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Using various chromatographic separations, six glycoside derivatives (1–6), including one new ent-labdane glucoside named cayratioside (1), were isolated from the methanol extract of Cayratia geniculata stems and leaves. Their structures were elucidated by detailed analysis of the 1D, 2D NMR, and HRESIQTOF mass spectra. The inhibitory effect of 1–6 on LPS-induced NO production in RAW264.7 cells was also evaluated. Among isolated compounds, 1 exhibited moderate activity with an IC50 value of 59.65 ± 1.85 µM. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusion\nPLAIN LANGUAGE SUMMARYTalquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management.In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices.The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Six participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms.This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.Talquetamab is a new treatment that was approved in the United States in 2023 for a type of blood cancer called multiple myeloma. This drug is administered at one of two doses, each of which includes a defined step-up dosing schedule where patients first receive smaller amounts of the drug to help avoid serious side effects. Because talquetamab is new and associated with treatment-related symptoms not normally seen with other multiple myeloma treatments, doctors and patients need more guidance on drug administration and symptom management. In this study, we describe findings from interviews and an expert panel discussion with healthcare professionals who have experience using talquetamab. This study found that most healthcare professionals administered step-up dosing with patients staying overnight in the hospital, while other providers administered these doses during outpatient visits. Most providers administered talquetamab once every 2 weeks after utilizing the associated step-up dosing schedule. Additionally, healthcare providers described transitioning some patients, who had responded positively to treatment, to a less frequent dosing schedule of once per month to help reduce the effect of treatment-related symptoms. Participants in the expert panel described approaches for managing or preventing these symptoms, such as dexamethasone and nystatin mouthwashes or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. In summary, this study provides valuable real-world information from healthcare providers who have experience treating patients with multiple myeloma with talquetamab. [ABSTRACT FROM AUTHOR]

Purpose: To compare the safety and efficacy of intravitreal injection of ranibizumab alone or ranibizumab combined with dexamethasone intravitreal implant in the treatment of macular edema secondary to retinal vein occlusion. Study design: A single center, case-controlled, prospective cohort study (Clinical Trail Registration Number: ChiCTR2400080048). Methods: A total of 44 patients were enrolled and randomized into the ranibizumab group (n = 23) and the combination group (ranibizumab combined with dexamethasone intravitreal implant) (n = 21). All patients received ranibizumab intravitreal injections in the first three months as the initial treatment. For the ranibizumab group, patients might receive repeat injections in case of the recurrence of macular edema; For the combination group, patients received an intravitreal injection of dexamethasone implant after the first injection of ranibizumab at the day 15. The main outcome was best-corrected visual acuity (BCVA) and reduction of central macular thickness. The secondary outcome were the numbers of recurrence, the average injection interval, and the numbers of injection. Adverse events were also recorded. Results: The BCVAs in both groups were significantly improved compared with the baselines (all p < 0.001), but more increment in BCVA was noticed at the 3-month in the combination group (p = 0.022). Both groups showed a reduction of central macular thickness at all time points (p < 0.05). However, the combination group did not exhibit higher central macular thickness-reducing effects than the ranibizumab group (p > 0.05). Compared with the combination group, the ranibizumab group suffered a higher number of recurrences of macular edema (p < 0.001), a lower interval of injection (p = 0.050), and a higher number of injection (p < 0.011). The incidence of adverse events was not significant between the two groups (p = 0.944). Conclusions: Ranibizumab combined with dexamethasone injection sustainably improved the BCVA of retinal vein occlusion patients with a good safety profile. [ABSTRACT FROM AUTHOR]

Our research aimed to investigate the therapeutic effects of Tubastatin-A, a glucocorticoid receptor (GR) mitochondrial translocation inhibitor, and mitoquinone (MitoQ), an antioxidant, on attenuating dexamethasone (DEX)-induced macrophage apoptosis. We treated RAW264.7 macrophages with different combinations of DEX and either Tubastatin-A or MitoQ. Parameters such as mitochondrial GR translocation, mitochondrial reactive oxygen species levels, mitochondrial membrane potential, mitochondrial permeability transition pore opening, cytochrome C efflux to the cytosol, and apoptosis were subsequently evaluated in the different treatment groups via qRT–PCR, western blotting, and immunofluorescence assays. DEX intervention increased the translocation of GRs into the mitochondria, while reducing the expression of the mitochondrial gene MT-CO1 and the activity of mitochondrial respiratory chain complex IV in macrophages. In addition, DEX administration increased mtROS levels, mitochondrial permeability transition pore opening, and mitochondrial cytochrome C release in macrophages, which promoted their apoptosis. We found that Tubastatin-A inhibited mitochondrial GR translocation and reversed the DEX-induced increase in GR levels within the mitochondria. Furthermore, Tubastatin-A mitigated various mitochondrial changes induced by DEX, including reducing the efflux of mitochondrial cytochrome C and inhibiting macrophage apoptosis. Similarly, MitoQ exerted its effects on macrophage apoptosis by reducing mtROS levels through the mitochondrial pathway. The DEX-mediated translocation of GR into mitochondria disrupts the mitochondrial function of macrophages, which induces their apoptosis. By inhibiting mitochondrial translocation of GR and reducing mtROS levels, Tubastatin-A and MitoQ can effectively attenuate macrophage apoptosis, which has clinical implications for reducing the notable side effects associated with glucocorticoid use. [ABSTRACT FROM AUTHOR]

Dexamethasone (DEX) degradation was investigated using three UV-based advanced oxidation processes combined with sodium persulphate, hydrogen peroxide, and free chlorine in aqueous solutions in a bench-scale reactor. The goal was to determine which process would be the best option in terms of DEX degradation without the subsequent generation of toxic compounds. The process performance for DEX degradation followed the UV/S2O82−> UV/H2O2> UV/HOCl order under equal conditions. In the UV/S2O82− process, sulphate radicals led to a 70.4% DEX degradation. The experimental mineral inhibitory factors showed that nitrite and bicarbonate further decrease the efficiency of the UV/S2O82− process. In the optimal conditions, the UV/S2O8−2 process removed DEX by 100% and had a 74.1% mineralisation. Furthermore, the intermediates were detected using LC-MS/MS, and the cytotoxicity of the UV/S2O8−2 process effluent was evaluated using human embryonic kidney cultured cells. The treatment of DEX solution by the UV/S2O8−2 process significantly decreased the toxicity of the effluent. Therefore, it can be concluded that the UV/S2O8−2 process can be a reliable process for DEX degradation and detoxification in aqueous solutions. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic macular edema (DME) is a vision threatening accumulation of fluid within the macula. Current treatments involve the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF), steroids, and laser to preserve vision. Areas covered: This review covers phase III therapeutics including KSI-301, which targets VEGF-A, UBX1325 which promotes apoptosis of senescent vascular endothelial cells and topical dexamethasone drops. Phase I and phase II therapeutics are also discussed including APX3330, a reduction-oxidation factor (Ref-1) inhibitor, ASP8232 – a vascular adhesion protein-1 (VAP-1) inhibitor, OTT-166, an anti-integrin agent, EYE103, a Wnt agonist and AXT107 and AG-73305, which have both anti-integrin and anti-VEGF functions. Tyrosine kinase inhibitors such as EYP-1901 and AXPALI, and YD312, gene therapies such as 4D–150 and RGX-314. Expert opinion: Current treatments for DME are limited greatly by the need for frequent dosing, treatment adherence, and invasive administration. Newer technologies that promote alternative routes of administration or increased longevity hold promise for the management of DME. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the real-life safety, morphological, and visual outcomes of the dexamethasone intravitreal implant (Ozurdex) in patients with macular edema (ME) within a low-middle-income country (LMIC) setting. Methods: Patients with ME who received Ozurdex injections between 2012 and 2018 were included. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), lens status, and intraocular pressure (IOP) at baseline and last follow-up were compared. Univariate and multivariate analyses identified factors associated with visual improvement. Results: 154 patients were enrolled. Diabetic ME was the most common etiology (32.4%), followed by central retinal vein occlusion (18.8%), branch retinal vein occlusion (14.2%), and uveitis (9.99%). CRT was significantly reduced in all patients except those with uveitis but did not correlate with BCVA improvement. Lower baseline visual acuity (OR=1.67), younger age (OR=1.87), and ME secondary to branch retinal vein occlusion (OR=1.34) were associated with BCVA improvement (p < 0.05). During follow-up, 11 patients (7.14%) developed cataracts, and 22 (14.2%) showed increased IOP; these complications resolved without affecting final BCVA improvement. Conclusion: In an LMIC setting, Ozurdex effectively reduces CRT in diabetic and retinal vein occlusion-related ME but not in uveitis. BCVA improvement depends on factors beyond CRT reduction. Cataracts and elevated IOP are manageable complications. [ABSTRACT FROM AUTHOR]

