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BMJ Open Jun 2024Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and...
INTRODUCTION
Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.
METHODS AND ANALYSIS
This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.
ETHICS AND DISSEMINATION
This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.
TRIAL REGISTRATION NUMBER
jRCTs041210027.
Topics: Humans; Histiocytosis, Langerhans-Cell; Child; Adolescent; Japan; Adult; Dexamethasone; Young Adult; Zoledronic Acid; Male; Female; Clinical Trials, Phase II as Topic; Child, Preschool; Bone Density Conservation Agents
PubMed: 38910000
DOI: 10.1136/bmjopen-2024-084159 -
BMC Biotechnology Jun 2024Fungal diseases are often linked to poverty, which is associated with poor hygiene and sanitation conditions that have been severely worsened by the COVID-19 pandemic....
Fungal diseases are often linked to poverty, which is associated with poor hygiene and sanitation conditions that have been severely worsened by the COVID-19 pandemic. Moreover, COVID-19 patients are treated with Dexamethasone, a corticosteroid that promotes an immunosuppressive profile, making patients more susceptible to opportunistic fungal infections, such as those caused by Candida species. In this study, we analyzed the prevalence of Candida yeasts in wastewater samples collected to track viral genetic material during the COVID-19 pandemic and identified the yeasts using polyphasic taxonomy. Furthermore, we investigated the production of biofilm and hydrolytic enzymes, which are known virulence factors. Our findings revealed that all Candida species could form biofilms and exhibited moderate hydrolytic enzyme activity. We also proposed a workflow for monitoring wastewater using Colony PCR instead of conventional PCR, as this technique is fast, cost-effective, and reliable. This approach enhances the accurate taxonomic identification of yeasts in environmental samples, contributing to environmental monitoring as part of the One Health approach, which preconizes the monitoring of possible emergent pathogenic microorganisms, including fungi.
Topics: Wastewater; Brazil; Candida; COVID-19; Humans; Workflow; SARS-CoV-2; Biofilms; Environmental Monitoring; Pandemics
PubMed: 38909197
DOI: 10.1186/s12896-024-00868-z -
Pediatrics and Neonatology Jun 2024This study aimed to analyze the use of corticosteroids and epinephrine in neonates for the first extubation attempt and compared clinical characteristics of infants with...
BACKGROUND
This study aimed to analyze the use of corticosteroids and epinephrine in neonates for the first extubation attempt and compared clinical characteristics of infants with successful and failed extubation events.
METHODS
This was a retrospective cohort study conducted at a single level III neonatal intensive care unit in Taiwan. The study included 215 infants born between 2020 and 2021 who had been intubated for more than 48 h before their first extubation attempt. We compared perinatal and peri-extubation characteristics and outcomes between the two groups. Successful extubation was defined as freedom from invasive ventilatory support 72 h after extubation. The relationship between corticosteroids, local epinephrine, and successful extubation was determined using multivariate logistic regression analysis.
RESULTS
In the univariate analysis, the failed extubation group received a significantly higher proportion of intravenous dexamethasone (p = 0.006) than the successful extubation group. Furthermore, the failed extubation group had a longer duration of nebulized epinephrine (p = 0.034) and more episodes of local application of epinephrine to the superior larynx (p = 0.003) than the successful extubation group. Multivariate analysis revealed that the absence of lung atelectasis, tachycardia 72 h after extubation, and lower post-extubation PCO were the key factors associated with successful extubation.
CONCLUSIONS
There were trends toward systemic dexamethasone, local application of epinephrine to the superior larynx, and longer duration of nebulized epinephrine in the reintubation group. However, corticosteroid or local epinephrine use was not significantly associated with successful extubation. Lung atelectasis, elevated levels of carbon dioxide, and tachycardia were identified as risk factors for extubation failure.
PubMed: 38908947
DOI: 10.1016/j.pedneo.2023.12.010 -
Ear, Nose, & Throat Journal Jun 2024Evaluation of the effectiveness and posttreatment effects of intratympanic gentamicin and corticosteroids in treating patients with Ménière's disease (MD). Based on...
Evaluation of the effectiveness and posttreatment effects of intratympanic gentamicin and corticosteroids in treating patients with Ménière's disease (MD). Based on PubMed and Embase databases, randomized controlled trials using intratympanic injections of 4 drugs (gentamicin, methylprednisolone, dexamethasone, and placebo) for the treatment of MD were searched from 1995 to October 2023, and the literature was screened according to inclusion and exclusion criteria, and data were netted for meta-analysis using Stata 17. A total of 13 studies were selected, involving 559 participants, with follow-up time ranging from 3 to 28 months. Meta-analysis showed that there was no statistically significant difference in pure-tone average between gentamicin and dexamethasone [standardized mean difference (SMD) = 0.09, 95% confidence interval (CI) (-0.42, 0.24), < .05]. Compared to placebo, intratympanic injection of gentamicin [risk ratio (RR) = 1.18, 95% CI (0.43, 1.93)], methylprednisolone [RR = 0.88, 95% CI (0.07, 1.70)], and dexamethasone [RR = 0.70, 95% CI (-0.01, 1.41)] all showed better efficacy in treating vertigo. For the treatment of tinnitus, the SUCRA ranking results showed that dexamethasone was the most effective, followed by methylprednisolone and gentamicin. Pharmacological intervention is more effective than placebo in treating MD. Although gentamicin treatment shows significant effects in treating vertigo, corticosteroid combination therapy is markedly superior to gentamicin in controlling hearing loss and vertigo symptoms.
