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Journal of Infection in Developing... Jul 2023The aim of this study was to demonstrate the purpose of adding antiviral (remdesivir) to the existing steroidal (dexamethasone) therapy in treating coronavirus disease... (Observational Study)
Observational Study
INTRODUCTION
The aim of this study was to demonstrate the purpose of adding antiviral (remdesivir) to the existing steroidal (dexamethasone) therapy in treating coronavirus disease 2019 (COVID-19).
METHODOLOGY
A retrospective observational case cohort study was carried out to compare the effect of dexamethasone alone and in combination with remdesivir in treating moderate and severe COVID-19 disease. The patients were divided into 2 groups: Group 1 included patients treated with dexamethasone alone, and Group 2 included patients treated with dexamethasone and remdesivir. Levels of inflammatory markers (C-reactive protein, D- dimer and lactate dehydrogenase), World Health Organization (WHO) ordinal scale scoring, symptomatic improvement in terms of fever, cough, shortness of breath, 6-minutes' walk test and SpO2 levels on day of admission (D0), 3 days and 5 days after admission (D3 and D5), and 10 days overall outcome (determined as death, or discharge with or without Long Term Oxygenation Therapy) were collected and analyzed.
RESULTS
Addition of remdesivir to dexamethasone in treating COVID 19 did not have any additional benefits. No additional role of remdesivir is seen in combating the disease except in case of 10 days outcome. However, the better 10-day outcome associated with the use of remdesivir was thought to be due to the patients who were on mechanical ventilation in the dexamethasone treated group at the time of inclusion.
CONCLUSIONS
Since a similar trend was seen in both groups, our study concluded no additional role of remdesivir in combating COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Retrospective Studies; Cohort Studies; COVID-19 Drug Treatment; Antiviral Agents; Dexamethasone
PubMed: 37515802
DOI: 10.3855/jidc.17971 -
Blood Advances Oct 2023Although randomized controlled trial data suggest that the more intensive triplet bortezomib-lenalidomide-dexamethasone (VRd) is superior to the less intensive doublet... (Randomized Controlled Trial)
Randomized Controlled Trial
Although randomized controlled trial data suggest that the more intensive triplet bortezomib-lenalidomide-dexamethasone (VRd) is superior to the less intensive doublet lenalidomide-dexamethasone (Rd) in patients newly diagnosed with multiple myeloma (MM), guidelines have historically recommended Rd over VRd for patients who are frail and may not tolerate a triplet. We identified 2573 patients (median age, 69.7 years) newly diagnosed with MM who were initiated on VRd (990) or Rd (1583) in the national US Veterans Affairs health care System from 2004 to 2020. We measured frailty using the Veterans Affairs Frailty Index. To reduce imbalance in confounding, we matched patients for MM stage and 1:1 based on a propensity score. Patients who were moderate-severely frail had a higher prevalence of stage III MM and myeloma-related frailty deficits than patients who were not frail. VRd vs Rd was associated with lower mortality (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94) in the overall matched population. Patients who were moderate-severely frail demonstrated the strongest association (HR 0.74; 95% CI, 0.56-0.97), whereas the association weakened in those who were mildly frail (HR, 0.80; 95% CI, 0.61-1.05) and nonfrail (HR, 0.86; 95% CI, 0.67-1.10). VRd vs Rd was associated with a modestly higher incidence of hospitalizations in the overall population, but this association weakened in patients who were moderate-severely frail. Our findings confirm the benefit of VRd over Rd in US veterans and further suggest that this benefit is strongest in patients with the highest levels of frailty, arguing that more intensive treatment of myeloma may be more effective treatment of frailty itself.
Topics: Humans; Aged; Multiple Myeloma; Lenalidomide; Frail Elderly; Frailty; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone
PubMed: 37582048
DOI: 10.1182/bloodadvances.2023011019 -
Effect of Preoperative Corticosteroids on Postoperative Glucose Control in Total Joint Arthroplasty.Arthroplasty Today Dec 2023Dexamethasone is a commonly used perioperative medication for the management of postoperative nausea and vomiting following total joint arthroplasty (TJA). However,...
BACKGROUND
Dexamethasone is a commonly used perioperative medication for the management of postoperative nausea and vomiting following total joint arthroplasty (TJA). However, concerns have been raised about its potential to cause hyperglycemia. This study aimed to investigate the impact of dexamethasone administration on glucose levels and complications in both diabetic and nondiabetic patients undergoing TJA.
METHODS
We performed a retrospective review of 1928 patients who underwent primary total knee and hip arthroplasty procedures at a large tertiary medical institution. Patients were divided into 2 groups based on whether they received preoperative dexamethasone. Postoperative blood glucose values and variability were measured, and data on complications were collected. We performed statistical analysis using descriptive analysis, multivariate logistic regression models, negative binomial regression, and a subset analysis to assess the impact of dexamethasone dose on postoperative glycemic control.
RESULTS
Preoperative dexamethasone did not significantly increase the mean glucose, fasting glucose, glucose variability, or 90-day complications in both the diabetic and nondiabetic groups. Nondiabetic patients who received dexamethasone had a significantly lower rate of intensive care unit admission ( < .01). Additionally, patients who received dexamethasone had a significantly shorter length of hospital stay compared to those who did not ( < .001).