Objectives: The evaluation of the outcomes of patients undergoing arthroscopic unilateral meniscus repair on receiving intra-articular injection (IAI) of dexmedetomidine (DXM) alone in dose of 2 µg/kg or in dose of 1 µg/kg with other analgesics. Patients & Methods: 150 patients were randomly distributed between 5-groups: C-Group received saline, Study Group I (SI-Group) received DXM 2 µg/kg, SII, SIII and SIV groups received DXM 1 µg/kg with ketamine 0.5 mg/kg, dexamethasone (DXA) 8-mg or ketorolac 30-mg, respectively, with bupivacaine. Bupivacaine spinal anesthesia was provided, and IAI was injected through an arthroscopic port as a single shot. The study outcome is the efficacy of IAI of DXM as judged by pain scores, duration till requesting morphine, times of requesting, and total dose of morphine used during 12-h after IAI. Results: Pain scores and the cumulative scores were significantly lower in the study groups with lower frequency of requests and the total dose of morphine compared to the C-Group with insignificant difference between study groups. The incidence of adverse events was significantly lower in SIII-Group than in other groups. Patients' and surgeons' satisfaction was higher in the study groups than C-Group. Conclusion: The IAI of DXM alone or in combination with any other analgesic is an effective and safe analgesic modality for post-arthroscopic surgeries. All additives were effective in terms of reduction of pain score and opioid consumption, but the side effects of ketamine and duration of analgesia of ketorolac are questionable. However, DXA is an efficient analgesic with minimal side effects. [ABSTRACT FROM AUTHOR]

Background: The pain following a laparoscopic cholecystectomy is multifaceted; Therefore, it can be controlled by multimodal methods such as Transmuscular Quadratus Lumborum Block (TQLB) and analgesics. Objectives: Determine the effectiveness of TQLB using Bupivacaine or Bupivacaine-Dexamethasone in improving the quality of analgesia after laparoscopic cholecystectomy procedures. Methods: Under general anesthesia, ninety patients, ranging in age from eighteen to sixty, were scheduled for elective laparoscopic cholecystectomy surgery. Three groups of patients (30 patients in each) were randomly assigned who underwent bilateral ultrasound guided TQLB injected with 21 ml of the drug on each side. The Bupivacaine group (B) received (20 ml Bupivacaine hydrochloride 0.25% + 1 mL 0.9% normal saline); the Dexamethasone-Bupivacaine group (D) received (20 ml Bupivacaine hydrochloride 0.25% + 1 mL dexamethasone 4 mg); and the Control group (C) received (21 ml 0.9% normal saline). Results: The initial analgesic request was significant longer in group D (18 h) more than B (14 h), and C (0.8 h). The total analgesic requirements were increased in group C. The visual Analogue Score at rest and movement always revealed no significant distinctions between groups B and D. However, all values were raised in the control group more than in the other groups. The percentage of patients who were satisfied with the technique was greater in groups B and D than in group C. Conclusions: Ultrasound guided TQLB is a useful technique for raising patient satisfaction and analgesic quality. Furthermore, the addition of dexamethasone can prolong the duration of analgesia and decrease the postoperative Analgesia requirement. [ABSTRACT FROM AUTHOR]

AbstractPurpose Methods Results Conclusion This study aimed to assess the effectiveness of monocular and bilateral injections of Dexamethasone-21-acetate (Dex-21-Ac) into the murine fornix twice a week as a glucocorticoid-induced ocular hypertension model and investigated potential systemic side effects.Dex-21-Ac was administered twice weekly in three groups: bilateral injections, monocular injections, and a control group receiving the vehicle solution bilateral. After 21 days, enucleated eyes were examined using immunocytochemistry (ICC), and organ histology was performed.All groups receiving Dex-21-Ac injections had a significant increase in intraocular pressure (IOP). Monocular injections also resulted in a significant increase in IOP in the fellow eye. The Dex-21-Ac-treated groups showed a bilateral increase in IOP of approximately 8 mmHg, accompanied by elevated expression of alpha smooth muscle actin and fibronectin in the anterior chamber angle. There were no significant changes in weight progression. Hepatic steatosis was observed in all Dex-21-Ac-treated animals, and some suffered from residual neuromuscular blockade under fentanyl anesthesia.Bilateral injections of Dex-21-Ac twice a week lead to a significant increase in daytime IOP and fibrotic changes in the trabecular meshwork. Unilateral application has a significant impact on the fellow eye. Local dexamethasone leads to notable systemic effects independent of changes in animal weight. Considering liver damage and associated influence on metabolization, hepatically eliminated injection anesthetics may lead to overdosing and are not recommended. They should be replaced by inhalation anesthesia. [ABSTRACT FROM AUTHOR]

Systemic use of Ivermectin has been reported to incite blindness in humans and veterinary patients. This study was designed to investigate the systemic and intravitreal effect of Ivermectin on ocular and retinal health and its attenuation with topical Dexamethasone. Systemic injection of Ivermectin@ 1.6 mg/kg S/C was administered, thrice a week for three weeks to New Zealand White rabbits (N = 4) with and without topical drops of Verapamil (N = 4). Pre and post-treatment ocular examination was conducted. At the end of three weeks the eyes were collected for histopathology. 0.2 ml of Ivermectin solution (1.6 mg/ml) was injected intravitreally in one eye of the rabbit (N = 8), Half the rabbits received 0.1% dexamethasone drops thrice daily for 7 days, while the controls received PBS. Pre and post-treatment, detailed examination was conducted, which included the Schirmer Tear test, Fluorescein staining, Intraocular pressure, slit lamp biomicroscopy and fundus photography. The retina was harvested for histopathological and tunnel assay. Systemic therapy with Ivermectin, with and without Verapamil did not incite any adverse response in the eye. Intravitreal Ivermectin evoked severe uveitis 4/4, cataract 3/4, corneal erosion 3/4 eyes and severe inflammatory response. Eyes that received dexamethasone were rescued from the adverse changes as demonstrated clinically, by histopathology and prevention of apoptosis. Intravitreal Ivermectin incites severe inflammatory response. Topical dexamethasone counters the ocular toxicity incited by Ivermectin. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsThis study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis.Data have been prospectively collected for the period1977–2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5–1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin.In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000).A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients. [ABSTRACT FROM AUTHOR]

