Combination Of Dexamethasone Research Articles

Combination therapy of dexamethasone, rituximab, and cyclosporine for adults with primary immune thrombocytopenia: a prospective observational study

ABSTRACT Background To assess the effectiveness of the combination of dexamethasone, rituximab, and cyclosporine in treating adults with primary immune thrombocytopenia (ITP). Research design and methods This prospective study enrolled consecutive adult patients diagnosed with ITP at the 967th Hospital of the Chinese People’s Liberation Army Joint Service Support Force Hospital between November 2019 and February 2023. Results Twenty-eight patients (13 males, median age 43.5 years) were included. All patients previously experienced ineffective or relapsed ITP, with a median disease duration of 26.5 (range, 7-72) months. At baseline, the median platelet (PLT) count was 13.5 × 109/L (8.25-20 × 109/L). Following treatment, the PLT counts were significantly increased at weeks 1, 3, and 4. The early response rates at weeks 1 and 4 were 82.1% (23/28 patients) and 71.4% (20/28 patients), respectively. The 1-, 3-, and 6-month response rates were 71.4% (20/28), 67.9% (19/28), and 75% (21/28). The treatment-free survival rates at 12 and 24 months were 82.35% (14/17) and 71.43% (10/14), respectively. Six patients experienced transient adverse reactions. Conclusions The combination of dexamethasone, rituximab, and cyclosporine may present a promising therapeutic option for patients with refractory ITP, with good tolerability and mild adverse reactions.

A Comparative Study on the Efficacy of Intravenous Palonosetron Versus a Combination of Ondansetron and Dexamethasone as Prophylaxis for Prevention of Postoperative Nausea and Vomiting After Laparoscopic Surgeries

A Comparative Study on the Efficacy of Intravenous Palonosetron Versus a Combination of Ondansetron and Dexamethasone as Prophylaxis for Prevention of Postoperative Nausea and Vomiting After Laparoscopic Surgeries

Dexamethasone and azithromycin enhance goat sperm preservation quality by regulating lipid metabolism

Phospholipase A (PLA) in goat semen aggregates with egg yolk in semen diluent, leading to sperm death. The aim of this study is to address the issue of sperm death caused by the interaction between PLA and egg yolk, and to explore the protective effect and metabolic regulation mechanism of the combination of dexamethasone (DXMS) and azithromycin (AZM) on goat sperm under low temperature conditions. At a low temperature of 4°C, different concentrations of DXMS were added to semen diluents containing 30μg/mL AZM to detect the quality of goat sperm. The optimal concentration of DXMS was determined to be 20μg/mL. On the 5th day of storage, antioxidant capacity, total cholesterol (TC) levels, energy metabolism, and metabolomics analysis were performed on the sperm of the 20μg/mL DXMS group. The results showed that there was no aggregation caused by the interaction between PLA and egg yolk in the group containing 30μg/mL AZM at 4°C. 20 μg/mL DXMS significantly improved sperm motility, plasma membrane integrity, acrosome integrity, glutathione peroxidase (GPX) (P<0.05), catalase (CAT) (P<0.01), and superoxide dismutase (SOD) activity (P<0.01). The content of reactive oxygen species (ROS) and Fe2+ significantly decreased (P<0.01), while the content of ATP (P<0.01) and TC (P<0.05) significantly increased. Through metabolomics analysis, a total of 56 differential metabolites (P<0.05) were screened, including 5a, 6-Anhydrotetracycline, Betamethasone, and 11-Dehydrocorticosterone, mainly enriched in 8 metabolic pathways (P<0.05), including steroid hormone biosynthesis, glycerophospholipid metabolism, and choline metabolism in cancer. Among them, 5 metabolic pathways are related to lipid metabolism. The results indicate that AZM effectively inhibits the aggregation of PLA and yolk, and the combination of AZM and DXMS enhances the preservation quality of goat sperm during low-temperature preservation by regulating lipid metabolism.

Dexmedetomidine and Dexamethasone as Adjuvants to the Local Anesthetic Mixture in Rhomboid Intercostal and Sub-Serratus Block for Video-Assisted Thoracoscopic Surgery: A Randomized, Double-Blind, Controlled Trial.

