Who and how to screen for endogenous hypercortisolism in type 2 diabetes mellitus or obesity.

PURPOSE: The current review aims to summarize and discuss the prevalence of confirmed hypercortisolism in patients with diabetes mellitus or obesity, analysing the screening tests used and their accuracy, in order to better identify whether patients with diabetes mellitus and obesity should be screened for Cushing's syndrome (CS) and how. METHODS: A narrative review was performed including publications focusing on the current knowledge on prevalence of confirmed hypercortisolism in patients with type 2 diabetes mellitus (T2DM) or obesity and on screening tests used to detect CS. RESULTS: The studies reviewed suggest that the prevalence of CS in patients with T2DM is variable, ranging from 0.6 to 9.3%. The most used screening test is the overnight cortisol after 1 mg of dexamethasone suppression test (DST), with a false positive rate ranging from 3.7 to 21%. The prevalence of CS among obese patients is generally about 1%, except for two studies which reported higher prevalence. For obese patients, 1 mg DST and late-night salivary cortisol are the most accurate screening tests for CS. CONCLUSIONS: Clinical expertise remains the mainstay to identify which subjects should be screened for CS. The evaluation of the clinical stigmata of CS and the combination with clinical comorbidities typical of CS are the stronger predictors of CS. In addition, we could hypothesize that in patients with T2DM, overnight 1 mg DST is the more accurate screening test for CS. By contrast, in patients with obesity both LNSC and overnight 1 mg DST could be equally used for the screening of hypercortisolism.

A randomized phase III study evaluating dexamethasone-based mouthwash to prevent chemotherapy-induced stomatitis in patients with breast cancer.

Stomatitis, which is a common side effect of chemotherapy, currently lacks a standardized approach for its prevention. Therefore, this multicenter, randomized, open-label, controlled phase III trial aims to assess the efficacy and safety of a dexamethasone-based mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. We will randomly assign 230 patients with early breast cancer scheduled to receive chemotherapy in a 1:1 ratio to either the dexamethasone-based mouthwash group (10 ml, 0.1 mg/ml; swish for 2 min and spit 4 times daily for 8 weeks) or the mouthwash-with-tap-water group. The incidence of stomatitis, measured using electronic patient-reported outcomes, is the primary endpoint.

The effect of dexamethasone and bupivacaine on postoperative pain and nausea and vomiting by preperitoneal nerve blocking in laparoscopic cholecystectomy: a randomized clinical trial.

Background: This study aims to examine the effects of preperitoneal administration of dexamethasone and bupivacaine surrounding laparoscopic trocars on postoperative pain (POP) and nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy (LC). Method: In this randomized triple-blinded trial with a 1:1 randomization ratio, 104 patients with chronic cholecystitis were candidates for elective LC. A total of 40 mg (8 ml) of bupivacaine was mixed with 8 mg (2 ml) of dexamethasone or normal saline. The solution was injected preperitoneally via an 18G needle parallel and lateral to trocars until a bulge in the interior surface of the parietal peritoneum was observed by the camera. Primary outcomes were the severity of POP based on 0-10 Likert visual analog scale (VAS) and rates of PONV and secondary outcomes were rate of postoperative opioid usage and any side-effects. Result: The mean VAS score was significantly lower in the dexamethasone group (3.5 vs. 6.2, P<0.001). The dexamethasone group had 46.2% and 26.9% lower rates of nausea and vomiting after LC compared to the other group (P=0.001 and 0.015, respectively). Postoperative opioid use was lower in the dexamethasone group, but its difference was insignificant (P=0.3). Conclusions: Preperitoneal dexamethasone injection around laparoscopic trocars may lower the intensity of POP and PONV rates. Perioperative local corticosteroids can be used as an effective, available, and inexpensive analgesic and antiemetic prevention for laparoscopic procedures.

Topical Application of Dexamethasone-Loaded Core-Multishell Nanocarriers Against Oral Mucosal Inflammation.

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C0.08). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C0.08 loaded with dexamethasone (Dx-CMS-C0.08) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C0.08 over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

Comparison of aprepitant versus ondansetron for prevention of postoperative nausea and vomiting: A systematic review and meta-analysis with trial sequential analysis.