PubMed: 38907653
DOI: 10.1177/01455613241264421 -
Medicine Jun 2024Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH...
INTRODUCTION
Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection.
PATIENT CONCERNS
We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated.
DIAGNOSIS
The patient fulfilled diagnostic criteria for HLH.
INTERVENTIONS
Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed.
OUTCOMES
After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized.
LESSIONS
The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Child, Preschool; Otitis Media; Acute Disease; Dexamethasone; Cyclosporine; Etoposide; Immunoglobulins, Intravenous
PubMed: 38905364
DOI: 10.1097/MD.0000000000038616 -
Anesthesiology Jun 2024High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain...
BACKGROUND
High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. Our primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. Our secondary aim was to evaluate efficiency, value and impact of the novel trial design.
METHODS
This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across 7 hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone, 1 mg/kg, or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (>48 h), sepsis, renal failure, myocardial infarction, stroke and death.
RESULTS
Of 2093 patients assessed for eligibility, 1951 were randomized (median age 63 years, 80% male). The median number of home days was 23.0 (IQR, 20.1 to 24.1) in the dexamethasone group and 23.1 (IQR, 20.1 to 24.6) in the no dexamethasone group; median difference 0.1 (95% CI, -0.3 to 0.5), P=0.66. The rates of prolonged mechanical ventilation, RR 0.72 (95% CI, 0.48 to 1.08), sepsis, RR 1.02 (95% CI, 0.57 to 1.82), renal failure, RR 0.94 (95% CI, 0.80 to 1.12), myocardial infarction, RR 1.20 (95% CI, 0.30 to 4.82), stroke, RR 1.06 (95% CI, 0.54 to 2.08), and death, RR 0.72 (95% CI, 0.22 to 2.35), were comparable between groups (all P>0.10). Dexamethasone reduced intensive care unit stay, median 29 (IQR, 22 to 50) h vs. 43 (24 to 72) h, P=0.004. Our novel trial design was highly efficient (89.3% enrolment).
CONCLUSIONS
Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.
PubMed: 38904693
DOI: 10.1097/ALN.0000000000005127 -
International Journal of Medical... 2024Bone marrow-derived mesenchymal stem cells (MSCs), which are capable of differentiating into osteoblasts, are used in effective regenerative therapies. MSCs must be...
Bone marrow-derived mesenchymal stem cells (MSCs), which are capable of differentiating into osteoblasts, are used in effective regenerative therapies. MSCs must be prompted to differentiate into osteoblasts for MSC transplantation to be effective. In this study, osteoblast differentiation markers involved in bone formation were evaluated to investigate the stress resistance of bone marrow-derived rat MSCs to dexamethasone and hypoxia and their ability to differentiate into osteoblasts. MSCs were allowed to differentiate into osteoblasts for 21 days in three different environments (dexamethasone treatment, hypoxic conditions [1% oxygen], or both). Osteoblast differentiation potential was evaluated according to alkaline phosphatase levels and a mineralisation assay. Immunofluorescence staining was used to determine the protein expression of the osteoblast differentiation markers type I collagen and osteopontin. MSCs differentiated into osteoblasts under hypoxic conditions but differentiated more slowly upon treatment with dexamethasone and dexamethasone plus hypoxia relative to the control. MSCs preconditioned with dexamethasone or hypoxia and then allowed to differentiate into osteoblasts under similar conditions differentiated comparably to control MSCs. MSCs that developed resistance to dexamethasone or hypoxia differentiated more quickly into osteoblasts than those that did not. The findings suggest that increasing the resistance of MSCs to stress by preconditioning them via dexamethasone or hypoxia exposure could result in more rapid differentiation into osteoblasts following transplantation.
Topics: Dexamethasone; Mesenchymal Stem Cells; Animals; Osteoblasts; Cell Differentiation; Rats; Cell Hypoxia; Osteogenesis; Cells, Cultured; Alkaline Phosphatase; Humans; Mesenchymal Stem Cell Transplantation; Collagen Type I; Male
PubMed: 38903930
DOI: 10.7150/ijms.91222 -
Indian Journal of Anaesthesia Jun 2024Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the...
Olanzapine versus standard antiemetic prophylaxis for the prevention of post-discharge nausea and vomiting after propofol-based general anaesthesia: A randomised controlled trial.
BACKGROUND AND AIMS
Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the novel drug olanzapine, which has proved its efficiency in patients undergoing highly emetogenic chemotherapy for PDNV prevention.