The utilization of adjuvants such as dexamethasone and dexmedetomidine in combination with local anesthetics has proven effective in extending analgesia duration. We aimed to investigate the potential efficacy of combining dexmedetomidine and dexamethasone in rhomboid intercostal and sub-serratus (RISS) block for prolonging postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS). We did this randomized, double-blind, controlled trial in two tertiary-care hospitals. A total of eighty-eight patients undergoing VATS under general anesthesia were enrolled in this study. They were randomly assigned into four groups: ropivacaine (R) group, ropivacaine + dexmedetomidine (RM) group, ropivacaine + dexamethasone (RS) group, or ropivacaine + dexmedetomidine + dexamethasone (RSM) group. The primary outcome measure was the duration of analgesia. Secondary outcomes included Numeric Rating Scale (NRS) scores, cumulative oxycodone consumption, and adverse effects. The RSM group exhibited a significantly prolonged duration of analgesia at 1073.5min (932.0-1283.3) compared to the R group with a duration of 154.5min (80.5-199.3) and the RS group with a duration of 282.0min (195.3-350.0, P < 0 0.001). The cumulative oxycodone consumption during the 0-12hours and 0-24-hours period was significantly reduced in the RSM group compared to the R group (P < 0.05). There was also a lower incidence of nausea at 48hours postoperatively in the RSM group compared to the RM group. However, there were no significant differences between the four groups regarding NRS pain scores. The combination of ropivacaine, dexmedetomidine, and dexamethasone in RISS block significantly prolongs the duration of postoperative analgesia following VATS.

The Real-World Outcomes of Relapsed/Refractory Multiple Myeloma Treated with Elotuzumab, Pomalidomide, and Dexamethasone.

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed the efficacy and safety of EPd in a real-world cohort of RRMM patients. Patients and Methods: The medical records of 22 patients who received EPd for RRMM at Yokohama Municipal Citizen's Hospital (Japan) between January 2020 and July 2021 were reviewed. Results: The median age of our cohort was 73.5 years. The overall response rate was 55%. With a median follow-up of 20.2 months, the median progression-free survival (PFS) was 9.1 months (95% confidence interval [CI], 2.5-23.0 months). The median PFS was shorter in patients with a poor performance status (PS) than in those with favorable PS (2.5 vs. 10.8 months; p < 0.01). Patients with prior daratumumab had significantly shorter PFS than those without prior daratumumab (2.1 vs. 23.0 months; p < 0.01). Additionally, patients with prior pomalidomide had significantly shorter PFS (1.7 vs. 10.3 months; p < 0.01). In the multivariate analysis, poor PS (hazard ratio [HR] = 4.1, 95% CI: 1.1-15.6; p = 0.04) and prior exposure to daratumumab (HR = 3.8, 95% CI: 1.1-13.8; p = 0.04) remained significantly associated with shorter PFS. Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore, EPd may be useful, especially in daratumumab-naïve patients.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema-A Swiss Cohort Study.

Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5-166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 μm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

Comparison of ropivacaine with ropivacaine–dexamethasone combination for postoperative analgesia in the pectoral nerve block for modified radical mastectomy: A randomized clinical trial

Abstract Background and Aims: The pectoral nerve block types I and II are novel techniques to provide analgesia for modified radical mastectomy (MRM) surgeries performed under general anesthesia. The primary objective of this study was to compare the duration of effective analgesia, and the secondary objectives were to evaluate the total amount of rescue analgesics in 24 h, hemodynamic changes, and postoperative adverse effects. Methods: This prospective, randomized, double-blind study was conducted on a total of 80 women with breast cancer belonging to American Society of Anesthesiologist class I and II scheduled for MRM, which were randomly allocated into two groups – Group R (n = 40) received 0.25% ropivacaine 29 ml + NS 1 ml and Group RD (n = 40) received 0.25% ropivacaine 29 ml + dexamethasone (4 mg) 1 ml. Ten milliliters of the study drug was used in Pecs I and the rest 20 ml in Pecs II block posttumor resection. Results: The duration of analgesia was statistically significantly longer in RD (778.75 ± 55.12 min) compared to Group R (412.63 ± 21.69 min) (P &lt; 0.05). Pain scores were significantly less in Group RD. The mean dose of acetaminophen required was significantly less in Group RD (2362.50 ± 375.32 mg) than in Group R (3525.00 ± 298.50 mg) (P &lt; 0.05). The incidence of adverse events was similar in both groups. Conclusion: The addition of dexamethasone with ropivacaine in the Pecs block can be used for prolonging the effective duration of analgesia and decreasing postoperative analgesic consumption with comparable hemodynamic and side effect profiles.