Background and Aims: Postoperative nausea and vomiting (PONV) is a common complication after surgery. Preventing PONV in high-risk patients often requires a multimodal approach combining antiemetic drugs with diverse mechanisms. While aprepitant, a neurokinin-1 receptor antagonist, is recognised as highly effective for PONV prevention, uncertainties remain regarding its effectiveness. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The analysis assessed the effectiveness of aprepitant (A), aprepitant plus ondansetron (AO) and aprepitant plus dexamethasone and ondansetron (ADO) in preventing PONV compared to ondansetron alone (O) or in combination with dexamethasone (DO). Results: In the analysis of 12 studies involving 2729 patients, aprepitant demonstrated significant efficacy in preventing PONV compared to ondansetron alone (A versus [vs.] O: PONV incidence 12.5% vs. 28.5%, relative risk [RR] = 0.45, P < 0.001; complete response rate 55.97% vs. 50.35%, RR = 1.13, P = 0.010). The combination of aprepitant with ondansetron (AO) also showed a significantly lower incidence of PONV compared to ondansetron alone (11.3% vs. 26.8%, RR = 0.43, P < 0.001) and a higher complete response rate (38.1% vs. 26.84%, RR = 1.41, P = 0.020). In addition, ADO significantly reduced PONV incidence compared to DO (ADO vs. DO: 13.63% vs. 35.38%, RR = 0.38, P = 0.006). Conclusion: Aprepitant, whether used alone or in combination with ondansetron or both ondansetron and dexamethasone, consistently outperforms ondansetron in achieving a complete response as it lowers vomiting rates and reduces the need for rescue therapy during the crucial 24-48-h postoperative period.

Hydrogel Matrix Containing Microcarriers for Dexamethasone Delivery to Protect Against Cisplatin-Induced Hearing Loss.

A functional hydrogel containing biopolymer microcarriers loaded with dexamethasone was developed to address the hearing loss that results from cisplatin ototoxicity. The drug delivery platform was tested both in vitro in the HEI-OC1 inner ear cell line and in vivo in a rat animal model. The newly described formula offered prolonged release of the contained dexamethasone for up to six days and transformed into a solid state at body temperature, thus counteracting its clearing through the Eustachian tube when injected into the middle ear. When tested in vitro, the inner ear cells exposed to cisplatin showed significantly higher viability at 48 hours when seeded on hydrogel containing dexamethasone-loaded microparticles than the cells treated with free dexamethasone. In the rat in vivo model, the ears of the rats treated with the hydrogel formulation presented better hearing thresholds after cisplatin administration than contralateral ears treated with free dexamethasone. The ears of the rats treated with microcarriers without inclusion in the functional hydrogel obtained better results than the dexamethasone treatment group but not as good as the hydrogel-containing microcarrier group. Histological assessment of the rats' inner ears showed better integrity of the structures and lower apoptosis in the microcarrier-treated groups than in the control group. Overall, the newly described microcarrier of dexamethasone offers better protection against cisplatin-induced hearing loss than free dexamethasone, especially when contained in a functional hydrogel formulation.

Effects of dexamethasone on the EC50 of remifentanil combined with dexmedetomidine achieving analgesia during pancreatic extracorporeal shockwave lithotripsy: a prospective, randomized and controlled study.

BACKGROUND: In addition to their classic genomic effects, glucocorticoids also manifest rapid non genomic effects. We speculate that dexamethasone has the potential prompt onset of analgesic effects. The objective of this study is to investigate the influence of a single preoperative dose of dexamethasone on the half maximal effective concentration (EC50) of remifentanil when combined with dexmedetomidine for pain relief during pancreatic extracorporeal shockwave lithotripsy (P-ESWL). METHODS: A total of 60 patients undergoing P-ESWL were enrolled and randomized at 1:1 ratio into the dexamethasone (DXM) group and the placebo group. Before anesthesia induction, patients in DXM group received an intravenous injection of 8 mg dexamethasone, while subjects in placebo group received an equal dose of physiological saline. Monitored anesthesia care (MAC) was performed based on remifentanil in combination with dexmedetomidine. Remifentanil was administered by TCI with an initial target concentration of 2.5 µg/mL for both groups. A positive response was defined as that VAS score > 3 by the patient at any time during the procedure. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.3 ng/mL intervals, based on the response of the previous patient. The EC50 of remifentanil for pain relief during P-ESWL treatment was calculated using Dixon's up-and-down method. Hemodynamic variables, oxygen saturation and adverse events were also recorded. RESULTS: Dixon up-and-down method revealed that the EC50 of remifentanil was significantly higher in placebo group (2.65 ± 0.28 ng/mL) than in DXM group (2.02 ± 0.23 ng/ml) (P < 0.001). Hemodynamic parameter exhibited a significant decrease in mean arterial pressure (MAP) and heart rate (HR) before and after induction in placebo group; however, data of the two groups were comparable (P>0.05). Less adverse events occurred in DXM group, including the incidence of postoperative nausea and vomiting (PONV) and analgesia requirement with in the first 24 h following the procedure at ward. CONCLUSION: Dexamethasone exerted analgesic effects with a rapid onset, and patients received dexamethasone 8 mg preoperative had a lower required EC50 of remifentanil during P-ESWL. It is also associated with reduced PONV in addition to reduced postoperative analgesic consumption in the first postoperative 24 h. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300078171) on 30/11/2023.