Croton antisyphiliticus Mart. is a plant popularly used in folk medicine by traditional communities from Brazilian savannah to treat general inflammation. According to ethnopharmacological data, this specie can be considered a source of biologically active molecules for the development of new drugs. Thereby, this study reports the results of the dereplication approach of C. antisyphiliticus roots extracts and the in vivo evaluation of its potential antinociceptive and anti-inflammatory in albino Swiss mice. Based on HPLC coupled to Q-Exactive Orbitrap Mass Spectrometer and using GNPS, a total of thirteen polyphenolic compounds were noticed, including four compounds that have been reported for the first time in the genus Croton. Ethanolic and aqueous roots extracts demonstrated a dose-dependent inhibition for the number of writes, reduced pain induced by formalin and hyperalgesia induced by carrageenan. These extracts also reduced paw edema, cell migration, and myeloperoxidase activity, with effects similar to indomethacin and dexamethasone drugs. [ABSTRACT FROM AUTHOR]

To evaluate dexamethasone prescribing practices, patient adherence, and outcomes by dosing regimen in children with acute asthma discharged from the emergency department (ED). Prospective study of children 2–18 years treated with dexamethasone for acute asthma prior to discharge from an urban, tertiary care ED between 2018 and 2022. Demographics, clinical characteristics, ED treatment, and discharge prescriptions were collected via chart review. The exposure was discharge prescription (additional dose) versus no discharge prescription for dexamethasone. The primary outcome was treatment failure, defined as return ED visit, unplanned primary care visit, and/or ongoing bronchodilator use. Secondary outcomes included medication adherence, symptom persistence, quality-of-life, and school/work absenteeism. Outcomes were assessed by telephone 7–10 days after discharge. 564 subjects were enrolled; 338 caregivers (60%) completed follow-up. Children were a median age 7 years, 30% Black or African American, 49% Hispanic, and 79% had public insurance. A discharge prescription for dexamethasone was written for 482 (86%) children and was significantly associated with exacerbation severity, number of combined albuterol/ipratropium treatments, and longer length of stay. There was no difference in treatment failure between the discharge prescription and no discharge prescription groups (RR 0.87; 0.67, 1.12), including after adjusting for potential confounders; there was no difference between groups in secondary outcomes. Prescription for an additional dexamethasone dose was not associated with reduced treatment failure or improved outcomes for children with acute asthma discharged from the ED. Single, ED-dose of dexamethasone prior to discharge may be sufficient for children with mild to moderate asthma exacerbations. [ABSTRACT FROM AUTHOR]

Once-weekly carfilzomib at 56 mg/m2 plus immunomodulatory drugs and dexamethasone has shown efficacy and tolerability treating early relapsed/refractory multiple myeloma (RRMM). The phase 2 SELECT study (NCT04191616) evaluated efficacy/safety of weekly carfilzomib, pomalidomide, and dexamethasone (KPd) in early RRMM patients refractory to lenalidomide. All 52 treated patients were refractory to prior treatment, and 19 (37%) were triple-class refractory. Overall response rate (ORR; primary endpoint) was 58% (35% ≥ very good partial response, 6% ≥ complete response); median response duration was 20.3 months. Minimal residual disease negativity (10−5) was achieved in 10% of patients. Median progression-free survival was 11.1 months; median overall survival was 18.8 months. Adverse events (AEs) were consistent with the known safety profile including grade ≥3 treatment-emergent AEs reported in 67% of patients. Although the primary endpoint of ORR was not met, KPd showed meaningful clinical benefits in lenalidomide-refractory RRMM patients, including those who were daratumumab-refractory and/or triple-class refractory. [ABSTRACT FROM AUTHOR]

Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify and compare interventions for treating HSK and their patient outcomes. This systematic review followed the PRISMA methodology. Online databases were searched to obtain all relevant papers. Two independent reviewers screened through 168 records. Seven papers were included and used for data extraction. A qualitative analysis was conducted. HSK patients receiving prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared to patients receiving only acyclovir (P <.001). No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93% and 67% of patients, and BCVA (LogMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine-A (P <.001) and its control (prednisolone) groups (P =.002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group (P <.001). Corticosteroids and antivirals managed HSK most effectively only when used concurrently. Oral acyclovir showed similar effectiveness to its ointment counterpart, a preferable alternative for easier administration. Corticosteroid use could induce greater therapeutic benefits when tapered in concentration and frequency and administrated for at least 10 weeks. Anti-inflammatory drugs including flurbiprofen, cyclosporine-A, and tacrolimus could be safe and effective for treating HSK. Future long-term follow-up and RCTs could provide insights on the therapeutic benefits of these potential alternatives. [ABSTRACT FROM AUTHOR]

In response to the COVID-19 pandemic, this manuscript examines the current standard-of-care treatments in an inpatient and outpatient setting, as well as novel treatment regimens that should be explored. On 29 February 2024, the NIH updated the COVID-19 Treatment Guidelines page for the last time. Over the last 2 years, the treatment options for COVID-19 have remained relatively static. Though there are ongoing studies evaluating inpatient and outpatient therapeutics, most notably the Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) and the Strategies and Treatments for Respiratory Infections and Viral Emergencies (STRIVE) studies, they will both likely end enrollment in 2024. This will leave many promising treatment options without a platform to be tested. It is imperative that we continue to find ways to rigorously test therapeutics, like simnotrelvir, VV116, ensitrelvir and vilobelimab, metformin and a combination of spironolactone and sitagliptin to create better avenues of treatment for patients worldwide. Article highlights Introduction It has now been over 4 years since the start of the COVID-19 pandemic and therapeutic options have remained relatively stagnant, with little improvement in morbidity and mortality. Background SARS-CoV-2 binds to the ACE2 receptor, prompting renin-angiotensin-aldosterone-system dysregulation and a hyper-inflammatory response. Inpatient therapeutics Immunomodulators have been established as the standard of care for patients with moderate to severe COVID-19. Dexamethasone is most often the first-line treatment, but baricitinib and tocilizumab are often given as a second immunomodulator if indicated. New NIH guidelines for inpatient medications The NIH has updated its treatment guidelines for patients who may need an additional immunomodulator. In addition to baricitinib and tocilizumab, abatacept and infliximab are now recommended as a second immunomodulator in some instances. Outpatient therapeutics For nonhospitalized patients, remdesivir, nirmatrelvir-ritonavir and molnupiravir have been used as the standard of care antiviral treatments, yet each of these drugs has limitations. Conclusion Paxlovid remains the preferred therapy for high-risk outpatients, while dexamethasone and remdesivir are the standard treatment for hospitalized patients requiring supplemental oxygen. However, new, better treatment options should continue to be explored, such as simnotrelvir, VV116, ensitrelvir, vilobelimab, metformin and a combination of spironolactone and sitagliptin, especially as the NIH's COVID-19 Treatment Guidelines page will soon be taken down. Future perspective Numerous studies have evaluated COVID-19 therapeutics, but many were limited by observational designs and confounding factors. This highlights the need for more rigorous studies on promising new drugs and the development of rational drug designs. [ABSTRACT FROM AUTHOR]