Integrated Multi-Omics Analysis Reveals Mountain-Cultivated Ginseng Ameliorates Cold-Stimulated Steroid-Resistant Asthma by Regulating Interactions among Microbiota, Genes, and Metabolites.

Steroid-resistant asthma (SRA), resisting glucocorticoids such as dexamethasone (DEX), is a bottleneck in the treatment of asthma. It is characterized by a predominantly neutrophilic inflammatory subtype and is prone to developing into severe refractory asthma and fatal asthma. Currently, there is a lack of universally effective treatments for SRA. Moreover, since cold stimulation does increase the risk of asthma development and exacerbate asthma symptoms, the treatment of cold-stimulated SRA (CSRA) will face greater challenges. To find effective new methods to ameliorate CSRA, this study established a CSRA mouse model of allergic airway inflammation mimicking human asthma for the first time and evaluated the alleviating effects of 80% ethanol extract of mountain-cultivated ginseng (MCG) based on multi-omics analysis. The results indicate that cold stimulation indeed exacerbated the SRA-related symptoms in mice; the DEX individual treatment did not show a satisfactory effect; while the combination treatment of DEX and MCG could dose-dependently significantly enhance the lung function; reduce neutrophil aggregation; decrease the levels of LPS, IFN-γ, IL-1β, CXCL8, and IL-17; increase the level of IL-10; alleviate the inflammatory infiltration; and decrease the mucus secretion and the expression of MUC5AC. Moreover, the combination of DEX and high-dose (200 mg/kg) MCG could significantly increase the levels of tight junction proteins (TJs), regulate the disordered intestinal flora, increase the content of short-chain fatty acids (SCFAs), and regulate the abnormal gene profile and metabolic profile. Multi-omics integrated analysis showed that 7 gut microbes, 34 genes, 6 metabolites, and the involved 15 metabolic/signaling pathways were closely related to the pharmacological effects of combination therapy. In conclusion, integrated multi-omics profiling highlighted the benefits of MCG for CSRA mice by modulating the interactions of microbiota, genes, and metabolites. MCG shows great potential as a functional food in the adjuvant treatment of CSRA.

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma: A Western perspective.

Post-embolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Many strategies have been evaluated to reduce the incidence of PES, but no standard prevention guidelines currently exist. In a single-center, placebo-controlled trial, Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES (from 80% to 6%), of post-procedural liver decompensation (from 14% to 0%), and a shorter hospital stay (4 days vs 6 days), alongside an acceptable safety profile. The results of this study raise several controversial points regarding their applicability in the Western world. In the West, there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis, so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis. Furthermore, in the West, there is a preferred use of drug-eluting beads loaded with doxorubicin, which are associated with a lower incidence of PES. A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

Dexamethasone reduces cisplatin-induced hair cell damage by inducing cisplatin resistance through metallothionein-2.

Hair cell damage is a common side effect caused by the anticancer drug cisplatin (CDDP), which reduces patient quality of life. One CDDP resistance mechanism that occurs in recurrent cancers is heavy metal detoxification by metallothionein-2 (mt2). Here, we show that in zebrafish larvae, dexamethasone (DEX) reduces CDDP-induced hair cell damage by enhancing mt2 expression. Transgenic zebrafish (cldn: gfp; atoh1: rfp) that express green and red fluorescent proteins in neuromasts and hair cells, respectively, were used. The zebrafish were pretreated with DEX at 52h post-fertilization (hpf) for 8h, followed by CDDP treatment for 12h. The lateral line hair cells of CDDP-treated zebrafish at 72hpf were observed by fluorescence microscopy. Reporting odds ratio (ROR) analysis using an adverse event database indicated an association between a decrease in CDDP-induced ototoxicity and DEX as an antiemetic treatment for cancer chemotherapy. Pretreatment with DEX protected 72hpf zebrafish hair cells from CDDP-induced damage. The expression of mt2 mRNA was significantly increased by the combination of 10µM DEX with CDDP. Gene editing of mt2 reversed the protective effect of DEX against CDDP-induced damage in hair cells. DEX protects hair cells from CDDP-induced damage through increased mt2 expression, which is a resistance mechanism for platinum-based anticancer drugs.