IS Intra-masseteric Dexamethasone Better than Intra-deltoid Injection in Reducing Post-operative Sequelae Following Impacted Third Molar Surgery?: A Randomized Clinical Study.

Aim: The post-operative sequelae of third molar surgical extractions need to be controlled in order to reduce patient morbidity. Dexamethasone is a well-researched drug which has established its merit as an anti-inflammatory agent. The aim of this randomized clinical study was to compare the patient-centric outcomes after pre-emptive intramuscular injection of dexamethasone into the masseter and deltoid, respectively. Materials and Methods: The outcomes measured were pain, facial swelling and mouth-opening postoperatively on Day 1, 3 and 7. The subjects were randomly divided into two groups. Group 1 received an intra-oral injection of 8 mg of dexamethasone into the masseter muscle and a placebo injection of distilled-water into the deltoid muscle 2 h before surgical removal of impacted mandibular third molar. Group 2 received an intra-oral placebo injection of distilled-water into masseter muscle and an 8 mg injection of dexamethasone into deltoid muscle. Results: On comparison, Group 1 patients experienced statistically significant less pain (VAS score on day 1, 3, and 7), facial swelling (day 1, 3), and restricted mouth-opening (day 1, 3). Conclusion: The study concluded that pre-emptive dexamethasone injection, at masseter or deltoid, is helpful in reducing post-operative sequelae of mandibular third molar extraction. However, the immediate post-operative outcomes were found to be better mitigated when the injection was administered locally into masseter muscle.

The impact of intravenous versus submucosal dexamethasone on short-term patient response: A randomized controlled trial.

BACKGROUND: The purpose of this randomized, cross-over trial was to determine if a preoperative dose of dexamethasone administered submucosally is as effective as intravenous (IV) dexamethasone in reducing pain, swelling, and analgesic consumption after periodontal flap surgery. METHODS: Thirty-nine patients planned for two similar flap surgeries under IV sedation were included. Before the first surgery, patients were randomized to receive 8 mg of IV or submucosal dexamethasone. Via the alternate route, 0.9% sodium chloride (placebo) was administered. Dexamethasone was administered via the opposite route during the second surgery. A standardized regimen of 600 mg ibuprofen and 325 mg acetaminophen was used to manage postoperative pain. Patients recorded pain and swelling levels on a 21-point numerical rating scale (NRS-21) and a four-point visual rating scale (VRS-4), as well as analgesic usage via a phone application at 12, 24, 48, 72, and 168 h postoperatively. RESULTS: While NRS-21 and VRS-4 data suggest a trend toward decreased pain and swelling with IV administration, there were no significant differences in analgesic usage or pain at any time and a significant difference in swelling only at 72 h in favor of IV administration (p = 0.047). CONCLUSIONS: There was no significant difference in pain or analgesic usage following periodontal flap surgery comparing IV and submucosal dexamethasone. A statistically significant difference in swelling between groups at 72 h is likely of limited clinical relevance. Submucosal dexamethasone is an effective way to mitigate pain following periodontal surgery, particularly when IV access for sedation is not required.

Intravitreal Dexamethasone Implants for Macular Edema Secondary to Acute Retinal Necrosis.