AbstractDiabetic retinopathy is the most common complication of diabetes and remains the leading cause of vision loss worldwide. The potent glucocorticoid based anti-inflammatory drug dexamethasone (DEX) chosen for the present work is long-acting with half-life of 37–72 h extensively metabolized in to 6-hydroxy-dexamethasone (6-OH-DEX). The present work aimed to develop dexamethasone loaded nanodispersion (DEX-ND) by improving its solubility, half-life, and bioavailability in biological system thereby this formulation may be afforded economically. With the concept that polymeric surfactant improves the solubility of challenging water insoluble drug the present work has been hypothesized to improve its solubility using polyvinyl pyrrolidone (PVP-K30) polymer and polysorbate 80 (Tween 80) hydrophilic non-ionic surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and Tween 80 concentrations three different formulations were developed. The developed DEX-ND was further characterized for its compatibility, particle size, zeta potential, morphology, and in vitro release behavior. The results of Fourier transform infrared spectrometric analysis indicate the compatibility nature of DEX-ND along with other excipients/drug used in the formulation. The developed formulations showed spherical morphology, particle size ranging from 550.46 ± 107.82 to 3560 ± 284.29 nm, zeta potential ranging from −29.23 ± 1.09 to −7.793 ± 1.01 mV. The amount of DEX present in the DEX-NDs was found to be 0.95–3.93 mg. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern. The results of ex vivo corneal permeation studies indicates that the developed DEX- NDs has some exposure to the posterior segment of the eye. [ABSTRACT FROM AUTHOR]

Background/problem: Information transfer between emergency medical services (EMS) and emergency medicine (EM) is at high risk for omissions and errors. EM awareness of prehospital medication administration affects patient management and medication error. In April 2020, we surveyed emergency physicians and emergency department nurse practitioners (NPs) and physician assistants (PAs) regarding the EMS handoff process. Emergency physicians and NPs/PAs endorsed knowing what medications were given, or having received direct verbal handoff from EMS "Often" or "Always" only 20% of the time (n = 71), identifying a need to improve the written handoff process. To assess rates of medication error due to lack of awareness of prehospital administered medications, we measured glucocorticoid redosing in the emergency department (ED) following prehospital dexamethasone administration. In 2020, glucocorticoids were redosed 30% of the time, and our aim was to reduce glucocorticoid redosing to 10% by June 2022. Intervention: We developed and implemented a system innovation where prehospital-administered medications documented in a nursing flowsheet during verbal handoff are pulled directly into the triage note where they are more likely to be reviewed by receiving EM clinicians. Results: Shewhart p-charts were used to evaluate for statistical process change in the process measure of triage note documentation of prehospital medication administration and the outcome measure of glucocorticoid redosing. While the frequency of prehospital dexamethasone administration in the triage note increased, no statistical process change outcome measure of glucocorticoid redosing was observed. However, on repeat survey of EM clinicians in July 2022, 50% now indicated they were aware of prehospital medication administration "Often" or "Always" (n = 61, p = 0.003), 87% maintained they use the triage note as the main source of information regarding prehospital medication administration, and 81% "Always" review the triage note. Conclusions: Innovations that improve accessibility of written documentation of prehospital medication administration were associated with improved subjective assessment of EM clinician awareness of prehospital medications, but not the outcome measure of medication error. Effective error reduction likely requires better system integration between prehospital and EM records. [ABSTRACT FROM AUTHOR]

Paclitaxel hypersensitivity reactions (HSRs) are prevalent, especially in females. The common paclitaxel pretreatment, dexamethasone, may inhibit chemotherapy efficacy and accelerate tumor progression. We aimed to balance paclitaxel HSRs and the lowest dexamethasone dose for gynecologic malignancies. We retrospectively examined 1,074 cycles of 3-weekly paclitaxel-containing treatment for 231 gynecologic malignancies at Xiangya Hospital. HSR incidence with different dexamethasone regimens was the primary outcome. Risk factors were examined in all cycles using univariate and multivariate models with generalized estimating equations. A subgroup analysis of initial exposure to paclitaxel was also conducted. HSR occurred in 33 patients (14.29%) and 49 cycles (4.56%), including 69.39% in cycles 1–2. There were no severe HSRs (grade ≥3). Different premedication regimens, including dexamethasone dosage and route, ranitidine presence or absence, didn't affect HSR incidence in univariate and multivariate analyzes (p > 0.05). Premenopausal women exerted fewer HSRs (ORadj 0.22, 95%CI 0.08–0.58; p = 0.002). At the first exposure to paclitaxel, more than 10 mg of dexamethasone didn't diminish HSRs (OR 0.83, 95%CI 0.27–2.59; p = 0.753). In gynecologic malignancies, 10 mg dexamethasone along with 20 mg diphenhydramine may be adequate to prevent paclitaxel HSRs without ranitidine. It is necessary to reevaluate paclitaxel premedication regimens. [ABSTRACT FROM AUTHOR]

To report a case of ocular toxoplasmosis as a rare complication of intravitreal dexamethasone implant in a case of diabetic macular edema. A 56 years old male, a known case of Proliferative Diabetic Retinopathy, received intravitreal dexamethasone implant for diabetic macular edema in left eye. He developed toxoplasma retinochoroiditis involving the macula with further diminution of vision in his left eye 3 weeks after the injection. His serum titres were positive for Toxoplasma IgG (161 IU/ml). He was treated with oral Sulfamethoxazole 800 mg + Trimethoprim 160 mg 12 hourly for 4 weeks. The visual acuity in left eye improved with resolution of retinochoroiditis after the course of antibiotic therapy. It is imperative to follow-up closely after intravitreal steroid implantation, to look for the possible rare complication of infectious retinitis/retinochoroiditis, as timely antimicrobial treatment can lead to a good visual outcome. [ABSTRACT FROM AUTHOR]

Patients undergoing thyroidectomy often develop hypocalcemia. While there is evidence suggesting that the prophylactic administration of dexamethasone in patients undergoing thyroidectomy can reduce the risk of postoperative complications including nausea, vomiting, and pain, it remains uncertain as to whether such treatment has a similar impact on hypocalcemia risk. Here, randomized controlled trials (RCTs) focused on comparing the risk of postoperative hypocalcemia in thyroidectomy patients that either were or were not administered a single preoperative dose of dexamethasone were systematically evaluated. These RCTs were identified by searching the Medline, PubMed, Embase, and Cochrane Library for all relevant publications as of April 2023. Primary study outcomes included biochemical hypocalcemia and symptomatic hypocalcemia incidence within 24 h after thyroidectomy, while the incidence of permanent hypocalcemia was a secondary outcome in this analysis. Random-effects models were used for all comparisons in this meta-analysis. In total, 8 RCTs enrolling 1666 patients were incorporated when conducting this meta-analysis. Relative to placebo control treatment, dexamethasone administration was associated with significant reductions in the rates of postoperative symptomatic hypocalcemia (OR = 0.40; 95%CI 0.16–1.00; p = 0.050) and biochemical hypocalcemia (OR = 0.34;95%CI 0.14–0.83; p = 0.020 (p < 0.05). No differences were detected between these groups with respect to the incidence of permanent hypocalcemia, and no trials revealed any evidence of glucocorticoid-associated complications. Significant heterogeneity was detected among studies, but the exclusion of any single study did not significantly alter study outcomes. The present pooled analyses suggested that one preoperative dexamethasone dose was sufficient to reduce the odds of thyroidectomy patients developing biochemical or symptomatic hypocalcemia within 24 h after the procedure. The prophylactic administration of steroids was both safe and effective, suggesting that it warrants consideration as a component of routine clinical care. However, additional prospective work will be vital to validate the efficacy of dexamethasone as a means of preventing objective hypocalcemia in this patient population. [ABSTRACT FROM AUTHOR]

