MM drugs in the regimen at the same doses and frequencies. Patients with combination regimens with unknown maximum tolerated dose (MTD) of ixazomib were enrolled in phase 1, with ixazomib starting at 3 mg and then dose escalated to 4 mg. Patients on regimens with a known ixazomib MTD were enrolled in phase 2. Primary endpoints were overall response rate (ORR), clinical benefit rate (CBR), adverse events (AEs), and determination of maximum tolerated dose (MTD). Of the 46 patients enrolled, 39 were evaluable for efficacy. ORR and CBR were 12.8% and 17.9%, respectively. Ixazomib appeared to be well tolerated as a replacement for carfilzomib and bortezomib, with 23.9% of patients experiencing at least one grade ≥3 serious adverse event (SAE) and 37.0% experiencing at least one grade ≥3 AE. The most common grade ≥3 AEs were hyponatremia (8.7%), anemia (8.7%), dyspnea (8.7%), thrombocytopenia (6.5%), dehydration (4.3%), and pneumonia (4.3%). The results indicate that ixazomib is not an effective replacement for bortezomib or carfilzomib for patients with MM who have previously relapsed on other bortezomib/carfilzomib-containing regimens.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Boro , Bortezomib , Dexametasona/efeitos adversos , Glicina/análogos & derivados , Humanos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Oligopeptídeos
14.
Biomed Pharmacother ; 150: 112991, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35462336

RESUMO

Proton pump inhibitors (PPIs) are among the most commonly prescribed medicines for the management of acid-related gastrointestinal diseases. Osteonecrosis of the jaw (ONJ) is a serious adverse event that is associated with the use of antiresorptive and antiangiogenic agents. According to previous clinical reports, the use of PPIs contributes to the pathogenesis of severe ONJ that requires surgery. Here, we investigated the effects of lansoprazole (LP) or LP in combination with zoledronate (ZOL) on ONJ development in mice. C57BL/6J mice were administered ZOL (125 µg/kg intravenously, twice weekly) and/or LP (10 mg/kg intraperitoneally; 3 weeks of 3 consecutive days followed by 1 day off). One week after initiation of the study, the first molar was atraumatically extracted. Concurrently with ZOL administration, dexamethasone (Dex) was administered (5 mg/kg intraperitoneally, twice weekly). Micro-computed tomography and histological evaluation were performed to characterize femoral structures, tooth extraction sockets, and osteonecrosis areas. The results showed that ZOL/Dex significantly increased bone mass compared to saline/Dex, while the simultaneous administration of LP and ZOL/Dex diminished the ZOL-induced enhancement of bone mass. In the alveolar bone around the tooth extraction socket, necrotic bone was significantly increased in the LP/Dex group compared to the saline/Dex group. However, no signs of more severe ONJ-like lesions were observed following combined administration of LP and ZOL/Dex, other than an increase in the number of non-attached TRAP-positive cells. Our findings in a mouse model suggest that LP use can be a risk factor for the development of ONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/farmacologia , Dexametasona/efeitos adversos , Difosfonatos/farmacologia , Imidazóis , Lansoprazol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Extração Dentária/efeitos adversos , Alvéolo Dental/patologia , Microtomografia por Raio-X , Ácido Zoledrônico/farmacologia
15.
Nihon Shokakibyo Gakkai Zasshi ; 119(4): 332-341, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35400686

RESUMO

We examined 171 patients with novel coronavirus disease 2019 (COVID-19) with liver injury in the respiratory failure groups and the nonrespiratory failure groups and investigated 41 patients with moderate II COVID-19 with respiratory failure who received dexamethasone (Dex) monotherapy in the liver injury group and the nonliver injury group at the time before treatment. The respiratory failure group had 64% more liver damage than the nonrespiratory failure group, was older, had more men, and had significantly more complications from lifestyle-related diseases such as hypertension and diabetes. Obesity was more common in the liver injury group prior to Dex monotherapy, and the liver CT value was significantly lower than in the nonliver injury group. Liver injury worsened in 41% of patients after Dex monotherapy, but there was no significant difference in the frequency before Dex monotherapy between the liver injury group and the nonliver injury group, and the degree of liver injury was mild in all cases, improving in 38% of the liver injury group. Dex monotherapy was a safe treatment for moderate II COVID-19, which frequently resulted in liver injury.