PURPOSE: To assess the effectiveness and risk of intravitreal injection of dexamethasone implants in treating macular edema (ME) secondary to acute retinal necrosis (ARN). METHODS: In this retrospective, noncomparative case series study, five patients who developed secondary ME after ARN and received an intravitreal dexamethasone implant injection were enrolled. The features of secondary ME on OCT and the outcomes of dexamethasone intravitreal implanting were presented. RESULTS: The mean age of the patients was 59 years (range, 51-61 years). All patients had unilateral involvement, and all 5 eyes showed mild to moderate anterior uveitis, retinal necrosis, and vasculitis. Herpes zoster virus was detected in all eyes using PCR, and timely antiviral and anti-inflammatory treatment was performed. Aqueous humor samples were negative for herpes zoster virus DNA, and resolution of viral retinitis was noted upon the occurrence of ME. Additionally, three eyes received pars plana vitrectomy with silicone oil prior to ME development. All eyes presented with intraretinal fluid, hyper-reflective foci, and impairments of the external limiting membrane/ellipsoid zone at varying degrees on OCT images. Epiretinal membrane was exhibited in 80% of eyes, but no vitreoretinal traction was detected. Subretinal fluid was visible in 60% of eyes. ME was relieved effectively in all eyes after intravitreal dexamethasone implanting. One of these patients experienced three episodes of ME. No recurrence of retinal necrosis or corticosteroid-associated ocular hypertension was observed during the follow-up period. CONCLUSION: Intravitreal injection of dexamethasone implants can effectively alleviate ME secondary to ARN and improve visual acuity with no adverse reactions.

Macular edema secondary to acute retinal necrosis was characterized by the presence of intraretinal fluid, hyper-reflective foci, and external limiting membrane/ellipsoid zone fracture. The intravitreal injection of dexamethasone implants effectively alleviated this type of edema with no adverse reactions.

Treatment Options in Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP): Case Presentation and Review of the Literature.

PURPOSE: To outline the therapeutic approach for a rare case of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) and examine the current management recommendations of this uncommon condition. METHODS-RESULTS: Literature review on the current treatment options in BDUMP cases. An 82-year-old woman was referred to our clinic due to bilateral visual loss. She was treated elsewhere with anti-vascular endothelial growth factors (anti-VEGF) in both eyes for presumed choroidal neovascularization (CNV) without improvement. Her past medical history (PMH) entailed colon cancer, treated with surgical resection and adjuvant chemotherapy 15 years ago. The patient presented with low visual acuity in both eyes, multiple oval orange patches in the fundus with striking hyperfluorescent pattern in fluorescein angiography (FA), giraffe pattern in fundus autofluorescence (FAF) and rapidly progressive cataracts. Intravitreal dexamethasone implants were administered with mild improvement and subretinal fluid absorption. CONCLUSIONS: The management strategy in BDUMP should focus on the systemic, often occult malignancy. There is no standard treatment protocol for BDUMP; however, plasmapheresis in combination with primary malignancy treatment seems to yield promising results in current literature reports. Anti-VEGF injections failed to control BDUMP sequelae, however intravitreal dexamethasone implants may offer temporary relief.

Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.

Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues. We achieved a conjugation efficiency exceeding 98 % using a cosolvent system, with subsequent ester bond cleavage releasing the active Dex, as verified by liquid chromatography. Biodistribution and cellular uptake studies indicated the potential of the HA conjugate for cluster of differentiation 44 (CD44)-mediated targeting and accumulation. In a lipopolysaccharide-induced ALI mouse model, intravenous (IV) HA-Dex administration showed superior anti-inflammatory effects compared to free Dex administration. Flow cytometry analysis suggested that the HA conjugate preferentially accumulated in lung macrophages, suggesting the possibility of reducing clinical Dex dosages through this targeted delivery approach.

Dexamethasone versus 5-HT3 receptor antagonists in preventing nausea during awake craniotomy: a propensity score matching study.

