Alleviating iatrogenic effects of paclitaxel via antiinflammatory treatment.

BACKGROUND: Paclitaxel (PTX) is touted as an essential medicine due to its extensive use as a chemotherapeutic agent for various cancers and an antiproliferative agent for endovascular applications. Emerging studies in cardio-oncology implicate various vascular complications of chemotherapeutic agents. METHODS: We evaluated the inflammatory response induced by the systemic administration of PTX. The investigation included RNAseq analysis of primary human endothelial cells (ECs) treated with PTX to identify transcriptional changes in pro-inflammatory mediators. Additionally, we used dexamethasone (DEX), a well-known antiinflammatory compound, to assess its effectiveness in counteracting these PTX-induced changes. Further, we studied the effects of PTX on monocyte chemoattractant protein-1 (MCP-1) levels in the media of ECs. The study also extended to in vivo analysis, where a group of mice was injected with PTX and subsequently harvested at different times to assess the immediate and delayed effects of PTX on inflammatory mediators in blood and aortic ECs. RESULTS: Our RNAseq analysis revealed that PTX treatment led to significant transcriptional perturbations in pro-inflammatory mediators such as MCP-1 and CD137 within primary human ECs. These changes were effectively abrogated when DEX was administered. In vitro experiments showed a marked increase in MCP-1 levels in EC media following PTX treatment, which returned to baseline upon treatment with DEX. In vivo, we observed a threefold increase in MCP-1 levels in blood and aortic ECs 12 h post-PTX administration. Similar trends were noted for CD137 and other downstream mediators like tissue factor, vascular cell adhesion molecule 1, and E-selectin in aortic ECs. CONCLUSION: Our findings illustrate that PTX exposure induces an upregulation of atherothrombotic mediators, which can be alleviated with concurrent administration of DEX. Considering these observations, further long-term investigations should focus on understanding the systemic implications associated with PTX-based therapies and explore the clinical relevance of DEX in mitigating such risks.

ECM1 and KRT6A are involved in tumor progression and chemoresistance in the effect of dexamethasone on pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Neoadjuvant chemotherapy is an effective PDAC treatment option, but chemotherapy causes unfavorable side effects. Glucocorticoids (e.g., dexamethasone [DEX]) are administered to reduce side effects of chemotherapy for solid tumors, including pancreatic cancer. Glucocorticoids have both beneficial and detrimental effects, however. We investigated the functional changes and gene-expression profile alterations induced by DEX in PDAC cells. PDAC cells were treated with DEX, and the cell proliferation, migration, invasion, and chemosensitivity to gemcitabine (GEM) were evaluated. The results demonstrated decreased cell proliferative capacity, increased cell migration and invasion, and decreased sensitivity to GEM. A comprehensive genetic analysis revealed marked increases in ECM1 and KRT6A in DEX-treated PDAC cells. We evaluated the effects of ECM1 and KRT6A expression by using PDAC cells transfected with those genes. Neither ECM1 nor KRT6A changed the cells' proliferation, but each enhanced cell migration and invasion. ECM1 decreased sensitivity to GEM. We also assessed the clinicopathological significance of the expressions of ECM1 and KRT6A in 130 cases of PDAC. An immunohistochemical analysis showed that KRT6A expression dominated the poorly differentiated areas. High expressions of these two proteins in PDAC were associated with a poorer prognosis. Our results thus demonstrated that DEX treatment changed PDAC cells' functions, resulting in decreased cell proliferation, increased cell migration and invasion, and decreased sensitivity to GEM. The molecular mechanisms of these changes involve ECM1 and KRT6A, whose expressions are induced by DEX.

Supramolecular Hydrogel Dexamethasone-Diclofenac for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) severely affects patients' quality of life and is commonly treated with glucocorticosteroids injections, like dexamethasone, which may have side effects. This study aimed to create a novel low dose of twin-drug hydrogel containing dexamethasone and diclofenac and explore its potential as a drug delivery system for an enhanced anti-inflammatory effect. Its characterization involved rheology, transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Furthermore, the hydrogel demonstrated thixotropic properties. The hydrogel exhibited no cytotoxicity against RAW 264.7 macrophages. Furthermore, the hydrogel demonstrated a significant anti-inflammatory efficacy by effectively downregulating the levels of NO, TNF-α, and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The co-delivery approach, when intra-articularly injected in adjuvant-induced arthritis (AIA) rats, significantly alleviated chronic inflammation leading to reduced synovitis, delayed bone erosion onset, and the downregulation of inflammatory cytokines. The biocompatibility and adverse effect evaluation indicated good biological safety. Furthermore, the hydrogel demonstrated efficacy in reducing NF-κB nuclear translocation in LPS-induced RAW 264.7 macrophages and inhibited p-NF-kB, COX-2, and iNOS expression both in RAW 264.7 macrophages and the joints of AIA rats. In conclusion, the findings indicate that the hydrogel possesses potent anti-inflammatory activity, which effectively addresses the limitations associated with free forms. It presents a promising therapeutic strategy for the management of RA.

