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ABSTRACT Purpose: To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. Methods: This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. Results: In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). Conclusions: In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

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BACKGROUND: Experimental models of neurocysticercosis (NCC) are helpful for an improved understanding of the pathophysiological mechanisms of human diseases and for testing novel therapeutic approaches. Controlling inflammation without reducing the effectiveness of anthelmintics is an important challenge in treating neurocysticercosis. This study investigates the effects of currently used drugs (Albendazole and Dexamethasone) in treating murine extraparenchymal NCC. METHODS: Twenty-two rats were inoculated with Taenia crassiceps in the subarachnoid space. The animals underwent magnetic resonance imaging to ascertain the success of infection 3 months after inoculation. The infected animals were randomly assigned to one of the three groups (five rats each): control (no treatment), Albendazole (ABZ), or Albendazole + Dexamethasone (ABZ + DXM) for 14 days. The animals were subsequently euthanised for morphological assessment 2 weeks after the end of treatment. RESULTS: Macroscopically integrated cysts were found in all animals. The ABZ + DXM animals demonstrated lower ventricular sizes, lymphocyte infiltration rates, and immunopositivity for IL-6, with statistical differences in lymphocytes within the arachnoid region. CONCLUSIONS: This experimental model, which has previously shown similarities to human infections, is also helpful in reproducing the morphological changes upon treatment with Albendazole and Dexamethasone.

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Due to its extensive use as a painkiller, anti-inflammatory, and immune modulatory agent, as well as its effectiveness in treating severe COVID-19, dexamethasone, a synthetic glucocorticoid, has gained attention not only for its impact on public health but also for its environmental implications. Various studies have reported its presence in aquatic environments, including urban waters, surface samples, sediments, drinking water, and wastewater effluents. However, limited information is available regarding its toxic effects on nontarget aquatic organisms. Therefore, this study aimed to investigate the mechanism of toxicity underlying dexamethasone-induced brain damage in the bioindicator Danio rerio following long-term exposure. Adult zebrafish were treated with environmentally relevant concentrations of dexamethasone (20, 40, and 60 ng L-1) for 28 days. To elucidate the possible mechanisms involved in the toxicity of the pharmaceutical compound, we conducted a behavioral test battery (Novel Tank and Light and Dark tests), oxidative stress biomarkers, acetylcholinesterase enzyme activity quantification, histopathological analysis, and gene expression analysis using qRT-PCR (p53, bcl-2, bax, caspase-3, nrf1, and nrf2).The results revealed that the pharmaceutical compound could produce anxiety-like symptoms, increase the oxidative-induced stress response, decrease the activity of acetylcholinesterase enzyme, and cause histopathological alterations, including perineuronal vacuolization, granular and molecular layers deterioration, cell swallowing and intracellular spaces. The expression of genes involved in the apoptotic process (p53, bax, and casp-3) and antioxidant defense (nrf1 and nrf2) was upregulated in response to oxidative damage, while the expression of the anti-apoptotic gene bcl-2 was down-regulated indicating that the environmental presence of dexamethasone may pose a threat to wildlife and human health.

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Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

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Chronic and excessive glucocorticoid (GC) exposure can cause Cushing's syndrome, resulting in fat accumulation in selected body areas. Particularly in the brown adipose tissue (BAT), GC acts negatively, resulting in whitening of the tissue. We hypothesized that dysregulation of microRNAs by GC could be an additional mechanism to explain its negative actions in BAT. Male Wistar rats were divided into two groups: (1) Control sham and (2) GC group that was administered dexamethasone 6.25 mg/200 µL via osmotic pump implantation over 28 days. After this period, the animals were euthanized and BAT tissue was properly stored. Human fat cells treated with dexamethasone were used to translate the experimental results found in animals to human biology. GC-treated rat BAT presented with large lipid droplets, severely impaired thermogenic activation, and reduced glucose uptake measured by 18F-FDG PET/CT. GC exposure induced a reduction in the mitochondrial OXPHOS system and oxygen consumption. MicroRNA profiling of BAT revealed five top-regulated microRNAs and among them miR-21-5p was the most significantly upregulated in GC-treated rats compared to the control group. Although upregulation of miR-21-5p in the tissue, differentiated primary brown adipocytes from GC-treated rats had decreased miR-21-5p levels compared to the control group. To translate these results to the clinic, human brown adipocytes were treated with dexamethasone and miR-21-5p inhibitor. In human brown cells, inhibition of miR-21-5p increased brown adipocyte differentiation and prevented GC-induced glucose uptake, resulting in a lower glycolysis rate. In conclusion, high-dose GC therapy significantly impacts brown adipose tissue function, with a notable association between glucose uptake and miR-21-5p.