Nearly all patients with multiple myeloma eventually relapse or become refractory to treatment. Lenalidomide is increasingly administered in the frontline until disease progression or intolerance to therapy, resulting in the need for highly effective, lenalidomide-sparing options. In this study, carfilzomib plus daratumumab and dexamethasone were evaluated against lenalidomide-sparing, pomalidomide-containing triplets using matching-adjusted indirect comparison in the absence of head-to-head data. The analyses utilized long-term follow-up data from the CANDOR study (NCT03158688). Treatment with carfilzomib, daratumumab, and dexamethasone resulted in significantly longer progression-free survival (hazard ratio 0.60 [95% confidence interval: 0.37, 0.88])vs. pomalidomide plus bortezomib and dexamethasone, and numerically longer progression-free survival (hazard ratio 0.77 [95% confidence interval: 0.50, 1.08]) vs. daratumumab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma and previous lenalidomide exposure, the majority of whom were lenalidomide refractory. Carfilzomib plus daratumumab and dexamethasone offers a highly effective, lenalidomide-sparing treatment option for this population. [ABSTRACT FROM AUTHOR]

Owing to the potentially harmful adverse effects of current anti-inflammatory drugs, there is a need to identify new alternative substances. Thus, this study aimed to perform a phytochemical analysis of A. polyphylla to identify compounds responsible for its anti-inflammatory activity. Several fractions of the A. polyphylla extract were obtained and evaluated in an ex vivo anti-inflammatory assay using fresh human blood. Among the evaluated fractions, the BH fraction displayed the highest percentage of PGE2 inhibition (74.8%) compared to the reference drugs dexamethasone and indomethacin, demonstrating its excellent potential for anti-inflammatory activity. Astragalin (P1), a known 3-O-glucoside of kaempferol, was isolated from the A. polyphylla extract for the first time. In addition, a new compound (P2) was isolated and identified as the apigenin-3-C-glycosylated flavonoid. Astragalin showed moderate PGE2 activity (48.3%), whereas P2 was not anti-inflammatory. This study contributes to the phytochemical studies of A. polyphylla and confirms its anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p <.01). Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique. [ABSTRACT FROM AUTHOR]

We aimed to investigate patterns of corticosteroid use and their relationship with remdesivir use and clinical outcomes in a large real-life cohort of COVID-19 patients treated in a tertiary-level institution. We retrospectively analyzed a total of 1558 severe and critical COVID-19 patients, including 779 patients treated with remdesivir and 779 matched control patients. A total of 167 (10.7%) patients received none, 710 (45.6%) low, 539 (34.6%) high, and 142 (9.1%) very high corticosteroid doses. Patients treated with remdesivir had significantly longer exposure to corticosteroids, received higher average and maximal daily doses, and cumulative corticosteroid doses. In the multivariate analysis remdesivir use, lower cumulative comorbidity burden, higher severity of COVID-19 symptoms, and mechanical ventilation were recognized as mutually independent predictors of the use of higher corticosteroid doses. Higher corticosteroid doses were associated with significantly increased mortality. Among non-remdesivir treated patients, there was a U-shaped relationship between maximal daily corticosteroid dose and mortality. Among remdesivir treated patients gradual increase in mortality with increasing corticosteroid doses was observed. Patterns of corticosteroid use differ regarding the use of remdesivir and may moderate its association with survival among severe and critical COVID-19 patients. [ABSTRACT FROM AUTHOR]

While a range of pharmacological agents are currently used to alleviate inflammation, the clinical administration of many of these anti-inflammatory drugs is associated with high rates of adverse side effects that make them poorly suited to long-term use. Therefore, there is a critical need for the development of novel anti-inflammatory agents. Natural compounds and derivatives like ethyl ferulate have risen to prominence as a foundation for many drug discovery efforts owing to their structural diversity and wide-ranging biological activities. In the present study, 24 ethyl ferulate derivatives were synthesized. Their anti-inflammatory activity was evaluated in vitro using RAW264.7 cells and CCK-8, ELISA, and Western blotting assays. These analyses revealed that most of the synthesized compounds exhibited moderate to high anti-inflammatory activities. In particular, c10 and c23 exerted more pronounced activity than ethyl ferulate or dexamethasone with respect to the suppression of tumour necrosis factor-α production by RAW264.7 cells through the targeting of the NF-κB and MAPK signalling pathways, suggesting that these compounds warrant further investigation. [ABSTRACT FROM AUTHOR]

Some studies have shown a positive effect of systemic corticosteroid on hearing results after stapedotomy, but its side effects can limit its routine administration. The aim of this study was to investigate the effect of local dexamethasone on the results of stapedotomy surgery. Fifty two patients undergone stapedotomy surgery for otosclerosis involved. In the case group after stapedotomy we fulfilled the middle ear with dexamethasone and then the placement of the prosthesis was done. In the control group after stapedotomy we did not use dexamethasone in the middle ear. Gender, age, nausea, vomiting, postoperative vertigo and nystagmus did not significantly differ between the groups. A significant difference was observed in tinnitus rate between two groups. In the case group ABG decrease was higher and bone conduction thresholds improved at frequencies of 1000, 2000, and 4000 three months after surgery. Since local dexamethasone had a positive effect on the results of stapedotomy surgery, it can be used instead of systemic corticosteroids to reduce the side effects and increasing surgery's success rate. If local dexamethasone had a positive influence on the results of stapedotomy surgery, it can be used instead of systemic corticosteroids to reduce the side effects and increasing surgery's success rate. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% vs. 47.6%, CR: 50.0% vs. 26.2%; P < 0.05) and 6 months (OR: 71.4% vs. 45.2%, CR: 42.9% vs. 25.0%; P < .05). Furthermore, patients with anti-GPIb /IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% vs. 78.3%; P < .05) and 6 months (OR: 29.2% vs. 78.3%; P < .05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, P = .003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients. [ABSTRACT FROM AUTHOR]

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

Primary hepatocytes are widely used as a tool for studying metabolic function and regulation in the liver. However, the metabolic properties of primary hepatocytes are gradually lost after isolation. Here, we illustrated that fatty acid metabolism is the major compromised metabolic process in isolated primary hepatocytes, along with drastically decreased GSH and ROS content, while lipid peroxidation is increased. Gain- and loss-of-function studies revealed that Slc7a11 expression is critical in maintaining fatty acid metabolism and facilitating hormone-induced fatty acid metabolic events, which is synergistic with dexamethasone treatment. Intriguingly, Slc7a11 expression and dexamethasone treatment cooperatively upregulated AKT and AMPK signaling and mitochondrial complex expression in primary hepatocytes. Furthermore, direct treatment with reduced GSH or inhibition of ferroptosis is sufficient to drive protective effects on fatty acid metabolism in primary hepatocytes. Our results demonstrate that Slc7a11 expression in isolated primary hepatocytes induces GSH production, which protects against ferroptosis, to increase fatty acid metabolic gene expression, AKT and AMPK signaling and mitochondrial function in synergy with dexamethasone treatment, thereby efficiently preserving primary hepatocyte metabolic signatures, thus providing a promising approach to better reserve primary hepatocyte metabolic activities after isolation to potentially improve the understanding of liver biological functions from studies using primary hepatocytes. [ABSTRACT FROM AUTHOR]