Effects of Dexamethasone on Postoperative Glycemic Control in Patients After Primary Total Joint Arthroplasty: A Randomized Double-Blind Controlled Trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the use of dexamethasone (DEX) may cause perioperative blood glucose (BG) disorders, leading to complications even in patients who do not have diabetes. We aimed to evaluate the effects of different DEX doses on perioperative BG levels. METHODS: A total of 135 patients who do not have diabetes were randomized into three groups: preoperative intravenous injection of normal saline (Group A, the placebo group), preoperative intravenous injection of 10 mg DEX (Group B), and preoperative intravenous injection of 20 mg DEX (Group C). Postoperative fasting blood glucose (FBG) levels were designated as the primary outcome, while postoperative postprandial blood glucose (PBG) levels were assigned as the secondary outcome. The incidence of complications was recorded. We also investigated the risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. RESULTS: The FBG levels were higher in Groups B and C than in Group A on postoperative days (POD) 0 and 1. The PBG levels were lower for Groups A and B compared to Group C on POD 1. No differences in FBG or PBG were detected beyond POD 1. Elevated preoperative glycosylated hemoglobin A1c (HbA1c) levels increased the risk of FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl, respectively. However, preoperative intravenous injection of DEX was not associated with FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. No differences were found in postoperative complications among the three groups. CONCLUSION: The preoperative intravenous administration of 10 or 20 mg DEX in patients who do not have diabetes showed transient effects on postoperative BG after TJA. The preoperative HbA1c level threshold (regardless of the administration or dosage of DEX) that increased the risk for the occurrence of FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl was 5.75% and 5.85%, respectively.

Dexamethasone in Patients with Glioblastoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Glioblastomas are the most common primary central nervous system (CNS) tumors. Although modern management strategies have modestly improved overall survival, the prognosis remains dismal, with treatment side effects often impinging on the clinical course. Glioblastomas cause neurological dysfunction by infiltrating CNS tissue and via perifocal oedema formation. The administration of steroids such as dexamethasone is thought to alleviate symptoms by reducing oedema. However, despite its widespread use, the evidence for the administration of dexamethasone is limited and conflicting. Therefore, we aimed to review the current evidence concerning the use and outcomes of dexamethasone in patients with glioblastoma. METHODS: We performed a systematic review and meta-analysis according to the PRISMA-P guidelines. We performed a restricted search using the keywords "Dexamethasone" and "Glioblastoma" on PubMed, Web of Science, Cochrane Library, and Academic Search Premier. We included studies reporting on overall survival (OS) and progression-free survival (PFS) in glioblastoma patients receiving higher or lower dexamethasone doses. The risk of bias was assessed using ROBINS-I. We performed a meta-analysis using a random effects model for OS and PFS. RESULTS: Twenty-two retrospective studies were included. Higher doses of dexamethasone were associated with poorer OS (hazard ratio 1.62, confidence interval 1.40-1.88) and PFS (1.49, 1.23-1.81). OS remained worse even when studies corrected for clinical status (1.52, 1.38-1.67). CONCLUSION: Despite the widespread use of dexamethasone in glioblastoma patients, its use is correlated with worse long-term outcomes. Consequently, Dexamethasone administration should be restricted to selected symptomatic patients. Future prospective studies are crucial to confirm these findings.

Intravenous injection of dexamethasone is non-inferior to perineural administration for popliteal sciatic nerve and saphenous nerve blocks: A randomized, controlled, triple-blind study.