Assuntos
COVID-19 , Insuficiência Respiratória , COVID-19/complicações , COVID-19/tratamento farmacológico , Dexametasona/efeitos adversos , Humanos , Fígado , Masculino
16.
Ann Hematol ; 101(6): 1211-1216, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35403851

RESUMO

Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a 5-HT3 receptor antagonist, Apr, and dexamethasone (Dex) for highly emetogenic chemotherapies. Apr inhibits CYP3A4 dose-dependently. Since Dex is metabolized by CYP3A4, the combined use of Apr and Dex inhibits Dex metabolism. CINV guidelines therefore recommend dose-reduction of Dex when Apr and Dex are used together. However, there is some controversy over whether or not Dex should be reduced when administered as an antitumor agent for lymphoid malignancies. We retrospectively compared the antitumor effect of Dex-containing chemotherapy in which Dex is administered at the usual dose without Apr (group A) or administered at a half-dose in combination with Apr (group B). We analyzed 62 consecutive patients with refractory or relapsed CD20 + B cell lymphoma who received R-DHAP therapy in our hospital, including 29 and 33 cases in groups A and B, respectively. The response rate at the end of the first course of R-DHAP was 62.1% and 54.5%, respectively (P = 0.61). As another endpoint to evaluate the effect of Dex, group B tended to show greater suppression of the lymphocyte count (P = 0.05). Therefore, decreasing the dose of Dex by half appeared to be reasonable when combined with Apr.


Assuntos
Antieméticos , Antineoplásicos , Linfoma , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Aprepitanto/efeitos adversos , Citocromo P-450 CYP3A , Dexametasona/efeitos adversos , Humanos , Linfoma/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Estudos Retrospectivos , Vômito/induzido quimicamente , Vômito/prevenção & controle
17.
Nagoya J Med Sci ; 84(1): 80-90, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35392014

RESUMO

More than 40% of Japanese patients with multiple myeloma (MM) are over 75 years of age at diagnosis. Regardless of the treatment benefits, complications and relapses obstruct long-term survival. We conducted a phase II, open-label, single-arm, multicenter clinical trial to assess the efficacy and safety of alternating bortezomib-dexamethasone (Bd) and lenalidomide-dexamethasone (Ld) (Bd/Ld) treatment in MM patients aged over 75 years (MARBLE trial). Patients received Bd therapy from days 1 to 35 and Ld therapy from days 36 to 63. For Bd therapy, patients were administered bortezomib 1.3 mg/m2 and oral dexamethasone 20 mg on days 1, 8, 15, and 22. For Ld therapy, they were administered lenalidomide 15 mg from days 36 to 56 and dexamethasone 10 mg on days 36, 43, 50, and 57. They underwent six treatment cycles in total, each consisting of a 63-day regimen. In total, 10 patients were enrolled, with a median age of 81 years. Efficacy was not evaluated because the patients were fewer than planned. The overall response rate was 80.0% and complete response rate 40.0%. Seventy percent of patients completed the study treatment. Progression-free survival and overall survival at 2 years were 40.0% and 80.0%, respectively. Adverse events of grade 3 or higher, including anemia, decreased lymphocyte count, neutropenia, and hypokalemia, were observed in eight patients. Alternating chemotherapy with Bd/Ld might be feasible, but its efficacy should be verified further.