BACKGROUND: Nausea and vomiting during awake craniotomy (AC) can increase cerebral pressure and cause asphyxia and aspiration. 5-HT3 receptor antagonists, such as granisetron, are often administered before awakening to prevent nausea during AC. Recently, dexamethasone was reported to prevent nausea and vomiting during AC; however, the efficacy of both drugs in preventing nausea has not yet been investigated. METHODS: We examined the frequency of nausea and vomiting in AC patients (n = 170) treated at our hospital until the end of September 2019. We divided patients as those who received dexamethasone (n = 71) and or granisetron (n = 99) before awakening and examined the frequency of nausea and vomiting after propensity score (PS) matching. RESULT: Eighty-two patients were selected after PS matching. The incidence of nausea was significantly lower in the dexamethasone group than in the granisetron group (9.8% vs 41.5%, p = 0.002). In the logistic regression analysis after matching, the incidence of nausea significantly reduced with dexamethasone treatment (odds ratio: 0.12, 95% confidence interval: 0.029-0.499, p = 0.03). CONCLUSION: In conclusion, dexamethasone was more effective than granisetron in preventing nausea during AC.

Suppressive Effects of Arriheuk Wheat Sprout Extract on Muscle Atrophy in Dexamethasone-Induced C2C12 Myotubes and a Mouse Model.

Skeletal muscle atrophy refers to the loss of muscle strength and mass due to decreased protein synthesis or increased protein degradation. Various conditions can cause muscle atrophy, including aging, heart disease, chronic illness, obstructive pulmonary disease, kidney failure, diabetes, AIDS, cancer, sepsis, and steroid use. Various natural materials have been studied for the prevention of muscle atrophy. In this study, we found that extracts from the sprouts of purple wheat, Arriheuk, prevented muscle atrophy in vitro and in vivo. Arriheuk wheat sprouts extract inhibited the expression of muscle protein breakdown factors, which were increased by dexamethasone, and improved muscle strength. In C2C12 myotubes, Arriheuk wheat sprout extract (ARE) protected against dexamethasone-induced muscle atrophy by potentiating Akt/mammalian target of rapamycin and AMP-activated protein kinase (AMPK)/forkhead box O3 (AMPK/Foxo3) signaling and inhibiting the expression of Atrogin-1, muscle RING-finger protein-1 (MuRF1), and Myostatin. In addition, the administration of ARE in an animal model of muscle atrophy induced by dexamethasone prevented myocardial and muscle strength loss by regulating the expression of muscle atrophy-related factors by affecting AMPK/Foxo3 signaling. Taken together, these results suggest that Arriheuk wheat sprouts extract effectively alleviates muscle atrophy by regulating the synthesis and breakdown of muscle proteins.

A Comparative Study of Post Operative Pain Following Tonsillectomy with Local Infilteration of Dexamethasone vs Triamcinolone.

Tonsillectomy till date continues to be the most frequently performed surgery by ENT surgeons, and with that comes the most challenging complication of post-tonsillectomy pain and its management that affects the patient morbidity and alters the hospital course. Various methods and techniques have been implicated in the post-operative pain management in patients undergoing tonsillectomy. To compare the post operative pain following local infiltration of Dexamethasone and Triamcinolone in patients undergoing Tonsillectomy. Total of 50 patients were selected and randomized into two groups- Group 1 and Group 2, who underwent local infiltration of Dexamethasone and Triamcinolone respectively to maintain uniformity. Baseline scoring (0 h post operatively) and follow up scoring after 6 h and 24 h was done using the Visual Analogue Scale and were evaluated and documented as per their response to treatment. A significant reduction was observed in the severity of pain in both groups with an average reduction of mean score from 9.50 to 5.92 in Group 1 and from 9.04 to 3.90 in Group 2 at the end of 24 h post-operatively. The mean score of Group 2 was greater and showed better improvements in VAS pain score and was statistically significant (p < 0.001). Usage of steroidal preparations locally during tonsillectomy helps combat the post-operative pain. Usage of Triamcinolone locally has proved beneficial in reducing the post-operative tonsillectomy pain.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. AIM: To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. METHODS: Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. RESULTS: From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). CONCLUSION: Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

The efficacy of tobramycin dexamethasone combined with pranoprofen in middle-aged and elderly post-cataract patients and the value of improving inflammatory factor levels.