Background: The aim of this study was to assess whether intravenous dexamethasone was noninferior to perineural dexamethasone as an adjuvant to ropivacaine for a combination of saphenous and sciatic nerve blocks in patients undergoing foot and ankle surgery. Methods: This was a prospective, blinded, randomized noninferiority study. Seventy-five patients, aged 18-75 years, with an American Society of Anesthesiologists (ASA) physical status I-III who underwent foot and ankle surgery were involved. Patients scheduled for ultrasound-guided popliteal sciatic nerve block and saphenous nerve block were randomized to receive 0.375% ropivacaine with 7.5 mg of dexamethasone perineurally (Dex-PN), 10 mg of dexamethasone intravenously (Dex-IV) or neither (Placebo). The primary outcome was the duration of analgesia. The major secondary outcomes were the composite pain intensity and opioid consumption score at 0-48 h intervals after anesthesia. Results: The mean analgesic duration was 26.2 h in the Dex-IV group and 27.9 h in the Dex-PN group (duration difference, -1.7; 95% CI, -3.8 to 0.43; P = 0.117), and both durations were significantly longer than that in the placebo group (17.6 h, P < 0.001). Conditions for establishing non-inferiority were met. Conclusions: Our findings indicate that a single 10-mg intravenous dose of dexamethasone was noninferior to the combined dose of ropivacaine plus deaxmethasone in terms of duration of analgesia for foot and ankle surgery.

Honokiol induces apoptosis and autophagy in dexamethasone-resistant T-acute lymphoblastic leukemia CEM-C1 cells.

Objective: To study whether and, if so, how honokiol overcome dexamethasone resistance in DEX-resistant CEM-C1 cells. Methods: We investigated the effect of honokiol (0-20 µM) on cell proliferation, cell cycle, cell apoptosis and autophagy in DEX-resistant CEM-C1 cells and DEX-sensitive CEM-C7 cells. We also determined the role of c-Myc protein and mRNA in the occurrence of T-ALL associated dexamethasone resistance western blot and reverse transcription-qPCR (RT-qPCR) analysis. Results: Cell Counting Kit (CCK)-8 assay shows that DEX-resistant CEM-C1 cell lines were highly resistant to dexamethasone with IC50 of 364.1 ± 29.5 µM for 48 h treatment. However, upon treatment with dexamethasone in combination with 1.5 µM of honokiol for 48 h, the IC50 of CEM-C1 cells significantly decreased to 126.2 ± 12.3 µM, and the reversal fold was 2.88. Conversely, the IC50 of CEM-C7 cells was not changed combination of dexamethasone and honokiol as compared to that of CEM-C7 cells treated with dexamethasone alone. It has been shown that honokiol induced T-ALL cell growth inhibition by apoptosis and autophagy via downregulating cell cycle-regulated proteins (Cyclin E, CDK4, and Cyclin D1) and anti-apoptotic proteins BCL-2 and upregulating pro-apoptotic proteins Bax and led to PARP cleavage. Honokiol may overcome dexamethasone resistance in DEX-resistant CEM-C1 cell lines via the suppression of c-Myc mRNA expression. Conclusion: The combination of honokiol and DEX were better than DEX alone in DEX-resistant CEM-C1 cell lines. Honokiol may regulate T-ALL-related dexamethasone resistance by affecting c-Myc.

Lactobacillus gasseri BNR17 Ameliorates Dexamethasone-Induced Muscle Loss in BALB/c Mice and C2C12 Myotubes.

This study aimed to investigate the effects and mechanism of Lactobacillus gasseri BNR17, a probiotic strain isolated from human breast milk, on dexamethasone-induced muscle loss in mice and cultured myotubes. BALB/c mice were intraperitoneally injected with dexamethasone, and orally administered L. gasseri BNR17 for 21 days. L. gasseri BNR17 treatment ameliorated dexamethasone-induced decline in muscle function, as evidenced by an increase in forelimb grip strength, treadmill running time, and rotarod retention time in both female and male mice. In addition, L. gasseri BNR17 treatment significantly increased the mass of the gastrocnemius and quadriceps muscles. Dual-energy X-ray absorptiometry showed a significant increase in lean body mass and a decrease in fat mass in both whole body and hind limb after treatment with L. gasseri BNR17. It was found that L. gasseri BNR17 treatment downregulated serum myostatin level and the protein degradation pathway composed of muscle-specific ubiquitin E3 ligases, MuRF1 and MAFbx, and their transcription factor FoxO3. In contrast, L. gasseri BNR17 treatment upregulated serum insulin-like growth factor-1 level and Akt-mTOR-p70S6K signaling pathway involved in protein synthesis in muscle. As a result, L. gasseri BNR17 treatment significantly increased the levels of major muscular proteins such as myosin heavy chain and myoblast determination protein 1. Consistent with in vivo results, L. gasseri BNR17 culture supernatant significantly ameliorated dexamethasone-induced C2C12 myotube atrophy in vitro. In conclusion, L. gasseri BNR17 ameliorates muscle loss by downregulating the protein degradation pathway and upregulating the protein synthesis pathway.

