Solid Lipid Nanoparticles Loaded with Dexamethasone Palmitate for Pulmonary Inflammation Treatment by Nebulization Approach.

Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations.

Hot-Melt Extrusion-Based Dexamethasone-PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation.

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products.

Comparative Efficacy of Inhaled and Intravenous Corticosteroids in Managing COVID-19-Related Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs fail to provide sufficient oxygen to the body's vital organs. It is commonly associated with COVID-19 patients. Severe cases of COVID-19 can lead to lung damage and organ failure due to an immune response in the body. To mitigate these effects, corticosteroids, which are known for their anti-inflammatory properties, have been suggested as a potential treatment option. The primary focus of this study was to assess the impact of various corticosteroid administration methods on the outcomes of patients with COVID-19. Methods: The current study was conducted on COVID-19 patients divided into three groups. The first group was administered 6 mg of intravenous (IV) dexamethasone; the second group received 1 mg/kg of IV methylprednisolone (methylprednisolone); and the third group received budesonide respirable solution at a dosage of 1mg twice daily. The neubilizer used was a vibrating mesh nebulizer (VMN). All patients received standard care. We found that dexamethasone administered intravenously led to a significant reduction in C-reactive protein levels, surpassing the effectiveness of both IV methylprednisolone and inhaled budesonide. Oxygen saturation without mask change over time showed statistically significant differences (p = 0.004) in favor of the budesonide and dexamethasone groups for all days. Individuals who received methylprednisolone showed a significant decrease in mortality rate and an extended survival duration, with statistical significance observed at p = 0.024. The rest of the parameters, including ferritin, lymphocytes, total leukocyte count, platelets, hemoglobin, urea, serum potassium, serum sodium, serum creatinine, serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase, uric acid, albumin, globulin, erythrocyte sedimentation rate, international normalized ratio, oxygen saturation with flow, and oxygen flow, showed no statistically significant differences between the three drugs. In conclusion, treatment with IV methylprednisolone (1 mg/kg) resulted in a shorter hospital stay, decreased reliance on ventilation, and improved health outcomes for COVID-19 patients compared to using dexamethasone at a daily dosage of 6 mg or budesonide respirable solution at a dosage of 1mg twice daily.

Perianeurysmal vasogenic oedema (PAVO): A single centre 10-year retrospective review.

INTRODUCTION: Perianeurysmal Vasogenic Oedema (PAVO) is a rare but important complication of endovascular treatment of intracranial aneurysms. Many potential risk factors have been identified including age, aneurysm size, aneurysm location, immunological profile, type of coil used, diabetes, hypertension, and smoking. PAVO can cause persistent post-procedural symptoms, subsequently increasing post-embolization morbidity. METHODS: A 10-year retrospective review was conducted between 2011 and 2021 at Royal Preston Hospital, Preston, UK. RESULTS: We identified 8 patients that fit our inclusion criteria. This included 6 (75%) females and 2 (25%) males. The mean age was 64. All patients had anterior circulation aneurysms with the middle cerebral artery (MCA) being the most common site. The mean aneurysm size was 12 mm. Our patients were managed with a range of endovascular techniques. One patient had pre-treatment PAVO while 7 patients had post-embolization PAVO. Five patients were symptomatic, and 3 cases were asymptomatic with only radiological evidence of PAVO. Five patients were managed with varying courses of dexamethasone. PAVO resolution was achieved in 4 cases. The oedema significantly improved in 3 cases, but transiently progressed in 1 case. CONCLUSIONS: PAVO is a rare but important complication of endovascular management of intracranial aneurysms. We have shown that patients can be effectively managed with steroids with resultant oedema regression and symptomatic improvement. Many risk factors have been associated with PAVO, but further research is needed to better understand their role in PAVO development and help develop other therapeutic options.

Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury.