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INTRODUCTION: Secondary genetic alterations, which contribute to the dysregulation of cell cycle progression and lymphoid specialization, are frequently observed in B-cell precursor acute lymphoblastic leukemia (B-ALL). As IKZF1 and BTG1 deletions are associated with a worse outcome in B-ALL, this study aimed to address whether they synergistically promote glucocorticoid resistance. METHODS: Small interfering RNA was used to downregulate either IKZF1, or BTG1, or both genes in the 207 B-ALL cell line. Cell viability was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. The expression levels of IKZF1, BTG1 and glucocorticoid-responsive genes (DUSP1, SGK1, FBXW7 and NR3C1) were evaluated by real time quantitative real time polymerase chain reaction (PCR). RESULTS: Isolated silencing of BTG1, IKZF1, or both genes in combination under dexamethasone treatment increased cell viability by 24%, 40% and 84%, respectively. Although BTG1 silencing did not alter the expression of glucocorticoid-responsive genes, IKZF1 knockdown decreased the transcript levels of DUSP1 (2.6-fold), SGK1 (1.8-fold), FBXW7 (2.2-fold) and NR3C1 (1.7-fold). The expression of glucocorticoid-responsive genes reached even lower levels (reducing 2.4-4 fold) when IKZF1 and BTG1 silencing occurred in combination. CONCLUSIONS: IKZF1 silencing impairs the transcription of glucocorticoid-responsive genes; this effect is enhanced by concomitant loss of BTG1. These results demonstrate the molecular mechanism by which the combination of both genetic deletions might contribute to higher relapse rates in B-ALL.

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BACKGROUND: To study the effects of various courses of dexamethasone (DEX) combined with 5-HT3 receptor antagonists (RA) and NK-1 RA in suppressing high-grade nausea and vomiting (CINV) caused by anthracycline and cyclophosphamide chemotherapy regimens (AC or EC) in breast cancer (BC) patients. PATIENTS AND METHODS: A prospective study was performed with 252 BC patients who received AC between January, 2019 and June, 2022 in our hospital. Patients were randomly separated into control Group (N = 130) who received DEX 12 mg on day 1 and 8 mg per dose on day 2-4 and observation group (N = 122) treated with DEX 5 mg per dose on days 1-4. The response was monitored. Primary study endpoint was complete resolution (CR) of patients nausea or vomiting; secondary study endpoints included acute CR and delayed CR; and complete control (CC), acute CC, delayed CC, and safety. RESULTS: All patients underwent six rounds of chemotherapy, and no difference was found in the clinical data. CR of acute/delayed phase was (94.3%/88.5%, P > 0.05), (89.3%/90.8%, P > 0.05); total CR was (80.3%/81.5%, P > 0.05); CC was (56.6%/59.2%, P > 0.05), (64.8%/67.7%, P > 0.05); total CR was (48.4%/53.1%, P > 0.05). CONCLUSIONS: The preventive antiemetic effects of NEPA, a fixed-dose combination of netupitant and palonosetron combined with DEX 5 mg per dose on days 1-4, can be similar to DEX 12 mg on day 1 and 8 mg per dose on days 2-4, low-dose hormone with better safety, which is beneficial.

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CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

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The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.

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OBJECTIVE: To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. MATERIALS AND METHODS: A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO2)], and sedation assessed by the Ramsay scale. RESULTS: A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48 h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO2 between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects. CONCLUSIONS: Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect. CLINICAL RELEVANCE: The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.

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The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progression-free survival (HR 0.52; 95% CI 0.43-0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63-0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26-1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02-1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38-2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13-1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.