Changes in intraocular pressure following intravitreal dexamethasone implant in patients with history of glaucoma filtration surgery.

PURPOSE: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery. METHODS: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure. RESULTS: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%). CONCLUSION: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma.

ESASO classification relevance in the diagnosis and evolution in diabetic macular edema patients after dexamethasone implant treatment.

PURPOSE: To assess the clinical relevance of The European School for Advanced Studies in Ophthalmology (ESASO) classification in patients with diabetic macular edema (DME) after their first dexamethasone implant (DEXI) treatment. METHODS: Retrospective real-world study conducted on consecutive DME patients who underwent DEXI treatment and were controlled at month-2. Subjects were initially classified according to the ESASO classification stages. The outcomes were anatomical biomarkers with spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA). RESULTS: A total of 128 patients were classified according to ESASO classification stages as early (7; 5.5%), advanced (100; 78.1%), and severe (21; 16.4%). At baseline, there were significant differences between stages in BCVA, central macular thickness (CMT), and tomography anatomical biomarkers (p < 0.05). Initial BCVA (logMAR) was 0.33 ± 0.10, 0.58 ± 0.34, and 0.71 ± 0.35 in the early, advanced, and severe stages, respectively (p < 0.05). At month-2, BCVA was 0.17 ± 0.15, 0.46 ± 0.29, and 0.69 ± 0.27 in those classified as early, advanced, and severe stages, respectively. At month-2, DME was resolved or improved in 6 (85.7%), 60 (60%), and 12 (60%) patients classified as early, advanced, and severe stages, respectively. CONCLUSIONS: There was a good correlation between BCVA and ESASO classification stages. Patients in the severe stage did not achieve visual acuity improvement over the study period.

A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.

INTRODUCTION: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1. OBJECTIVES AND METHODS: We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. RESULTS: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high-risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)-exposed (including both Len-sensitive and Len-refractory pts), and 22% were Len-refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non-hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1-2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow-up of 38 m, median PFS (mPFS) was 16 m and the 1-year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len-naïve (NR), age ≥70 (20 m). In pts exposed to Len, non-refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len-refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). CONCLUSION: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len-sensitive, independent of age, and cytogenetic risk.

The Effect of Dexamethasone on Neuroinflammation and Cerebral Edema in Rats With Traumatic Brain Injury Combined With Seawater Drowning.

OBJECTIVE: To investigate the effect and mechanism of dexamethasone (DX) on axonal injury after traumatic brain injury (TBI) combined with seawater drowning (SWD) in rats. METHODS: To gain an in-depth understanding of TBI + SWD in rats, we established the compound injury model of rats by the Marmarou method and intratracheal pumping of seawater to simulate the pathological conditions. Rats in the DX group received intraperitoneal injections of DX (1 mg/kg) immediately after injury, and rats in the sham group and TBI + SWD group received intraperitoneal injections of the same amount of normal saline. RESULTS: Hematoxylin-eosin (HE) showed that DX improved matrix looseness, cell swelling, and nuclear condensation 168 hours after injury. Immunohistochemistry (IHC) staining showed that the protein expression of AQP4 was decreased in the DX group compared with the TBI + SWD group from 12 hours to 168 hours after injury. DX decreased the modified neurological severity score (mNSS) significantly at 24 hours and 168 hours after injury (P < 0.05). At 72 h and 168 h after injury, DX significantly lowered the expressions of IL-8 and TNF-α (P < 0.05). CONCLUSION: DX may play a neuroprotective role by reducing cerebral edema and inflammatory response after TBI + SWD injury in rats.

Use of Dexamethasone for Severe Fatigue in the Advanced Cancer Population: A Brief Report.