Background: Erector spinae plane (ESP) block has been evaluated in many studies in pediatric surgeries by the use of postoperative rescue analgesia which is the objective parameter assessing the efficacy of the technique in controlling postoperative pain. Adjuvants were used with ESP block to densify its postoperative analgesia. Magnesium sulfate was used for suppressing somatic, endocrine and autonomic reflexes induced by noxious stimuli during surgery. Dexamethasone is a highly potent glucocorticoid that has been used in different regional anesthesia to prolong the anesthetic effect of the local anesthesia by inducing local vasoconstriction. Methodology: Sixty pediatric patients underwent inguinal hernia repair under general anesthesia, and then they were assigned randomly into three groups that received ESP block either with local anesthetic alone or with magnesium sulfate or dexamethasone. Results: Our study revealed no statistical significance among the three groups as regards demographic and vital data. Children's Hospital Eastern Ontario Pain Scale score for postoperative assessment of magnesium sulfate and dexamethasone which were added to bupivacaine in ESP block had a better score than bupivacaine alone with high statistical significance. Also, magnesium sulfate and dexamethasone had a delayed first-dose postoperative rescue analgesia with significant statistical value (P value = 0.002) and total postoperative doses of postoperative rescue analgesia were lesser in magnesium sulfate and dexamethasone groups with marked statistical significance (P value < 0.001). As regards complications, there were minor ones in the form of mild bruising and mild pain at injection site with no statistical significance between the three groups (P value = 0.108). Conclusion: In our study, magnesium sulfate and dexamethasone added to bupivacaine in ESP block prolonged the duration of postoperative pain control and decreased the consumption of postoperative analgesia than bupivacaine alone. No major complications were recorded in our study in the three groups which solidify the safety of the technique. [ABSTRACT FROM AUTHOR]

To compare endothelial toxicity and efficacy of two local steroid injections (intracameral triamcinolone acetonide and subconjunctival dexamethasone) in controlling postoperative inflammation following pars plana vitrectomy (PPV) combined with phacoemulsification cataract surgery. This cohort included 54 patients that underwent combined surgery and received either intracameral triamcinolone acetonide injections (n = 27, IC-TA group) or subconjunctival dexamethasone (n = 27, Sc-Dex group) injections at the end of the surgery. All participants had at least 4 months or longer follow-up. A detailed ophthalmologic examination including intraocular pressure (IOP) measurement and specular microscopy was performed at every visit. Endothelial cell density (ECD) reduced significantly in IC-TA group postoperatively (2418 vs. 2249, p = 0.019), while it did not change significantly in Sc-Dex group (2541 vs. 2492, p = 0.247). Postoperative ECD was also significantly lower in IC-TA group compared to Sc-Dex group (p = 0.011). Preoperative and postoperative IOP values remained unchanged both in IC-TA and Sc-Dex groups (p = 0.424 and p = 0.523, respectively). However, 4 patients in IC-TA group and 5 patients in the Sc-Dex group needed glaucoma medications. The postoperative need for glaucoma medications was similar between the groups (p = 0.347). Postoperative inflammation was well controlled in both groups and none of the patients developed fibrin membrane or synechiae postoperatively. Both treatments were effective in controlling postoperative inflammation, but patients in IC-TA group experienced significantly higher endothelial loss. Sc-Dex injections are safer in terms of endothelial loss and preferable to control postoperative inflammation following complex intraocular surgeries. [ABSTRACT FROM AUTHOR]

An 82-year-old male presented with generalised Pityriasis rubra pilaris (PRP) managed initially by dermatology team. The patient did not respond to first- and second-line treatment, including oral acitretin, steroid creams, and methotrexate, and developed bilateral cicatricial ectropion, for which he was referred to oculoplastic team for surgical management. A head injury resulting in subacute subdural haematoma, managed with a week course of low dose oral dexamethasone, resulted in the improvement of his skin condition and complete resolution of the cicatricial ectropion within a few weeks. Thus, systemic treatment of PRP with oral dexamethasone may be considered sooner in the treatment of cicatricial ectropion in similar cases. [ABSTRACT FROM AUTHOR]

Pain is prevalent after most TransOral Robotic Surgery (TORS) procedures and may limit function i.e. swallowing. Currently, there is limited knowledge regarding optimal pain treatment in TORS. This clinical trial randomized patients to either a high-dose dexamethasone or low-dose dexamethasone treatment in addition to a multimodal basic analgesic protocol. The aim of the trial was to investigate the pain intensity during rest and swallowing using the Visual Analogue Scale (VAS) after TORS lingual tonsillectomy. Secondary outcomes were acceptable food consistency, nausea, vomiting, opioid rescue usage, length of hospitalization, feeding tube placements, readmissions, blood glucose levels and postoperative complications. The trial was conducted between August 2020 and October 2022. Eligible patients were patients scheduled for TORS-L treatment of obstructive sleep apnea syndrome or as part of the diagnostic work-up of head and neck carcinoma of unknown primary. Eighteen patients were and randomized 1:1. There were overall no significant differences between groups in the reported VAS scores during rest or swallowing (p ≥.05). Overall, there were no differences in the secondary outcomes. There were no differences in the pain intensity in the two treatment groups allocated to a basic multimodal analgesic package and either high-dose dexamethasone or low-dose dexamethasone treatment. The trial is the first RCT to include pain measurement during a procedure-relevant activity, thus creating a platform for future recovery studies. [ABSTRACT FROM AUTHOR]

Alcoholic extract and its ethyl acetate fraction of Moringa oleifera (Lam.) (MO), (Moringaceae) bark are experimentally claimed to possess insulin-sensitizing potentials. The present study aimed to isolate and characterize the phytochemical(s) responsible for insulin sensitization in dexamethasone-induced acute and chronic rat models for insulin resistance (IR). The reported ethyl acetate fraction from the alcoholic extract of the bark of MO was prepared and subjected to bioactivity-guided sub-fractionation and isolation of phytochemicals. A component responsible for improving insulin sensitivity in rat models for IR was isolated and reported for the first time from the bark of MO and its structure was characterized as a procyanidin dimer type of polyphenol by spectroscopic techniques. [ABSTRACT FROM AUTHOR]

To study the long-term efficacy and safety of Ozurdex as anti-inflammatory monotherapy in the management of tuberculosis-associated intermediate uveitis (TBIU). Retrospective analysis of eyes with TBIU that received Ozurdex as anti-inflammatory monotherapy with a follow-up of at least 1 year. 13 eyes (2 pseudophakic) of 11 patients were included. Mean BCVA improved from 0.65 to 0.11 at 3 months (p =.0005) and remained 0.11 at 1 year. Mean central foveal thickness improved from 452.87µ to 187.25µ at 3 months (p =.0009) and 184.62µ at 1 year in 8 eyes with CME. Mean vitreous haze improved from 2.38 to 0.11 at 3 months with no recurrences at 1 year. Mean IOP increased from 13.15mmHg to 15.53mmHg (p =.013) at 2 months and reduced to 12.46mmHg by 1 year. None required antiglaucoma medication. One eye underwent cataract surgery. The mean follow-up was 18.4 months. Ozurdex is safe and efficacious in TBIU as anti-inflammatory monotherapy in conjunction with antitubercular therapy. [ABSTRACT FROM AUTHOR]