Acute kidney injury (AKI) increases the risk of in-hospital death, adds to expense of care, and risk of early chronic kidney disease. AKI often follows an acute event such that timely treatment could ameliorate AKI and potentially reduce the risk of additional disease. Despite therapeutic success of dexamethasone in animal models, clinical trials have not demonstrated broad success. To improve the safety and efficacy of dexamethasone for AKI, we developed and characterized a novel, kidney-specific nanoparticle enabling specific within-kidney targeting to proximal tubular epithelial cells provided by the megalin ligand cilastatin. Cilastatin and dexamethasone were complexed to H-Dot nanoparticles, which were constructed from generally recognized as safe components. Cilastatin/Dexamethasone/H-Dot nanotherapeutics were found to be stable at plasma pH and demonstrated salutary release kinetics at urine pH. In vivo, they were specifically biodistributed to the kidney and bladder, with 75% recovery in the urine and with reduced systemic toxicity compared to native dexamethasone. Cilastatin complexation conferred proximal tubular epithelial cell specificity within the kidney in vivo, and enabled dexamethasone delivery to the proximal tubular epithelial cell nucleus in vitro. The Cilastatin/Dexamethasone/H-Dot nanotherapeutic improved kidney function and reduced kidney cellular injury when administered to male C57BL/6 mice in two translational models of AKI (rhabdomyolysis and bilateral ischemia reperfusion). Thus, our design-based targeting and therapeutic loading of a kidney-specific nanoparticle resulted in preservation of the efficacy of dexamethasone, combined with reduced off-target disposition and toxic effects. Hence, our study illustrates a potential strategy to target AKI and other diseases of the kidney.

Efficacy of Switching From Oral to Intravenous Administration for Dexamethasone-Induced Hiccups in CyberKnife Radiotherapy: A Case Report.

Steroids are commonly used for medical purposes. While hiccups are a recognized side effect of steroid therapy, we have not found any reports of hiccups interfering with the progress of radiotherapy. A case of dexamethasone (DEX)-induced hiccups (DIH) during CyberKnife radiotherapy (CKR) is presented. A 42-year-old man with neurofibromatosis type I had a history of malignant peripheral schwannomas originating in the right femur. We started to perform CKR with oral DEX at an increased dose of 4 mg/day for the recurrence of cranial metastasis and primary lesions. Severe hiccups developed four days after the increased DEX dose. DEX was stopped six days after CKR initiation, and the hiccups subsided over the next four days. However, the CKR procedure was not possible due to the patient's worsening swelling of the head and thigh lesions, which prevented the proper fit of the mesh face mask and body fixation device. Intravenous (IV) DEX 6.6 mg/day was initiated, which allowed the resumption of CKR due to reduced swelling of the lesions. The CKR was completed due to the absence of hiccups following the transition to IV DEX. DIH could occur even at a dosage of 4 mg/day when taken orally. Our case suggests the significance of recognizing DIH during radiotherapy. Switching the administration from oral to IV DEX may be an option for dealing with DIH.

Transversus Abdominis Plane Block Following Cesarean Section: A Prospective Randomized Controlled Study Comparing the Effects on Pain Levels of Bupivacaine, Bupivacaine + Dexmedetomidine, and Bupivacaine + Dexamethasone.

Background: The transversus abdominis plane (TAP) block is providing effective postoperative analgesia in patients undergoing cesarean section (CS). This study aims to evaluate and compare the effects on pain levels of bupivacaine alone versus bupivacaine combined with dexmedetomidine and bupivacaine combined with dexamethasone in ultrasound-guided TAP block for postoperative pain after CS. Material and Method: In this randomized controlled trial, 120 patients with American Society of Anesthesiologists (ASA) physical status I and II scheduled for elective cesarean section under spinal anesthesia were randomly divided into three groups. At the end of the surgery, an ultrasound-guided TAP block was performed on all patients: bupivacaine 0.5% (Group B), bupivacaine 0.5% + dexmedetomidine (1 µg/kg) (Group BD), and bupivacaine 0.5% + dexamethasone (4 mg) (Group BDx). Postoperatively, all patients were evaluated at 0, 1, 4, 8, 16, and 24 h for visual analog scores VASs, tramadol consumption, complications, and patient satisfaction. A p value of < 0.05 is statistically significant. Results: At 0 h, VASs in the sitting and supine positions were significantly higher in the BDx group (0.85 ± 1.61 and 0.85 ± 1.36, respectively) compared to the B group (0.05 ± 0.32 in both positions) and the BD group (0.15 ± 0.48 in both positions) (p = 0.005 and p = 0.001, respectively). At the 24th hour, VASs in the sitting and supine positions were significantly lower in the BDx group (1.7 ± 1.2 and 1.43 ± 1.05) compared to the B group (2.3 ± 0.68 and 2.2 ± 0.72) and the BD group (2.57 ± 1.01 and 2.28 ± 0.78) (p = 0.005 and p = 0.001, respectively). At 0 h, the tramadol requirement was highest in the BDx group at 12.5%, while it was not required in the B and BD groups (p = 0.005). At 0 h, the rate of nausea and vomiting was highest in the BDx group at 17.5%, compared to 2.5% in the BD group and 0% in the B group (p = 0.003). Patient satisfaction scores were higher in the dexamethasone group compared to the other groups. This was significant between Group B and Group BDx (p = 0.009 < 0.05). Conclusions: Adding dexmedetomidine or dexamethasone to bupivacaine in ultrasound-guided TAP blocks reduces postoperative pain and increases patient satisfaction after cesarean sections. Dexamethasone, due to its delayed onset but extended duration, achieves lower pain scores and higher satisfaction. Further research is necessary to confirm these findings.