Background: Fatigue is a common and distressing symptom for palliative care patients. Although the current literature emphasizes nonpharmacological management, dexamethasone is reportedly used in clinical practice. This study helps to characterize its use, efficacy, and adverse effects in a real-world setting. Objective: To improve the evidence base by exploring the use, efficacy, and side effect profile of dexamethasone for fatigue management. Methods: This international multisite prospective observational case series assessed the benefit and adverse effects of dexamethasone at baseline (T0) and at five to seven days postbaseline (T1). Fatigue scores were assessed using the symptom assessment scale (SAS) and visual analogue fatigue scale (VAFS). Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). The related samples Wilcoxon signed-rank test was used to compare before and after scores. Results: All 18 patients (male-female, 11:7) had advanced metastatic cancer with most in the deteriorating palliative care phase (56%). The most common dose of dexamethasone was 4 mg daily orally. At T1 (n = 12), improvement was seen in all measures of fatigue; the median SAS scores decreased from 7 to 5.5 (p = 0.007), the median VAFS scores increased from 3 to 5 (p = 0.126), and the median NCI-CTCAE fatigue scores were reduced from 3 to 2.5 (p = 0.18). Dexamethasone was well tolerated; one participant experienced grade 3 delirium. Conclusion: The small number of participants recruited for this study suggests that dexamethasone is not widely used specifically for fatigue. Our results suggest an improvement in fatigue scores from T0 to T1.

Perioperative Intravenous Dexamethasone Use Is Not Associated with Periprosthetic Joint Infection or Wound Healing Complications Following Shoulder Arthroplasty.

BACKGROUND: Perioperative intravenous (IV) dexamethasone is commonly used in lower extremity total joint arthroplasty to manage postoperative pain and nausea/vomiting, and recent studies have demonstrated that its use may lower rates of acute postoperative medical complications. However, there is limited information regarding the safety and efficacy of IV dexamethasone in patients undergoing total shoulder arthroplasty (TSA). Additionally, there is concern surrounding corticosteroid use prior to surgery as preoperative corticosteroid injections have been associated with adverse outcomes after TSA, including periprosthetic joint infection (PJI) and revision surgery. Thus, the purpose of this study was to evaluate the effect of perioperative IV dexamethasone on 90-day rates of PJI, wound complications, and medical complications after TSA. METHODS: The Premiere national hospital database was used to identify adult patients undergoing elective TSA between 2016 and 2020; patients were excluded if they were under 18 years old, were undergoing revision TSA, or had a prior proximal humerus open reduction internal fixation (ORIF) procedure. Patients who did and did not receive perioperative IV dexamethasone were then compared in both univariate and multivariate analyses. A Bonferroni correction was utilized to adjust for multiple comparisons. The primary endpoint was risk of acute infectious complications within 90 days of surgery, including PJI and wound infection/dehiscence. Secondary endpoints included acute pulmonary, renal, and thromboembolic complications. RESULTS: A total of 135,333 patients underwent TSA during the study period; 61.2% underwent reverse total shoulder arthroplasty (RTSA), 33.8% underwent anatomic total shoulder arthroplasty (ATSA), and 5.0% underwent hemiarthroplasty (HA). From 2016 to 2020, perioperative IV dexamethasone use increased by 135%. Multivariate analysis revealed that patients who received perioperative IV dexamethasone did not have increased odds of PJI, superficial wound infection, or wound dehiscence (p = 0.15 - 0.47) but did have decreased odds of sepsis (OR 0.67, 95% CI 0.55-0.81) and other medical complications such as urinary tract infection (UTI) and acute kidney injury (AKI). Additionally, there was a trend towards decreased 90-day hospital readmission (OR 0.88, 95% CI 0.81-0.96, p=0.003). CONCLUSIONS: Perioperative IV dexamethasone was not associated with increased risk of acute infectious and wound healing complications. Moreover, patients who received perioperative IV dexamethasone had decreased odds of medical complications and trended towards lower rates of 90-day hospital readmission. The results of this study support the safety of perioperative IV dexamethasone use in patients undergoing elective TSA.

Comparative Efficacy of High-Dose Dexamethasone Versus Methylprednisolone in Coronavirus Disease 2019 (COVID-19)-Associated Acute Respiratory Distress Syndrome.