Chemotherapy-Induced Peripheral Neuropathy Impacts Quality of Life and Activities of Daily Living of Brazilian Multiple Myeloma Patients.

Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapyinduced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health- Related Quality of Life (HRQoL) and activities of daily living (ADL). We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

MAP3K8 is a potential therapeutic target in airway epithelial inflammation

BackgroundWe have previously discovered clusters of sequentially negative and positive modulators of acute inflammation during cytokine stimulation in epithelial cells and identified potential targets for therapy within these clusters. MAP3K8 is a druggable kinase that we found to be a hub of a principal interaction network. We describe here the results of MAP3K8 knockdown in the A549 lung cancer cell line, the BEAS-2B epithelial cell line and normal human bronchial epithelial (NHBE) cells following IL-1β stimulation. We analysed signalling transduction and global gene expression after IL-1β stimulation with and without MAP3K8 knockdown, quantifying levels of the inflammatory cytokines IL-6, IL-8 and RANTES levels by qPCRs and/or by ELISAs. We also examined potential small molecule inhibitors for MAP3K8 in the same models.ResultsIL-1β significantly and consistently increased MAP3K8 expression after 2 h in A549, BEAS-2B and NHBE cells. Phosphorylation of MAP3K8 occurred at 20 min after IL-1β stimulation and MAP3K8 protein was degraded at 30 min. MAP3K8 knockdown significantly reduced IL-6, IL-8 levels after IL-1β stimulation and yielded a 10-fold enhancement of the anti-inflammatory effects of dexamethasone. Phosphorylation of ERK1/2 (P-ERK1/2) and phosphorylation of SAPK/JNK (P-SAPK/JNK) decreased at 30 min after IL-1β stimulation with MAP3K8 knockdown. The combination of dexamethasone and MAP3K8 knockdown resulted in greater inhibition of phosphorylated ERK1/2 and SAPK/JNK. Nineteen genes including MMP1, MMP3, MMP10, ITGB8, LAMC2 and PLAT (P corrected < 0.01 respectively) demonstrated a distinct altered temporal response to IL-1β following suppression of MAP3K8. However, putative MAP3K8 inhibitors including Tpl2-1, Tpl2-2 and GSK2222867A only showed inhibition of IL-6 and IL-8 production at a high dose.ConclusionsThese results confirm that MAP3K8 is a key mediator of the early inflammatory response and that it is a potential target in inflammatory diseases. However, current tool compounds do not effectively inhibit its effects.

Comparison of Dexamethasone-Denenhydraminate and Dexamethasone-Ondansetron in Preventing Post-Operative Nausea and Vomiting after Laparoscopic Cholecystectomy

Introduction: Postoperative nausea and vomiting (PONV) is one of the most common problems after implementation of general anesthesia. Laparoscopic cholecystectomy for the treatment of cholelithiasis is popular amongst surgeons as well as patients due to its associated advantages, which includes a short hospital stay. However high incidences of PONV have been reported after laparoscopic cholecystectomy. Objective: To compare the efficacy of combination dexamethasone-dimtenhydrinate with dexa-methasone-ondansetron in preventing postoperative nausea and vomiting after laparoscopic cholecystectomy. Study design: Randomized controlled trial Settings: Department of Anaesthesia, Holy Family Hospital, Rawalpindi Medical University and Allied Hospital. Duration of study: Study was carried out over a period of six months from 01-01-2022 to 30-06-2022. Methodology: A total of 160 patients were enrolled, 80 patients each to either group D for Dexamethasone-Dimenhydrinate group or group-O for Dexamethasone-Ondansetron. Results: Mean age of the patients was 42.3±13.2 and 42.4±14.0 in group-D and Group-O, respectively. There were 40 (50%) males and females in group-D while 29 males (36.3%) and 51 females (63.7%) in group-O. Efficacy of combination dexamethasone+ dimtenhydrinate with dexamethasone+ondansetron in preventing PONV showed at 30 minutes (5.0% vs 12.5%; p=0.093), at 60 minutes (7.5% vs 20.0%; p=0.022), at 120 minutes (6.3% vs 17.5%; p=0.028) and at 24 hours (5.0% vs 18.8%; p=0.007). Conclusion: In conclusion, our study demonstrated that dexamethasone–dimenhydrinate combination was more effective than dexamethasone–ondansetron combination in prevention of nausea and vomiting after laparoscopic cholecystectomy.