Intravitreal Injection of Conbercept Combined with Dexamethasone for Macular Edema Following Central Retinal Vein Occlusion.

Background: To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO). Methods: This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 µm at month 12. Results: 33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 (t = 4.221, P = 0.000; and t = 4.834, P = 0.000) with no significant difference between the two groups (t = 0.071, P = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 µm (t = 8.261, P = 0.000) compared to 431.36 ± 294.55 (t = 8.413, P = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups (t = 0.053, P = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred. Conclusion: Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group. Trial Registration: The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).

Intrathecal dexamethasone-bupivacaine combination with bupivacaine alone in spinal anesthesia for cesarean delivery.

Background: Postoperative pain management can be achieved by adjuvant medications during the analgesia procedure. The study investigated the effect of intrathecal dexamethasone-bupivacaine combination with bupivacaine alone in spinal anesthesia for cesarean delivery. Methods: This randomized, double-blind clinical examination included 50 females who had previously experienced a cesarean section. The participants were assigned randomly into two categories: the intervention group, received intrathecal bupivacaine-dexamethasone, and the control group, received intrathecal bupivacaine-normal saline. Levels of pain were evaluated using a 10 cm visual analog scale (VAS) at intervals of 30 minutes, 1 hour, 2 hours after the operation. The span of the sensory block and postoperative analgesia were assessed. Results: The inclusion of intrathecal dexamethasone with bupivacaine resulted in a significant enhancement in the duration of pain relief during the intervention, lasting for an average of 473.4 ± 39.95 minutes (p<0.001). The duration of sensory and motor block analgesia in the intervention group was more than the control group (128.32 ± 7.30 vs. 92.84 ± 7.84) and (155.6±12.34 vs. 126.16±11.89), respectively (p<0.001). Pain score on the VAS scale at 30, 60, and 120 minutes was significantly lower in the intervention group (p<0.001). There was no difference in side effects and onset time between the study groups. Conclusion: The inclusion of intrathecal dexamethasone alongside bupivacaine has demonstrated enhancement in the duration of sensory block during spinal anesthesia. This improvement was observed without any alterations in the time it takes for the anesthesia to take effect and without any adverse effects during the postoperative period.

The development of a dexamethasone challenge model for evaluating feed additives in sheep.

OBJECTIVE: To develop an accessible ruminant immune challenge model for rapid in vivo assessments of feed additives. ANIMALS: 60 hair-breed ram lambs. METHODS: Sheep were randomly assigned to 1 of 4 treatments: treatment 1, not immunosuppressed, control fed (n = 12); treatment 2, immunosuppressed, supplemented with a yeast and botanical extract (n = 18); treatment 3, immunosuppressed, supplemented with a blend of natural aluminosilicates and yeast components (n = 18); and treatment 4, immunosuppressed, control fed (n = 12). Twice-daily injections of dexamethasone (Dex; 0.1 mg/kg bodyweight, SC) were used to induce immunosuppression throughout the study (from September 25, 2020, to November 2, 2020). All sheep were immunized with keyhole limpet hemocyanin (KLH) on days 0 and 14 and injected with heat-aggregated KLH, ID, to induce a skin induration on day 15. Measurements included body weight (BW), average daily gain (ADG), CBC, and skin induration diameter. RESULTS: Dex treatment resulted in reduced BW and ADG that was not mitigated by either feed additive. Dex reduced lymphocyte percentage, RBC count, hemoglobin, hematocrit, and skin induration diameter and increased concentrations of granulocytes and granulocyte percentage. Effects on hematocrit, hemoglobin, RBC, and skin induration diameter were mitigated with the addition of feed additives. CLINICAL RELEVANCE: The described model is a tool to evaluate the ability of feed additives to mitigate the immunosuppressive effects of Dex.