OBJECTIVE: This retrospective (matched paired) clinical trial aimed to compare the efficacy of dexamethasone vs. methylprednisolone at equipotent (high) doses in patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). METHODS: A total of 347 patients with moderate and severe COVID-19-associated ARDS were administered either a high (equipotent) dose of dexamethasone (32 mg) or methylprednisolone (180 mg) for a duration of up to 10 days. All participants received the standard of care for critically ill COVID-19 patients. RESULTS: The primary outcomes included length of stay in the ICU, ICU mortality, and discharge from the hospital. Based on the obtained results, a tendency towards more favorable clinical outcomes concerning the length of stay in the ICU (in the group of patients treated with non-invasive mechanical ventilation (NIV), p<0.05), ICU mortality, and discharge from the hospital (in the group of patients who were intubated, p<0.05) in patients receiving the high dose of dexamethasone compared to those receiving methylprednisolone was observed. CONCLUSION: It appears that severe cases of COVID-19, especially intubated ones, treated with high doses of dexamethasone have a more favorable clinical outcome than the use of equipotent doses of methylprednisolone. However, larger multicenter studies are needed to validate our observations.

Moderate Intra-Abdominal Pressure Levels in Robot-Assisted Radical Prostatectomy Seem to Have No Negative Impact on Clinical Outcomes.

Introduction: Radical prostatectomy is increasingly performed laparoscopically with robot assistance (RALRP). RALRP, as with all laparoscopic procedures, requires a pneumoperitoneum, which might result in peritoneal inflammatory response reactions and postoperative pain. The aim of this retrospective single-centre study was to analyse the effects of a pneumoperitoneum during RARLP on clinical outcomes. Methods: All patients who underwent robot-guided prostatectomy in our clinic were included, with the exception of patients who were converted to open prostatectomy. C-reactive protein was used as a marker for the primary outcome, namely the postoperative inflammatory response. Intra-abdominal pressure (IAP) was evaluated as a potential factor influencing inflammation. In addition, the waist-hip ratio was used to estimate the amount of visceral adipose tissue, and the administration of dexamethasone was considered as a factor influencing inflammation. The Visual Analogue Scale (VAS) was used to determine postoperative pain. Patients were consecutively recruited between 1 September 2020 and 31 March 2022. Results: A total of 135 consecutive patients were included. The median waist-hip ratio was 0.55. The median duration of the pneumoperitoneum was 143 min. The median values of the average and maximum IAP values were 10 mmHg and 15 mmHg, respectively. The mean CRP of the first postoperative day was 6.2 mg/dL. The median VAS pain level decreased from 2 to 1 from the first to the third postoperative day. On the first postoperative day, 16 patients complained of shoulder pain. In addition, 134 patients were given some form of opioid pain treatment following surgery. Conclusion: We could not identify any relevant associations between the duration and IAP of the pneumoperitoneum and the indirect markers of inflammation or indicators of pain, or between the latter and the amount of visceral adipose tissue. In addition, we found no significant effect of the administration of dexamethasone on postoperative inflammation. The results point to a noninferior tolerability of moderate pressure during the procedure compared to the commonly utilised higher pressure, yet this must be confirmed in randomised controlled trials.

The Treatment of Diabetic Retinal Edema with Intravitreal Steroids: How and When.

Diabetic macular edema (DME) is a common complication of diabetes mellitus and a leading cause of visual impairment worldwide. It is defined as the diabetes-related accumulation of fluid, proteins, and lipids, with retinal thickening, within the macular area. DME affects a significant proportion of individuals with diabetes, with the prevalence increasing with disease duration and severity. It is estimated that approximately 25-30% of diabetic patients will develop DME during their lifetime. Poor glycemic control, hypertension, hyperlipidemia, diabetes duration, and genetic predisposition are recognized as risk factors for the development and progression of DME. Although the exact pathophysiology is still not completely understood, it has been demonstrated that chronic hyperglycemia triggers a cascade of biochemical processes, including increased oxidative stress, inflammation, activation of vascular endothelial growth factor (VEGF), cellular dysfunction, and apoptosis, with breakdown of the blood-retinal barriers and fluid accumulation within the macular area. Early diagnosis and appropriate management of DME are crucial for improving visual outcomes. Although the control of systemic risk factors still remains the most important strategy in DME treatment, intravitreal pharmacotherapy with anti-VEGF molecules or steroids is currently considered the first-line approach in DME patients, whereas macular laser photocoagulation and pars plana vitrectomy may be useful in selected cases. Available intravitreal steroids, including triamcinolone acetonide injections and dexamethasone and fluocinolone acetonide implants, exert their therapeutic effect by reducing inflammation, inhibiting VEGF expression, stabilizing the blood-retinal barrier and thus reducing vascular permeability. They have been demonstrated to be effective in reducing macular edema and improving visual outcomes in DME patients but are associated with a high risk of intraocular pressure elevation and cataract development, so their use requires an accurate patient selection. This manuscript aims to provide a comprehensive overview of the pathology, epidemiology, risk factors, physiopathology, clinical features, treatment mechanisms of actions, treatment options, prognosis, and ongoing clinical studies related to the treatment of DME, with particular consideration of intravitreal steroids therapy.