To investigate the single-dose effect of intravitreal dexamethasone (DEX) implant for patients with post-vitrectomy macular edema (ME) under silicone oil (SO) tamponade. Twelve eyes diagnosed with ME after undergoing pars plana vitrectomy with SO injections were retrospectively reviewed. Each eye received a single intravitreal DEX implant (0.7-mg, Ozurdex; Allergan Inc) injection as treatment for recalcitrant ME. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were recorded. Compared with baseline (1.24 ± 0.34), the mean LogMAR BCVA improved at 1 (1.14 ± 0.27), 3 (1.13 ± 0.22), and 6 (1.22 ± 0.30) months without statistical significance. Maximal CMT resolution was observed at 1 month after intravitreal injection. The CMT value improved significantly at 1 (P =.008), 3 (P =.006), and 6 (P =.009) months. IOP did not show significant elevation during follow-up. No serious adverse events were observed. Single-dose treatment of DEX implant may have benefit for recalcitrant post-vitrectomy ME under SO tamponade. [ABSTRACT FROM AUTHOR]

Drug molecules cannot suitably permeate the cornea, but nano eye-drops may be used to improve intraocular drug permeation. We synthesized a homodimeric prodrug of dexamethasone in an anti-inflammatory drug with carbon chain linkers of varying lengths to establish a new prodrug and fabricated the corresponding dexamethasone nanoparticles. A longer carbon chain linker reduces the size of the nanoparticles and increases their hydrolysis resistance. The fabricated nanoparticles permeate into rat eye and then hydrolyze to release the drug. Thus, nano eye-drops seem to be a promising solution for the development of anti-inflammatory drugs with high intraocular permeation. [ABSTRACT FROM AUTHOR]

The reported hospital length of stay (LOS) following transoral robotic surgery lingual tonsillectomy (TORS-L) is variable, with limited understanding of the factors requiring hospitalization and no evidence-based criteria for discharge. This observational cohort study investigated factors hindering discharge following TORS-L in a well-defined postoperative care program. Patients were included between August 2020 and October 2022. A discharge scheme was filled out twice daily, specifying the factor(s) for hospitalization among patients undergoing TORS-L. This trial was a sub-investigation of a national multicentre randomized clinical trial (RCT) testing the efficiency of high-dose dexamethasone on postoperative pain control. Participation in the RCT demanded admission to the fourth postoperative day as dexamethasone/placebo was given intravenously in repeated dosages till day 4 postoperatively. Eighteen patients were included in the analysis. The main factor for hospitalization was nutritional difficulties, while pain was a limiting factor for discharge only on the first postoperative 1-3 days. More than half of the patients could have potentially been discharged on postoperative day 2 when omitting the RCT treatment plan in the analysis. The study estimates that the majority of patients may be discharged on postoperative day 2 following TORS-L. [ABSTRACT FROM AUTHOR]

A multitude of stressors exists in broiler chickens including oxidative stress and inflammation response. Both oxidative stress and inflammation response can activate apoptosis. Melatonin (ML) is a potent antioxidant and inflammatory agent. This study evaluated the effect of melatonin on oxidative stress, inflammation cytokines, biochemical parameters and growth performance in broiler chicken under induced stress by dexamethasone. Three hundred 1-day old broiler chicks were randomly distributed to four treatments as follows: positive control (without DEX), negative control (NC, with DEX) and NC + 30 and 60 mg/kg ML. Melatonin supplementation at the level of 60 mg improved the growth performance, and antioxidant status of stressed birds. The DEX-induced effect on IL-6 and IL-10 was ameliorated by ML supplementation. The heterophil, and activities of AST, ALT and ALP were decreased by ML supplementation. This implies that dietary ML may be useful for ameliorating the negative effect of stress in broiler chickens. [ABSTRACT FROM AUTHOR]

Systemically administered steroids are widely utilised for hearing preservation therapies. More recently, steroids have been administered to achieve hearing protection after cochlear implant surgery. Currently there is a lack of understanding as to which administration route offers most therapeutic efficacy, local or systemic administration. Paramount to this are observations in animal studies that systemic administration following implantation offers hearing protection and reduced cochlear fibrosis, despite observations that perilymphatic levels are up to 10-fold higher after local administration in non-implanted cochleae. This paper explores the impact that cochlear implantation and associated acute inflammation has on steroid distribution and uptake following systemic administration of dexamethasone. Eight guinea pigs received systemic dexamethasone 60 min prior to cochlear implantation. Implanted and contralateral non-implanted cochlea were harvested for tissue immunohistochemistry and detection of dexamethasone. Cochleostomy with scala tympani implantation resulted in a significant increase in cochlear dexamethasone signal. This was most notable at the organ of Corti, stria vascularis, and blood product in the scala tympani. This study demonstrates that the inner ear distribution of systemically administered steroids is enhanced following surgery for cochlear implantation and provides rationale for systemic perioperative steroids in hearing preservation surgery. [ABSTRACT FROM AUTHOR]

Manières disease (MD) is a chronic inner ear disease characterized by recurrent vertigo and fluctuation in auditory symptoms. Vertigo spells have a sudden onset and are difficult for patients to handle. Therefore, treating a patient with MD is still a challenge for clinicians. This study aims to analyse the short-term effects of intratympanic dexamethasone (ITD) on the various symptoms of unilateral MD. The study comprised 27 patients with unilateral MD and severe vertigo who failed medication therapy. Treatment was with ITD as an alternative to destructive therapy. Treatment is evaluated after four months. Significant improvements were measured with Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), frequency of vertigo attacks longer than 20 min, Functional Level Scale (FLS), and tinnitus sensation measured by the Analog Visual Scale (AVS). Patients with severe symptoms grading with DHI and THI experienced the most improvement. Patients have achieved substantial vertigo control in 73%. ITD application shows improvement in controlling vertigo and tinnitus in patients under exacerbation in MD. It is a promising non-destructive addition to the 'stepwise treatment concept' in MD and can be used as a first-line treatment in vertigo control. [ABSTRACT FROM AUTHOR]

Acute asthmatic exacerbation is a common condition for pediatric emergency visits. Recently, dexamethasone has increasingly been used as an alternative to prednisone. This study aimed to evaluate the safety and efficacy of dexamethasone (DEX) against prednisone/prednisolone (PRED) in managing pediatric patients with acute asthmatic exacerbation. Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to August 2022 by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42022353462). From 316 studies screened, seventeen studies met the eligibility criteria, with 5967 pediatric patients experiencing an asthma exacerbation requiring treatment with either DEX (n = 2865) or PRED (n = 3102). Baseline patient characteristics (age, sex, PRAM (pediatric respiratory assessment measure), previous corticosteroid and beta-agonist inhaler) were comparable between groups. After treatment administration, the DEX group had fewer vomiting incidents (OR = 0.24, 95% CI: 0.11, 0.51, I2 = 58%) and reduced noncompliance events (OR = 0.12, 95% CI: 0.04, 0.34, I2 = 0%) when compared to the PRED group. Regarding emergency-department (ED)-related outcomes, there were no differences in hospital admission rates (OR = 0.83, 95% CI: 0.58, 1.19, I2 = 15%), time spent in the ED (MD= −0.11 h, 95% CI: −0.52; 0.30, I2 = 82%) or relapse occurrences (OR = 0.67, 95% CI: 0.30, 1.49, I2 = 52%) between both groups. Although there were no differences between the DEX and PRED groups in terms of hospital admission rates, time spent in the ED or relapse events, pediatric patients receiving DEX experienced lower noncompliance and vomiting rates. [ABSTRACT FROM AUTHOR]