Apigenin attenuates serum concentrations of TNF-a, interleukin 1b and interleukin 6 in lipopolysaccharide-stimulated rats.

Objective: The use of flavonoids is increasing due to their cost-effectiveness and less adverse reaction. Therefore, the effect of apigenin on lipopolysaccharide (LPS)-induced inflammation was investigated by measuring IL-1b, IL-6, and TNF-a, of serum in the male rats. Materials and Methods: Ninety male wistar rats were divided in 6 groups included; control, sham, dexamethasone 15 mg/kg, intraperitoneally (i.p.), and apigenin (5, 15, and 30 mg/kg, i.p). Thirty minutes after the administration of solvent or apigenin, LPS (30 µg/kg, i.p) was injected. At time intervals of 4, 12 and 24 hr after injection, blood samples were taken and the concentrations of TNF-a, IL-1b and IL-6 were measured by enzyme-linked immunosorbent assay. Results: Compared to the control, apigenin (5 mg/kg) decreased the level of TNF-a, and IL-1b in a period of 24 hr (p<0.05). The concentration of IL-6 decreased significantly by apigenin (15 mg/kg) 24 hr after injection (p<0.05). Apigenin (30 mg/kg) decreased the level of TNF-a, at all three time points (4 hr; p<0.05, 12 hr; p<0.01, and 24 hr; p<0.01), and the level of IL-1b (p<0.01), 24 hr and the level of IL-6 at 4 hr (p<0.05), and 24 hr (p<0.01) after LPS injection. Conclusion: Apigenin can suppress serum inflammatory cytokines, similar to dexamethasone.

Combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane block for postoperative analgesia in gastric cancer patients: A double-blinded randomized controlled trial.

STUDY OBJECTIVE: We conducted this double-blinded randomized controlled trial to examine whether the combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane (TAP) block could improve analgesia efficacy and duration for gastric cancer patients. DESIGN: Randomized controlled trial. SETTING: The preoperative area, operating room, postanesthesia recovery room and bed ward. PATIENTS: A total of 312 adult patients (104 per group) with gastric cancer were included. INTERVENTIONS: Patients received bilateral subcostal TAP block with three different anesthetics (60 ml 0.25% ropivacaine added with 10 mg dexamethasone and 1 µg·kg-1 dexmedetomidine [A] or 10 mg dexamethasone [B] or 1 µg·kg-1 dexmedetomidine [C]). MEASUREMENTS: The primary outcome was the incidence of moderate-to-severe pain 24 h on movement. Secondary outcomes included incidence of moderate-to-severe pain, pain score, opioids use, recovery quality and adverse events. MAIN RESULTS: The incidence of moderate-to-severe pain on movement 24 h postoperatively of group A was significantly lower than group B (45.19% vs 63.46%; RR 0.71; 95% CI, 0.55 to 0.92) and group C (45.19% vs 73.08%, RR 0.62; 95% CI, 0.49 to 0.79). The median moving pain scores decreased significantly at 24 h (3.00 [3.00,5.00] vs 4.00 [3.00,6.00] vs 4.00 [3.00,5.00]; P < 0.001). There were significant differences in the opioids consumption within the first 24 h (27.5 [17.0,37.2] vs 30.0 [20.0,42.0] vs 32.0 [25.0,44.0] mg; P = 0.01) and the duration to first rescue analgesia (65.5 ± 26.7 vs 45.9 ± 34.5 vs 49.2 ± 27.2 h; P = 0.04). CONCLUSIONS: The combination with dexamethasone and dexmedetomidine as adjuvants for TAP block reduced the incidence of moderate-to-severe pain and pain score both on movement and at rest at 24 h with prolonged duration to first rescue analgesia after gastric cancer surgery. TRIAL REGISTRATION NUMBER: ChiCTR2000037981.