Effectiveness of Single Intravenous Dexamethasone in Prolongation of Spinal Anesthesia for Postoperative Analgesia in Elective Cesarean Section: A Systematic Review of Randomized Controlled Trials.

Background: The analgesic effectiveness of a single perioperative dose of dexamethasone is not clearly defined. The administration of systemic medication like dexamethasone, opioids, and non-steroidal anti-inflammatory drugs has a positive effect on the prolongation of postoperative analgesia after cesarean section under spinal anesthesia. A single-dose administration of dexamethasone with moderate to high dose reduces postoperative pain, reduces opioid consumption, and prolongs spinal anesthesia after cesarean delivery. Objective: The aim of this systematic review was to investigate the effectiveness of single intravenous dexamethasone in prolongation of spinal anesthesia for postoperative analgesia in elective cesarean section. Methods: We conducted a search on PubMed, Google Scholar, the Cochrane Library, Hinari, and review articles on the effectiveness of intravenous dexamethasone for extending spinal anesthesia during elective cesarean sections, until June 2023. The searches were conducted by using keyword (IV dexamethasone OR/AND analgesia OR postoperative pain AND cesarean section OR child birth AND prolongation of spinal anesthesia). The articles included describe the analgesic efficacy of dexamethasone for prolongation of spinal anesthesia during cesarean section. Results: A total of 25,384 papers were found using different searching methodologies from different electronic databases. The EndNote reference manager was used to remove duplicates, and 438 articles were selected for screening. Of those, 57 were included for critical evaluation, and 49 were removed with justification. The effectiveness of IV dexamethasone on the prolongation of spinal anesthesia and postoperative analgesia in women undergoing cesarean delivery is the subject of eight RCT studies on 628 parturients that are presented in the chosen journal articles from various countries. Conclusion: Intravenous dexamethasone administration immediately after clamping of the umbilical cord prolongs the duration of spinal block in patients undergoing cesarean sections and has a significant impact on reduction of postoperative pain severity, opioid consumption, and other pain requirements. When high-dose dexamethasone is administered intravenously, it can overcome complications that may arise after severe pain and increase patient satisfaction by extending the duration of postoperative analgesia and sensory block.

Comparing the efficacy of glucocorticoids and anti-VEGF in treating diabetic macular edema: systematic review and comprehensive analysis.

Introduction: The aim of this study was to better understand the efficacy of various drugs, such as glucocorticoids and anti-vascular endothelial growth factors (VEGF), in the treatment of diabetic macular edema (DME), and to evaluate various clinical treatment regimens consisting of different therapeutic measures. Methods: This study included randomized controlled trials up to February 2023 comparing the efficacy of corticosteroid-related therapy and anti-VEGF therapy. PubMed, the Cochrane Library, and Embase were searched, and the quality of the studies was carefully assessed. Finally, 39 studies were included. Results: Results at 3-month followup showed that intravitreal injection of bevacizumab (IVB) + triamcinolone acetonide (TA) was the most beneficial in improving best-corrected visual acuity and reducing the thickness of macular edema in the center of the retina in patients with DME. Results at 6-month follow-up showed that intravitreal dexamethasone (DEX) was the most effective in improving patients' bestcorrected visual acuity and reducing the thickness of central macular edema. Discussion: Overall, IVB+TA was beneficial in improving best-corrected visual acuity and reducing central macular edema thickness over a 3-month follow-up period, while DEX implants had a better therapeutic effect than anti-VEGF agents at 6 months, especially the patients with severe macular edema and visual acuity impaired. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=397100, identifier CRD42023397100.

Chronic hyperglycemia and intracranial meningiomas.

Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.