Acute facial-nerve injury. To investigate the effects of platelet-rich fibrin (PRF) and dexamethasone on nerve regeneration. Thirty-six rats were randomly divided into six groups. Facial-nerve injury was created using a full-thickness incision in all groups except Group E. Next, primary anastomosis, PRF application, topical dexamethasone application, primary anastomosis with topical PRF and dexamethasone application, and no facial-nerve repair were performed in Groups A, B, C, D, and F, respectively. Clinical, functional, and structural improvements were evaluated at eight weeks. The mean eye-closure movement score in Group B was significantly higher than that in Group F (p <.001). The mean whisker-movement score in Group B was significantly higher than that in Group F (p =.001). The mean amplitude of whisker movement in Group F was significantly lower than those in Groups A, B, C, and E, and the mean amplitude in Group D was significantly lower than that in Group E (p <.001). Furthermore, an improvement in nerve ultrastructure was observed in Group B. PRF application has a positive effect on nerve recovery after anastomosis. Contribute to the literature to improve nerve regeneration. [ABSTRACT FROM AUTHOR]

Ajuga multiflora Bunge is a perennial ornamental herb and has been used for the treatment of fever in Korean folk medicine. In the course of searching for protective agents associated with the potential of A. multiflora against dexamethsone (DEX)-induced muscle atrophy, a new phytoecdysteroid, 29-hydroxyprecyasterone (1), together with four known compounds (2–5), were isolated from A. multiflora. The structures of the compounds were determined by spectroscopic analyses, including 1D-, 2D-NMR and HR-MS interpretation. To elucidate the effects of obtained compounds on DEX-induced muscle atrophy, the myotubes diameter, myosin heavy chain (MyHC) positive area, and fusion index were evaluated by immunofluorescence staining. Overall, each compound treatment effectively prevented the atrophic myotubes through an increase of MyHC-positive myotubes and the number of nuclei. Particularly, the measurement of myotube diameter showed that compounds 1 and 5 treatment significantly alleviated the myotube thickness. [ABSTRACT FROM AUTHOR]

Siparuna brasiliensis is a medicinal plant widely used by indigenous communities of the Amazon rainforest to treat inflammatory diseases and related pathologies. Considering its ethnopharmacological application, it constitutes an important source of biologically active molecules in the development of anti-inflammatory drugs. This study describes a dereplication methodology of the bioactive extract from S. brasiliensis leaves and the evaluation of the anti-inflammatory potential in an in vivo inflammatory model with mice of the BALB/c lineage and in vitro using cell lines, as well as determining the production of an inflammatory mediator. From their charge-to-mass ratios (m/z) and elemental composition obtained through Ultrahigh-resolution mass spectrometry analysis by ESI(-)-Orbitrap MS and chromatographic profile by RP-HPLC-PDA, it was possible to annotate polyphenols with anti-inflammatory properties classified as flavonoids and organic acids. The administration of the extract significantly inhibited carrageenan-induced paw edema and showed effects similar to those of drug dexamethasone without affecting cell viability. [ABSTRACT FROM AUTHOR]

The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37–0.57) and 0.47 (95% confidence interval, 0.39–0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups. [ABSTRACT FROM AUTHOR]

To compare efficacy of simultaneously administered intravitreal dexamethasone implant (DEX implant) and ranibizumab (simultaneous double protocol) injections with ranibizumab monotherapy for diabetic macular edema (DME) at month 24. This is a prospective, consecutive, clinical interventional study. Naïve eyes with DME were randomized into two groups: 34 eyes received simultaneous double-protocol therapy and 34 eyes received ranibizumab monotherapy. The primary efficacy endpoint was change in visual acuity in month 24. The secondary efficacy endpoints were to evaluate gain of ≥15 letters, morphological changes and central foveal thickness. Decreased vision from DME (study eye BCVA, 20/40 or worse Snellen equivalent using ETDRS testing), the presence of DME with ≥300 μm foveal intraretinal cystoid spaces (within 1000 μm of the centre of the fovea), subfoveal neuroretinal detachment (SND), intraretinal hyperreflective foci (HRF, within 500 μm of the centre of the fovea) or foveal lipid exudates and external limiting membrane (ELM) and ellipsoid zone (EZ) disruption (within 500 μm of the centre of the fovea) on SD-OCT were eligible to enrol. The mean baseline BCVA was 48 ± 23 letters in double protocol group and 52 ± 14 letters ranibizumab monotherapy group (p = 0.416). The mean number of ETDRS letters changed from baseline at 12 months versus change from baseline at month 24 in double protocol group and ranibizumab monotherapy group were +21.6 versus +20.2 and +9.6 versus +9.1, respectively. At the month 24 time point, 65.4% of patients in double protocol group and 26.2% of patients in ranibizumab monotherapy group had gained ≥15 ETDRS letters in BCVA from baseline (p < 0.001). The external limiting membrane (ELM) and ellipsoid zone (EZ) integrity were better in the double protocol group in comparison to ranibizumab monotherapy group at month 24. In addition, there was no statistically significant increase in the proportion of patients with epiretinal membrane in double protocol group at month 24, by the contrast with ranibizumab monotherapy group (p = 0.06 and p = 0.04 in the double protocol and ranibizumab monotherapy groups, respectively). From baseline to month 24, the mean central foveal thickness (CFT) was 672 ± 293 μm reduced to 278 ± 84 μm in double protocol group and was 631 ± 279 μm reduced to 356 ± 108 μm in ranibizumab monotherapy group (p < 0.001 and p < 0.001). From baseline to month 24, 38% (13/34) of eyes in double protocol group and 18% (6/34) of eyes in ranibizumab monotherapy group had at least 5 mmHg of IOP elevation (p = 0.012). Two grades or more increased cataract density were detected 27% (6/22) of eyes in the double protocol group and in 12.5% (3/24) of eyes in the ranibizumab monotherapy group from baseline to month 24 (p = 0.032). According to the improvements in visual acuity and morphological changes achieved at month 24, the simultaneous double protocol therapy can be an effective treatment option for DME with inflammatory biomarkers on OCT or/and decreased visual acuity. [ABSTRACT FROM AUTHOR]

To assess the effects of naproxen sodium-codeine phosphate, naproxen sodium-dexamethasone, and naproxen sodium on myofascial pain. This randomized, double-blind prospective clinical study was conducted with patients who applied with the complaint of pain in the temporomandibular region. A total of 169 patients were randomly divided into four groups and received the following treatments: Group A: naproxen sodium 550 mg; Group B: naproxen sodium 550 mg + codeine phosphate 30 mg; Group C: naproxen sodium 550 mg + single-dose dexamethasone 8 mg, and Group D: paracetamol 500 mg. Of the patients, 132 were female, and 37 were male, with a mean age of 27.04 ± 10.56 (18–69 years). Analgesic efficiency of the naproxen sodium-codeine phosphate group was the most effective at the 2nd week and 4th week (p < 0.05). Naproxen sodium-codeine phosphate might be preferred as an analgesic in similar cases with severe myofascial pain. [ABSTRACT FROM AUTHOR]