Hydroxypropyl Cellulose-Based Orally Dissolving Film Loaded with Insoluble Dexamethasone for Treatment of Oral Ulcers.

Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.

Lenalidomide and dexamethasone for Rosai-Dorfman disease: a single arm, single center, prospective phase 2 study.

Background: Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. Methods: This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023 at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25 mg days 1-21 plus dexamethasone 40 mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p < 0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). Findings: The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n = 9) and 70% (n = 16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n = 7) complete remission, 57% (n = 13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p = 0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p = 0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n = 12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n = 2, 9%), glucose intolerance (n = 2, 9%), edema (n = 2, 9%), insomnia (n = 1, 4%), and tremor (n = 1, 4%). Interpretation: Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. Funding: National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.

Efficacy of sarilumab and dexamethasone co-administration for lowering multiple blood biomarkers in the treatment of cytokine release syndrome in hospitalized COVID-19 patients.

The current study was planned to explore the potential synergistic role of the co-administration of sarilumab and dexamethasone in reducing blood biomarkers associated with cytokine release syndrome in hospitalised patients of coronavirus disease-2019. The sample comprised 22 patients hospitalised with severe and critical severity levels and who were treated with sarilumab and dexamethasone. Positive responses were seen in blood biomarkers, including decreased interleukin-6 alpha levels and improved oxygen saturation. Tumour necrosis factor, Ddimer, C-reactive protein, ferritin and lymphocyte count also showed positive responses in patients who survived than those who died. Lactate dehydrogenase levels fluctuated with improvement among the survivors, but had limited effectiveness in those who died. The findings suggested promising avenues for future treatment strategies in patients with severe coronavirus disease-2019 and cytokine release syndrome.

Vascular responsiveness to low-dose dexamethasone in extremely premature infants: Negative influence of fetal growth restriction.

Dexamethasone is frequently prescribed for preterm infants to wean from respiratory support and/or to facilitate extubation. This pre-post intervention prospective study ascertained the impact on clinical (respiratory support) and echocardiographic parameters after dexamethasone therapy in preterm FGR infants compared to AGA infants. Echocardiography was performed within 24 hours before the start and after completion of 10-day therapy. Parameters assessed included those reflecting pulmonary vascular resistance and right ventricular output. Seventeen FGR infants (birth gestation and birthweight 25.2±1.1 weeks and 497±92g) were compared with 22 AGA infants (gestation and birthweight 24.5±0.8 and 663±100g). Baseline respiratory severity score (mean airway pressure x fractional inspired oxygen) was comparable between the groups, (median [interquartile range] FGR: 10 [6, 13] vs AGA: 8±2.8, P=0.08). Pre-dexamethasone parameters of pulmonary vascular resistance (FGR: 0.19±0.03 vs AGA 0.2±0.03, P=0.16) and right ventricular output (FGR: 171±20 vs 174±17 ml/kg/min, P=0.6) were statistically comparable. At post-dexamethasone assessments, the decrease in respiratory severity score was significantly greater in AGA infants, (median [interquartile range] FGR: 10 [6, 13] to 9 [2.6, 13.5], P=0.009 vs AGA: 8±2.8 to 3±1, P<0.0001). Improvement in measures of pulmonary vascular resistance (time to peak velocity/right ventricular ejection time) was greater in AGA infants (FGR: 0.19±0.03 to 0.2±0.03, P=0.13 vs AGA 0.2±0.03 to 0.25±0.03, P<0.0001). The improvement in right ventricular output was significantly greater in AGA infants (171±20 to 190±21, P=0.014 vs 174±17 to 203±22, P<0.0001). This highlights differential cardiorespiratory responsiveness to dexamethasone in extremely preterm FGR infants, which may reflect the in-utero maladaptive state.

Predictors and outcomes of extubation failures in a pediatric intensive care unit: A retrospective study.