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PURPOSE: To evaluate the short-term effects (hours-days) of intravitreal dexamethasone implant (IDI) in eyes with diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) injections. METHODS: This was a prospective, single-arm, interventional clinical series. Eyes with DME and 3-9 injections of ranibizumab without a good response were included. Patients underwent a single IDI. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline, 2 h, 3 h, 24 h, 7 days, and 1 month. The main outcomes were change in central retinal thickness (CRT) on SD-OCT and BCVA. RESULTS: Fifteen eyes of 15 patients were included. Mean CRT decreased after treatment from 515.87 µm ± 220.00 µm at baseline to 489.60 µm ± 176.53 µm after 2 h (p = 0.126), and 450.13 µm ± 163.43 at 24 h (p = 0.006). Change in BCVA was from 0.85 ± 0.44 logMAR baseline to 0.58 ± 0.37 log MAR at 1 month (p = 0.003). CONCLUSIONS: Eyes treated with IDI showed significant decrease in CRT detectable 1 day after injection. In some patients, the effect could be observed 3 h post-implantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT05736081 . Registered 20 February 2023, Retrospectively registered.

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Abstract Background: Due to the COVID-19 pandemic, randomized clinical studies were conducted with Remdesivir in combination with Bariticinib or Dexamethasone, which have shown effectiveness for the treatment of COVID-19. Objective: We analyzed the effect of co-treatment with Remdesivir in a retrospective in Mexico. Methods: Thirty-four patients treated with Remdesivir in combination with Baricitinib or Dexamethasone were included. Age, sex, comorbidities, signs, and symptoms were recorded at hospital admission, intubation needs, intensive care unit (ICU) requirements, days of hospital stay and their evolution, as well as laboratory data upon admission and upon admission terminate Remdesivir treatment. Results: Most were male, with an age of 56.5 years (49 years-60.3 years), whose main comorbidity was obesity. The main symptoms on admission were dyspnea and cough. Thirty-two patients received the short Remdesivir regimen, 22 were co-treated with Baricitinb and 12 with Dexamethasone. Most did not require ICU care, 9 patients died, 19% of those co-treated with Baricitinib and 42% of those co-treated with Dexamethasone. A significant decrease in hemoglobin, protein, albumin and LDH levels was observed. Conclusion: In this study, we observed lower mortality in patients co-treated with Baricitinib vs those co-treated with Dexamethasone, and a hospital stay similar to that reported in randomized clinical studies.

Resumen Introducción: Debido a la pandemia de COVID-19, se realizaron estudios clínicos aleatorizados con Remdesivir en combinación con Bariticinib o Dexametasona, que han demostrado efectividad para el tratamiento de COVID-19. Objetivo: Se realizo un análisis del efecto del co-tratamiento con Remdesivir en una muestra retrospectiva en México. Métodos: Se incluyeron 34 pacientes tratados con Remdesivir en combinación con Baricitinib o Dexametasona. Se registraron edad, sexo, comorbilidades, signos y síntomas al ingreso hospitalario, necesidades de intubación, requerimientos de unidad de cuidados intensivos (UCI), días de estancia hospitalaria y su evolución, así como datos de laboratorio al ingreso y al ingreso al final del tratamiento con Remdesivir. Resultados: La mayoría eran varones, con una edad de 56.5 años (49 años-60.3 años), cuya principal comorbilidad era la obesidad. Los principales síntomas al ingreso fueron disnea y tos. Treinta y dos pacientes recibieron el régimen corto de Remdesivir, 22 fueron cotratados con Baricitinb y 12 con Dexametasona. La mayoría no requirió atención en UCI, 9 pacientes fallecieron, 19% de los cotratados con Baricitinib y 42% de los cotratados con Dexametasona. Se observó una disminución significativa en los niveles de hemoglobina, proteínas, albúmina y LDH. Conclusión: En este estudio observamos una menor mortalidad en los pacientes cotratados con Baricitinib frente a los cotratados con Dexametasona, y una estancia hospitalaria similar a la reportada en estudios clínicos aleatorizados.