Assuntos
Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento
18.
J Reprod Immunol ; 151: 103619, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35367871

RESUMO

Dexamethasone has been widely used in clinical practice to promote fetal lung maturity and reduce neonatal respiratory distress syndrome and perinatal mortality. Nevertheless, its administration is a double-edged sword, as a large number of studies have shown that there are obvious disadvantages in pregnant women and fetal development. In this review, we comprehensively retrospect the latest literature on the toxicological effects and mechanisms of dexamethasone on fetal development, in an attempt to provide a valuable basis for further studies and clinical trials in the future. Overall, prenatal dexamethasone exposure could lead to some adverse consequences on fetal organ systems through intrauterine programming based on the results of current animal and human researches. Potential sequelae include osteoarthritis, hypertension, fatty liver, glomerulosclerosis, depression, diabetes and infertility, some of which can pass on to the next generation. It must be noted that the evidence in humans is preliminary and limited by the small sample size. More studies in large-scale populations are needed to confirm if it raises the risk of sequelae in humans. In addition, we strongly support the application of dexamethasone as a pharmaceutical therapy in pregnant women with coronavirus disease 2019 before a better therapy is developed. However, the adverse side effects that may arise also cannot be ignored.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido , Animais , COVID-19/tratamento farmacológico , Dexametasona/efeitos adversos , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido , Gravidez
19.
Rinsho Ketsueki ; 63(2): 117-120, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35264502

RESUMO

An 88-year-old woman was diagnosed with multiple myeloma received third-line chemotherapy, including DBd (daratumumab [DARA], bortezomib, and dexamethasone [Dex]), and the myeloma was in remission. Sulfamethoxazole/trimethoprim (ST) prophylaxis was discontinued because the dose of Dex was reduced to 20 mg every 4 weeks after 21 cycles of DBd. After 28 cycles of DBd, altered consciousness with fever ensued, and she was referred to the emergency department where Listeria monocytogenes (LM) meningitis was diagnosed. CD38 inactivation is associated with increased LM susceptibility. In patients on Dara-based chemotherapy, antibiotic prophylaxis should be considered using ST, which has activity against Listeria.


Assuntos
Meningite por Listeria , Mieloma Múltiplo , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Feminino , Humanos , Meningite por Listeria/tratamento farmacológico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico
20.
BMC Infect Dis ; 22(1): 277, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35317729

RESUMO

BACKGROUND: Although the RECOVERY trial showed that dexamethasone was efficacious for the treatment of coronavirus disease 2019 (COVID-19), its impact on the risk of pulmonary embolism (PE) and other serious procoagulant events was not assessed. CASE PRESENTATION: Here we report the case of a previously healthy 83-year-old woman with COVID-19, without any genetic predisposition to thrombosis. She developed moderate respiratory distress 12 days after symptom onset and a 10-day course of dexamethasone therapy was initiated. Her clinical condition and imaging findings improved initially; however, they deteriorated after the completion of dexamethasone therapy, despite the improvement in her pneumonia and viral clearance. Laboratory tests showed markedly raised serum D-dimer, ferritin, and sIL-2R levels, and contrast-enhanced computed tomography showed deep vein thrombosis (DVT) in the left iliac vein and PE of the right pulmonary artery. The DVT and PE were successfully treated using intravenous heparin administration. CONCLUSIONS: This case illustrates the potential risk of rebound inflammation and procoagulant events following dexamethasone withdrawal. We believe that COVID-19-induced DVT and PE can be affected by dexamethasone therapy. Although dexamethasone reduces procoagulant factors, increases anticoagulant factors, and modulates cytokines, which can suppress/delay thrombus formation during treatment, it confers the risk for rebound cytokine production after treatment completion, triggering cytokine and coagulation cascades that can lead to thromboembolic diseases. In this critical clinical period, the patient's deteriorating condition may be overlooked because of the masking effects of dexamethasone treatment on fever and other clinical conditions and laboratory changes. Clinicians should follow-up coagulation markers carefully and contrast-enhanced computed tomography is useful for detecting coagulation; and, if PE occurs, therapeutic heparin administration is essential because emboli can also generate cytokines.


Assuntos
COVID-19 , Embolia Pulmonar , Trombose Venosa , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/tratamento farmacológico , Dexametasona/efeitos adversos , Feminino , Humanos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia
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