Objectives: This study was aimed at determining the extubation failure (EF) rate in a pediatric intensive care unit (PICU), and assessing the etiology, associated risk factors, and outcomes. Methods: We conducted a retrospective study on 335 pediatric patients admitted to King Abdulaziz University Hospital between 2018 and 2020, ranging in age from 1 month to 14 years, who required invasive mechanical ventilation (MV) for >24 h. Extubation readiness was determined by the attending pediatric intensive care physician, according to the patients' clinical status and extubation readiness criteria. Results: In the cohort of 335 patients, 42 experienced issues during extubation (failure rate, 12.5%). Cardiovascular disease (42.9%) was the main primary admission condition in patients with EF. Younger age (median, interquartile range [IQR]: 4, 1.38-36 months) was strongly associated with EF compared with successful extubation (median, IQR: 12, 2-48; p = 0.036), and with a high predicted mortality rate (10.9%; p < 0.001) and Pediatric Risk of Mortality III (PRISM) score (13; p < 0.001). Furthermore, prolonged ICU stay (25.5 days; p < 0.001) and longer MV requirements (4 days; p < 0.001) before extubation in patients with EF were associated with a high mortality rate (∼12%; p < 0.001). Interestingly, dexamethasone administration before extubation significantly alleviated EF risk (28.3%; p < 0.001). Conclusion: A higher EF rate in younger patients may potentially be associated with longer ICU stays, prolonged MV requirements before extubation, and the primary diagnostic condition. Dexamethasone effectively alleviated EF incidence. Further research with a rigorous evidence-based study design is necessary to substantiate the factors identified as predictors of EF and to develop strategies to avoid EF.

Effectiveness of Adding Dexamethasone to Lidocaine in Upper Limbs Nerve Blocks: A Systematic Review.

PURPOSE: The use of perineural dexamethasone as an adjuvant drug to peripheral nerve block for postoperative pain is controversial. This systematic review aimed to determine the effectiveness of adding dexamethasone to lidocaine in upper limb nerve blocks. DESIGN: Systematic review. METHODS: This review used a comprehensive search strategy to retrieve relevant published randomized trial articles that fulfilled the inclusion and exclusion criteria, without time limits, (until December 2023) that assessed the effects of a combination of dexamethasone to lidocaine in upper limb nerve blocks. The databases used for the electronic literature search included PubMed, Embase, and Clinical Trials.gov, dbGaP, Cochrane library, and Google Scholar. There was no language, gender, or age limitation. This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. FINDINGS: Of 3,926 articles identified by the initial search, 8 studies that met our inclusion criteria. All articles were original research studies. All eight articles were clinical trials. The sample size in the selected studies ranged from 30 to 90 people. Studies demonstrated that combining dexamethasone with lidocaine significantly improved the quality of peripheral nerve blocks, increased the analgesia period, and decreased analgesic consumption. CONCLUSIONS: This review supported that the combination of dexamethasone (dose of 4 to 10 mg) and lidocaine (concentration of 1.5% to 2%) for upper limb block was more effective and beneficial without any side effects. However, further clinical trials in this regard with more data, various regions, and larger sample sizes to support our hypothesis are recommended.

Incidence of Fatigue Following Dexamethasone Administration for Supportive Therapy and Efficacy of Tapering in Perioperative Chemotherapy for Breast Cancer: A Retrospective Observational Study.

In perioperative chemotherapy for breast cancer, dexamethasone (DEX) is administered at high dose to prevent adverse effects. Abrupt cessation of high-dose DEX treatment induces fatigue, but the incidence of the fatigue is uncertain. In this study, we retrospectively evaluated the incidence of fatigue following DEX administration for supportive therapy and the improvement of fatigue with DEX tapering, a gradual reduction of the daily dose, in breast cancer patients. The subjects were 124 patients with breast cancer receiving epirubicin- or docetaxel-based regimens as perioperative chemotherapy. Of all patients, 16.1% of patients experienced fatigue after cessation of DEX administration. The severity of fatigue was grade 1 in 6.5% of patients, grade 2 in 8.1% of patients, and grade 3 in 1.6% of patients. There were no significant differences in dose and duration of DEX administration between the group with fatigue and the group without fatigue. In almost all patients with fatigue, DEX tapering was performed from the next cycle. The efficacy of DEX tapering was evaluated by comparing the grade and subjective symptoms. Following DEX tapering, the severity of fatigue was significantly reduced (p < 0.05), and the subjective symptom was improved in 94.7% of patients. Therefore, fatigue is occasionally induced after the cessation of DEX administration for supportive therapy in breast cancer patients. The tapering of DEX may be effective for fatigue.