An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly diagnosed POEMS syndrome.

This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.

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

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

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow-up of a multicenter, retrospective real-world experience with 321 cases outside of controlled clinical trials.

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab.

Study on the mechanism of glucocorticoid receptor mitochondrial translocation and glucocorticoid-induced apoptosis in macrophages

Objective 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. Methods 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. Results 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. Conclusions 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.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Extramedullary Intracranial Plasmacytomas: A Systematic Review of Literature.

Extramedullary plasmacytoma (EMP) is an uncommon disorder characterized by the development of abnormal plasma cell tumors outside the bone marrow. These tumors are typically observed in various locations, including the upper respiratory tract, gastrointestinal tract, and other soft tissues. Among the less explored manifestations of EMP is intracranial EMP, which remains poorly understood due to the limited literature available on the subject. The objective was to comprehend the population characteristics, localization, type, treatment, and outcomes of intracranial EMP. A systematic review of the literature for EMPs was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The strategy "extramedullary plasmacytoma AND multiple myeloma" was used for the search. The search terms were queried using PubMed, Embase, Scopus, Cochrane, and Web of Science databases. We included only those studies that presented clinical studies with patients diagnosed with intracranial plasmacytomas. In this study, a total of 84 patients from 25 studies were analyzed. The average age of diagnosis was 57.25 years, with a slightly higher proportion of females (57%) compared to male patients (43%). The most common locations of intracranial plasmacytomas were the clivus (29.7%), frontal lobe (18.9%), parietal lobe (8.1%), occipital lobe (6.7%), temporal lobe (6.7%), and sphenoid (4%). Chordoma and meningioma were the most common differential diagnoses encountered during clinical investigations. Treatment modalities included radiotherapy (RT), chemotherapy (QT), surgical resection (SR), and conservative approaches. The most frequent treatment combinations were SR + RT (19%) and RT only (17.8%). Mortality was reported in 48% of the cases, with complete resolution observed in 10 cases and partial resolution in 3 cases. The average follow-up duration was 37.5 months. The clivus is the most frequently reported site of extramedullary intracranial plasmacytoma (EMIP) occurrence, representing 29.7% of cases. Chordomas were commonly observed alongside EMIPs and emerged as the primary differential diagnosis. RT was the predominant treatment modality, with SR considered when feasible. RT alone demonstrated the highest effectiveness in managing EMIPs (30%), while QT as a sole intervention showed lower efficacy. However, a combination of dexamethasone, lenalidomide, and targeted RT displayed promising results, offering improved tumor response and increased safety.

Transzonular moxifloxacin and dexamethasone delivery in phacoemulsification: A novel dropless regimen.

To assess the safety and efficacy of transzonular moxifloxacin and dexamethasone versus standard postoperative topical drug regimen in phacoemulsification. Nonrandomized prospective study. The study included 100 eyes of 100 age and gender-matched individuals with senile cataract undergoing routine phacoemulsification. The patients were consecutively divided into transzonular (TZ = 50) and topical (TP = 50) groups. Both the groups were followed up for 4 weeks and assessed for intraocular inflammation, visual acuity, changes in intraocular pressure (IOP), and any adverse events. The grades of inflammation were significantly lower in TZ as compared to the TP group ( P < 0.001). The IOP remained normal and comparable in both the groups. Most of the patients in the two groups attained a visual acuity of 0.2 or better at the end of the follow-up. No adverse effects and increased rate of endophthalmitis were noted in TZ group. A one-time peroperative TZ moxifloxacin and dexamethasone combination is a safe and effective method to control postoperative inflammation after cataract surgery. A word of caution though, due precautions to be exercised to prevent the risk of inflammation and endophthalmitis.