METHODS
This randomised controlled trial recruited 106 adult patients (18-65 years) undergoing highly emetogenic daycare surgeries with propofol-based general anaesthesia (GA). Group O received preoperative oral olanzapine 10 mg, and Group C, acting as a control, received 8 mg of intravenous dexamethasone and 4 mg of ondansetron intraoperatively. The primary outcome was nausea (numeric rating scale >3) and/or vomiting 24 h after discharge. Secondary outcomes included nausea and vomiting in the post-anaesthesia care unit (PACU), severe nausea, vomiting and side effects. Normality was assessed using the Shapiro-Wilk test, and the independent samples -test or the Mann-Whitney test was used to compare continuous variables. Fisher's exact test was used to assess any non-random associations between the categorical variables.
RESULTS
The incidence and severity of postoperative nausea and vomiting were similar in both groups within PACU (four patients experienced nausea and vomiting, three had severe symptoms in Group O, = 0.057) and in the post-discharge period (three patients in Group O had nausea and vomiting compared to five patients in Group C, of which four were severe, = 0.484). The side effects (sedation, dizziness, and light-headedness) were comparable between the two groups.
CONCLUSION
A single preoperative oral olanzapine can be an effective alternative to standard antiemetic prophylaxis involving dexamethasone and ondansetron for preventing PDNV in highly emetogenic daycare surgeries with propofol-based GA.
PubMed: 38903258
DOI: 10.4103/ija.ija_1162_23 -
Indian Journal of Anaesthesia Jun 2024Postoperative neurocognitive dysfunction (PNCD) commonly occurs after surgery and prolongs hospital stays. Both direct noxious stimuli to the central nervous system and...
Effect of prophylactic corticosteroids on postoperative neurocognitive dysfunction in the adult population: An updated systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials.
BACKGROUND AND AIMS
Postoperative neurocognitive dysfunction (PNCD) commonly occurs after surgery and prolongs hospital stays. Both direct noxious stimuli to the central nervous system and systemic inflammation have been implicated. Due to their potent anti-inflammatory effects, corticosteroids have been utilised to attenuate the incidence and severity of PNCD. This systematic review and meta-analysis strived to evaluate the prophylactic role of perioperative corticosteroids for PNCD.
METHODS
A search was run in pre-defined databases for randomised controlled trials (RCTs) assessing the role of corticosteroids in preventing PNCD. The incidence of PNCD within 1 month was the primary outcome. Secondary outcomes included the use of antipsychotic medications for the treatment, postoperative infection, and hospital length of stay. The results are exhibited as odds ratio (OR) and the mean difference (MD) with 95% confidence interval (CI).
RESULTS
Fifteen RCTs comprising 15,398 patients were included. The incidence of PNCD was significantly lower in the corticosteroid group than in the control group, with a pooled OR of 0.75 (95% CI 0.58, 0.96; = 0.02; I = 66%). Trial sequential analysis showed the clinical benefit of corticosteroids in preventing PNCD; however, the requisite information size is still inadequate. The sub-group analysis supported the prophylactic effect of corticosteroids on delirium prevention but not on delayed neurocognitive recovery.
CONCLUSIONS
Our meta-analysis revealed statistically significant protective effects of corticosteroids on the incidence of PNCD. However, further studies are still needed to confirm the protective role of this commonly used and relatively safe strategy for preventing PNCD.
PubMed: 38903252
DOI: 10.4103/ija.ija_149_24 -
PharmacoEconomics - Open Jun 2024This study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple...
BACKGROUND AND OBJECTIVE
This study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple myeloma in Singapore: (1) daratumumab, lenalidomide, and dexamethasone and (2) bortezomib, lenalidomide, and dexamethasone. Additionally, it aimed to explore potential strategies to manage decision uncertainty and mitigate financial risk.
METHODS
A cost-effectiveness analysis from the healthcare system perspective was conducted using a partitioned survival model to estimate lifetime costs and quality-adjusted life years (QALYs) associated with daratumumab-based treatment and the bortezomib-based regimen. The analysis used data from the MAIA and SWOG S0777 trials and incorporated local real-world data where available. Sensitivity analyses were performed to evaluate the robustness of the findings, and a risk analysis was conducted to analyze various payer strategies in terms of their payer strategy and uncertainty burden (P-SUB), which account for the decision uncertainty and the additional cost of choosing a suboptimal intervention.
RESULTS
The incremental cost-effectiveness ratio (ICER) for daratumumab, lenalidomide, and dexamethasone (DRd) compared with bortezomib, lenalidomide, and dexamethasone (VRd) was US $90,364 per QALY gained. The results were sensitive to variations in survival for DRd, postprogression treatment costs, cost of hospice care, and hazard ratio for progression-free survival. The scenarios explored indicated that structural assumptions, such as the time horizon of the analysis, significantly influenced the results due to uncertainties arising from immature trial data and treatment efficacy over time. Among the various payer strategies compared, an upfront price discount for daratumumab emerged as the best approach with the lowest P-SUB at US $14,708.
CONCLUSION
In conclusion, this study finds that daratumumab as a first-line treatment for myeloma exceeds the cost-effectiveness threshold considered in this evaluation. An upfront price reduction is the recommended strategy to manage uncertainties and mitigate financial risks. These findings highlight the importance of targeted payer strategies to address specific types and sources of uncertainty.
PubMed: 38900407
DOI: 10.1007/s41669-024-00503-9