CONCLUSIONS
Preoperative dexamethasone administration is a safe and effective method for preventing postoperative nausea and vomiting in patients undergoing TJA without significant adverse effects on glucose levels, glucose variability, or infection rates in both diabetics and nondiabetics. Preoperative dexamethasone decreases postoperative length of stay.
PubMed: 38077928
DOI: 10.1016/j.artd.2023.101238 -
Journal of Investigative Surgery : the... Dec 2023Glucocorticoids are widely used in clinical practice; however, they can cause side effects, such as osteoporosis. Acteoside (ACT) from Cistanche has been used to combat...
OBJECTIVE
Glucocorticoids are widely used in clinical practice; however, they can cause side effects, such as osteoporosis. Acteoside (ACT) from Cistanche has been used to combat a variety of diseases. The study was conducted to evaluate the efficacy of ACT in glucocorticoid-induced osteoporosis (GIOP) and its potential mechanism.
METHODS
Dexamethasone (Dex) was injected intramuscularly to induce osteoporosis in a rat model, and ACT was given orally. ACT was supplemented in Dex-stimulated osteoblastic MC3T3-E1 cells. RT-qPCR was performed to assess the mRNA levels of bone formation (Runx2, CoL1A1), and bone resorption (OPG and RANKL). A commercial ELISA kit was applied to assess serum OC and CTX levels. Western blot was performed to assess protein levels in the PI3K/AKT/mTOR signaling pathway. CCK-8 assay and flow cytometry were performed to assess osteoblast viability and apoptosis.
RESULTS
ACT reduced Dex-induced bone microstructure deterioration, increased serum levels of OC, and decreased the levels of CTX ( < 0.05). In the MC3T3-E1 cells, Dex inhibited cell viability and promoted apoptosis; however, this effect was greatly attenuated by ACT ( < 0.05). Concurrently, ACT reversed the reduction in Runx2, osterix, CoL1A1, and OPG mRNA levels, ALP activity, and the promotion of RANKL by Dex. Additionally, ACT attenuated Dex-induced inhibition of p-AKT/AKT, p-mTOR/mTOR, and p-PI3K/PI3K protein levels by Dex ( < 0.05), while the PI3K/AKT/mTOR pathway inhibitor LY294002 diminished the potential effect of ACT ( < 0.05).
CONCLUSION
ACT from Cistanche may exert osteoprotective effects by activating the PI3K/AKT/mTOR signaling pathway to alleviate Dex-induced osteoporosis.
Topics: Rats; Animals; Glucocorticoids; Core Binding Factor Alpha 1 Subunit; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Cistanche; Dexamethasone; Osteoporosis; Osteoblasts; TOR Serine-Threonine Kinases; RNA, Messenger
PubMed: 36521840
DOI: 10.1080/08941939.2022.2154578 -
Journal of Cellular and Molecular... Dec 2023Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast...
Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC-induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low-dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)-treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex-induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex-induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.
Topics: Rats; Animals; Dexamethasone; NF-E2-Related Factor 2; Osteogenesis; Glucocorticoids; Oxidative Stress; Acetophenones; Apoptosis; Osteoblasts; Mitochondrial Diseases
PubMed: 37749949
DOI: 10.1111/jcmm.17974 -
Annals of Hematology Mar 2024This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus...
This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.
Topics: Humans; Adult; Middle Aged; Aged; Multiple Myeloma; Dexamethasone; Neoplasm Recurrence, Local; Antineoplastic Combined Chemotherapy Protocols; Thalidomide
PubMed: 38112795
DOI: 10.1007/s00277-023-05558-y -
Frontiers in Immunology 2024Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied....
BACKGROUND
Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.
METHODS
High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses.
RESULTS
Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells.
CONCLUSION
High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.
Topics: Humans; Glioblastoma; Leukocytes, Mononuclear; CD4-Positive T-Lymphocytes; Immunotherapy; Dexamethasone
PubMed: 38318180
DOI: 10.3389/fimmu.2024.1343484 -
Haematologica Nov 2023To improve the outcomes of patients with the otherwise incurable hematologic malignancy of multiple myeloma (MM), a key paradigm includes initial treatment to establish...
To improve the outcomes of patients with the otherwise incurable hematologic malignancy of multiple myeloma (MM), a key paradigm includes initial treatment to establish disease control rapidly followed by maintenance therapy to ensure durability of response with manageable toxicity. However, patients' prognosis worsens after relapse, and the disease burden and drug toxicities are generally more challenging with subsequent lines of therapy. It is therefore particularly important that patients with newly diagnosed multiple myeloma (NDMM) receive optimal frontline therapy. The combination of lenalidomide, bortezomib, and dexamethasone (RVd) has consistently demonstrated a tolerable safety profile with significant and clinically relevant benefit, including deep and durable responses with improved survival in patients with NDMM regardless of their transplant eligibility. Furthermore, comparative studies evaluating this triplet regimen against both doublet and other triplet regimens have established RVd as a standard of care in this setting based upon its remarkable and concordant efficacy. Given the breadth of clinical data, physician familiarity, inclusion in treatment guidelines, and the emerging potential of RVd-containing quadruplet regimens, RVd will likely continue as a key cornerstone of the treatment of NDMM, and its role will therefore likely continue to grow as a therapeutic backbone in the initial treatment of MM.