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The ubiquity and impact of pharmaceuticals and pesticides, as well as their residues in environmental compartments, particularly in water, have raised human and environmental health concerns. This emphasizes the need of developing sustainable methods for their removal. Solar-driven photocatalytic degradation has emerged as a promising approach for the chemical decontamination of water, sparking intensive scientific research in this field. Advancements in photocatalytic materials have driven the need for solar reactors that efficiently integrate photocatalysts for real-world water treatment. This study reports preliminary results from the development and evaluation of a solar system for TiO2-based photocatalytic degradation of intermittently flowing water contaminated with doxycycline (DXC), sulfamethoxazole (SMX), dexamethasone (DXM), and carbendazim (CBZ). The system consisted of a Fresnel-type UV solar concentrator that focused on the opening and focal point of a parabolic trough concentrator, within which tubular quartz glass reactors were fixed. Concentric springs coated with TiO2, arranged one inside the other, were fixed inside the quartz reactors. The reactors are connected to a raw water tank at the inlet and a check valve at the outlet. Rotating wheels at the collector base enable solar tracking in two axes. The substances (SMX, DXC, and CBZ) were dissolved in dechlorinated tap water at a concentration of 1.0 mg/L, except DXM (0.8 mg/L). The water underwent sequential batch (~ 3 L each, without recirculation) processing with retention times of 15, 30, 60, 90, and 120 min. After 15 min, the degradation rates were as follows: DXC 87%, SMX 35.5%, DXM 32%, and CBZ 31.8%. The system processed 101 L of water daily, simultaneously removing 870, 355, 256, and 318 µg/L of DXC, SMX, DXM, and CBZ, respectively, showcasing its potential for real-world chemical water decontamination application. Further enhancements that enable continuous-flow operation and integrate highly effective adsorbents and photocatalytic materials can significantly enhance system performance.

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The short precorneal residence time of ophthalmic drops is associated with their low absorption; therefore, the development of ocular inserts capable of prolonging and controlling the ophthalmic release of drugs is an interesting option in the design and development of these drugs. A surface response design was developed, specifically the Central Composite Design (CCD), to produce ophthalmic films loaded with Dexamethasone (DEX) by the solvent evaporation method having experimental levels of different concentrations of previously selected polymers (PVP K-30 and Eudragit RS100.). Once optimization of the formulation was obtained, the in vivo test was continued. The optimal formulation obtained a thickness of 0.265 ± 0.095 mm, pH of 7.11 ± 0.04, tensile strength of 15.50 ± 3.94 gF, humidity (%) of 22.54 ± 1.7, mucoadhesion strength of 16.89 ± 3.46 gF, chemical content (%) of 98.19 ± 1.124, release of (%) 13,510.71, and swelling of 0.0403 ± 0.023 g; furthermore, in the in vivo testing the number and residence time of PMN cells were lower compared to the Ophthalmic Drops. The present study confirms the potential use of polymeric systems using PVPK30 and ERS100 as a new strategy of controlled release of ophthalmic drugs by controlling and prolonging the release of DEX at the affected site by decreasing the systemic effects of the drug.

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AIM: The anaesthetic success rate of an inferior alveolar nerve block (IANB) in mandibular molars with irreversible symptomatic pulpitis can be low, and postoperative pain control in teeth with this diagnosis can be challenging. This study aimed to evaluate the influence of preemptive use of dexamethasone and oral potassium diclofenac on the success of IANB. The influence of these drugs on the intensity of postoperative pain was assessed as a secondary outcome. METHODOLOGY: Eighty-four patients with mandibular molars diagnosed with irreversible symptomatic pulpitis recorded preoperative pain intensity using a cold thermal test and a modified Numerical Rating Scale (mNRS). Sixty minutes before the anaesthetic procedure, patients were randomly assigned to one of three groups based on the medication they received: dexamethasone (4 mg), diclofenac potassium (50 mg), or placebo. All patients received IANB with 4% articaine (1:200 000 epinephrine), and 15 min later, they were evaluated for pain intensity using the cold thermal test. Anaesthetic success was analysed. The pain intensity was then recorded, and endodontic treatment and provisional restoration of the tooth were executed in a single session. Patients were monitored for 6, 12, 24, 48 and 72 h using the mNRS to assess the intensity of postoperative pain. RESULTS: There was a statistically significant increase in anaesthetic success when 4 mg dexamethasone (39.3%) or 50 mg diclofenac potassium (21.4%) was used compared to the placebo group (3.6%) (p < .001), with no significant difference between the two drugs. Regarding postoperative pain, dexamethasone was superior to placebo at 6 h (p < .001), with diclofenac having an intermediate behaviour, not differing between dexamethasone and placebo (p > .05). There was no significant difference amongst the groups at 12 h (p > .05). At 24, 48 and 72 h, the effectiveness of dexamethasone and diclofenac were comparable, and both were superior to placebo (p < .001). CONCLUSION: The use of dexamethasone or diclofenac potassium was favourable in terms of increasing the success rate of inferior alveolar nerve block in cases of mandibular molars with irreversible symptomatic pulpitis and decreased the occurrence of postoperative pain when compared to the use of a placebo.

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BACKGROUND: Chikungunya fever is a reemerging epidemic disease caused by a single-stranded RNA alphavirus transmitted throughout by Aedes mosquitoes. Chikungunya virus infection is a biphasic disease in which 72% to 95% of affected individuals manifest acute chikungunya fever. Following the acute phase, more than 40% of affected individuals develop arthritis, often lasting more than 3 months, referred to as chronic chikungunya arthritis, which frequently mimics rheumatoid arthritis. OBJECTIVE: This study aimed to evaluate the efficacy and safety of treatment of chronic chikungunya arthritis with methotrexate and dexamethasone in a randomized, double-blind, placebo-controlled clinical trial. METHODS: The patients were reassessed for treatment response by the DAS28-ESR, tender joint count and swollen joint count, Patient Global Assessment, and for secondary measures, including the Health Assessment Questionnaire Disability Index and Pain Visual Analog Scale. RESULTS: Thirty-one subjects were randomized (placebo, n = 16; methotrexate, n = 15); 27 completed treatment and 4 discontinued during the 8-week blinded period. Among the participants, 96.8% were female, with mean ± SD age was 52.9 ± 13. The mean ± SD disease duration prior to treatment was 220.9 ± 51.2 days. At 8 weeks, methotrexate-treated subjects showed a greater numerical trend towards improvement, but there were no significant differences between methotrexate- dexamethasone group and dexamethasone (placebo) group. CONCLUSION: In this relatively small cohort, all of whom received background dexamethasone, there was a greater numerical improvement trend in prespecified outcome measures, but methotrexate in combination with dexamethasone was not superior to dexamethasone in chronic chikungunya arthritis.

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BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

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Abstract Background and aims: Dexamethasone as adjunct to local anesthetic solution improves the quality of brachial plexus block (BPB). However, evidence for its efficacy at low doses (< 4 mg) is lacking. This study was designed to evaluate the duration of analgesia attained with low dose dexamethasone as adjuvant to local anesthetic for creation of arteriovenous fistula (AVF) under BPB. Methods: Sixty-six patients scheduled for AVF creation were randomly allocated to receive either saline (control) or 2 mg dexamethasone, together with 0.5% ropivacaine and 0.2% lignocaine. The primary outcome was duration of analgesia, defined as time from performing the block to the first analgesic request. The secondary outcomes were time from injection to complete sensory block, time from injection to complete motor block, duration of motor block, postoperative analgesic consumption, and fistula patency at three months. Results: All the blocks were effective. In the group that received dexamethasone, the time to first analgesic request was significantly delayed (432 ± 43.8 minutes vs. 386.4 ± 40.2 minutes; p < 0.01). The onset of sensory and motor blockade occurred faster in dexamethasone group and overall analgesic consumption was also reduced. However, dexamethasone addition did not prolong the duration of motor block. There was no statistically significant difference in the patency of fistulas between the two groups at three months. (p = 0.34). Conclusion: Addition of low-dose perineural dexamethasone to local anesthetic solution significantly prolonged the duration of analgesia. Further trials are warranted to compare the adverse effects between dexamethasone doses of 4 mg and lower.

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