Topics: Humans; Multiple Myeloma; Bortezomib; Lenalidomide; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local
PubMed: 37608773
DOI: 10.3324/haematol.2022.282624 -
PloS One 2023Cyasterone alleviated the apoptosis of BMSCs induced by Dexamethasone via the PI3K/AKT signaling pathway. In addition, Cyasterone had a protective effect on SIONFH model...
CONTEXT
Cyasterone alleviated the apoptosis of BMSCs induced by Dexamethasone via the PI3K/AKT signaling pathway. In addition, Cyasterone had a protective effect on SIONFH model rats by reducing the percentage of empty bone lacunae.
OBJECTIVE
To study the effect of Cyasterone on apoptosis of rat BMSCs and its function on the SIONFH rat model.
METHODS
Rat BMSCs were cultured and divided into Control, DXM and Cyasterone (DXM+Cyasterone) groups. The apoptosis of each group was detected by flow cytometry, the expressions of Caspase-3 and Caspase-9 were detected by immunofluorescence staining, and the mRNA and protein expressions of AKT, BAX, P53, P85, Bcl-2 and Cytochrome C were detected by qPCR and WB. In animal experiments, the femoral head of rats were subjected to HE staining and Micro-CT to observe the necrosis and repair conditions.
RESULTS
The apoptosis rate of DXM and Cyasterone groups increased compared with Control group, and the apoptosis rate of Cyasterone group decreased compared with DXM group. Compared with DXM group, the mRNA expression of BAX, P53, P85 and Cytochrome C in Cyasterone group were increased, while the protein expression of AKT and Bcl-2 decreased. The histopathological and morphological analysis showed that Cyasterone promoted the trabecular bone structure in rat, which evenly benefit for the repair of SIONFH.
CONCLUSION
Cyasterone can reduce the apoptosis of rat BMSCs induced by Dexamethasone, and help promoting the bone repair in SIONFH rats.
Topics: Rats; Animals; Proto-Oncogene Proteins c-akt; bcl-2-Associated X Protein; Femur Head; Cytochromes c; Phosphatidylinositol 3-Kinases; Tumor Suppressor Protein p53; Osteonecrosis; Proto-Oncogene Proteins c-bcl-2; Steroids; Apoptosis; Dexamethasone; RNA, Messenger
PubMed: 37903142
DOI: 10.1371/journal.pone.0293530 -
Annals of Saudi Medicine 2023Rebound pain is characterized by sudden, significant acute postoperative pain occurring after the resolution of inter-scalene block (ISB); it affects the quality of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Rebound pain is characterized by sudden, significant acute postoperative pain occurring after the resolution of inter-scalene block (ISB); it affects the quality of recovery postoperatively. Dexamethasone increases ISB resolution time and decreases opioid consumption and the incidence of rebound pain.
OBJECTIVE
Evaluate whether multimodal analgesia including intravenous dexamethasone administration with preoperative ISB reduces the incidence of rebound pain.
DESIGN
Prospective, randomized, controlled trial.
SETTING
Tertiary university hospital.
SAMPLE SIZE
60 patients.
PATIENTS AND METHODS
Patients who underwent shoulder surgery under general anesthesia were assigned randomly to two different multimodal analgesia protocols. Thirty patients received 5 mg IV dexamethasone with non-steroid, paracetamol, and ISB with 15 mL 0.5% bupivacaine, while the control patients received the same regimen and ISB with 15 mL 0.5% bupivacaine without dexamethasone. Postoperative opioids were given to any patient on demand.
MAIN OUTCOMES MEASURES
Effect of IV dexamethasone on pain score and incidence of rebound pain after ISB resolution and postoperative opioid consumption at 0-48 hours, numerical pain rating scale (NPRS) scores, sleep scale scores, and quality of recovery-15 scores (QoR-15).
RESULTS
The incidence of rebound pain was lower in the dexamethasone group than in the control group (73.3% and 30%, respectively, =.001). NPRS scores after ISB resolution were lower in the dexamethasone group (5 ([4-7]), 8 ([5.75-8]), <.001, respectively). Those who received IV dexamethasone had less sleep disturbances (<.001) and higher QoR-15 on day 1 (<.001) and day 7 (=.020) postoperatively.
CONCLUSIONS
IV dexamethasone added to the ISB block resulted in a lower incidence of rebound pain. In addition, better results were obtained in postoperative sleep quality and QoR-15.
LIMITATIONS
Single-center study.
Topics: Humans; Brachial Plexus Block; Shoulder; Analgesics, Opioid; Prospective Studies; Bupivacaine; Pain, Postoperative; Analgesia; Dexamethasone; Anesthetics, Local; Arthroscopy
PubMed: 38071444
DOI: 10.5144/0256-4947.2023.339