OBJECTIVE: To analyze the effect of tobramycin dexamethasone combined with pranoprofen on middle-aged and elderly patients after cataract surgery. METHODS: In this retrospective study, the clinical data from 108 middle-aged and elderly patients who had cataract surgery in the Second Hospital of Longyan between January 2021 and December 2023 were collected. The patients were divided into two groups based on treatment methods, a control group (n=54) that received tobramycin dexamethasone treatment, and an observation group (n=54) that treated with additional pranoprofen. The treatment effects in the two groups were compared. RESULTS: Significant differences were observed between the groups at 1 day, 1 week, 3 weeks, and 5 weeks post-treatment in terms of ocular symptom scores, signs scores, and intraocular pressure levels (all P < 0.05). The observation group demonstrated lower levels of inflammatory markers post-treatment (P < 0.05). Additionally, at 1 week, 3 weeks and 5 weeks after treatment, significant differences were noted in anterior chamber flare value, best-corrected visual acuity (BCVA), macular center thickness, degree of corneal edema, and posterior lens capsular opacity grading scores (all P < 0.05). The incidence of increased intraocular pressure and conjunctival congestion was 3.7% in the observation group, slightly lower than 7.41% in the control group (P > 0.05). CONCLUSION: The combination of pranoprofen and tobramycin dexamethasone can improve the inflammatory reaction, ocular symptoms, anterior chamber flare value, macular center thickness, corneal oedema, and clarity of the posterior lens capsule in middle-aged and elderly cataract patients. This regimen also helps restore intraocular pressure and visual acuity of the patients, with relatively low adverse reactions, indicating an ideal clinical outcome.

Electrical stimulation of biofidelic engineered muscle enhances myotube size, force, fatigue resistance, and induces a fast-to-slow-phenotype shift.

Therapeutic development for skeletal muscle diseases is challenged by a lack of ex vivo models that recapitulate human muscle physiology. Here, we engineered 3D human skeletal muscle tissue in the Biowire II platform that could be maintained and electrically stimulated long-term. Increasing differentiation time enhanced myotube formation, modulated myogenic gene expression, and increased twitch and tetanic forces. When we mimicked exercise training by applying chronic electrical stimulation, the "exercised" skeletal muscle tissues showed increased myotube size and a contractility profile, fatigue resistance, and gene expression changes comparable to in vivo models of exercise training. Additionally, tissues also responded with expected physiological changes to known pharmacological treatment. To our knowledge, this is the first evidence of a human engineered 3D skeletal muscle tissue that recapitulates in vivo models of exercise. By recapitulating key features of human skeletal muscle, we demonstrated that the Biowire II platform may be used by the pharmaceutical industry as a model for identifying and optimizing therapeutic drug candidates that modulate skeletal muscle function.

Neutrophil Hitchhiking Enhances Liposomal Dexamethasone Therapy of Sepsis.

Sepsis is characterized by a dysregulated immune response and is very difficult to treat. In the cecal ligation and puncture (CLP) mouse model, we show that nanomedicines can effectively alleviate systemic and local septic events by targeting neutrophils. Specifically, by decorating the surface of clinical-stage dexamethasone liposomes with cyclic arginine-glycine-aspartic acid (cRGD) peptides, we promote their engagement with neutrophils in the systemic circulation, leading to their prominent accumulation at primary and secondary sepsis sites. cRGD-targeted dexamethasone liposomes potently reduce immature circulating neutrophils and neutrophil extracellular traps in intestinal sepsis induction sites and the liver. Additionally, they mitigate inflammatory cytokines systemically and locally while preserving systemic IL-10 levels, contributing to lower IFN-γ/IL-10 ratios as compared to control liposomes and free dexamethasone. Our strategy addresses sepsis at the cellular level, illustrating the use of neutrophils both as a therapeutic target and as a chariot for drug delivery.

Prenatal and Pregnancy Management of Congenital Adrenal Hyperplasia.

Management of patients with congenital adrenal hyperplasia (CAH) poses challenges during pregnancy and prenatal stages, impacting fertility differently in men and women. Women with CAH experience menstrual irregularities due to androgen and glucocorticoid precursor interference with endometrial development and ovulation. Genital surgeries for virilization and urogenital anomalies further impact fertility and sexual function, leading to reduced heterosexual relationships among affected women. Fertility rates vary, with a lower prevalence of motherhood, primarily among those with classic CAH, necessitating optimized hormonal therapy for conception. Monitoring optimal disease control during pregnancy poses challenges due to hormonal fluctuations. Men with CAH often experience hypogonadotrophic hypogonadism and complications like testicular adrenal rest tissue, impacting fertility. Regular monitoring and intensified glucocorticoid therapy may restore spermatogenesis. Genetic counselling is vital to comprehend transmission risks and prenatal implications. Prenatal dexamethasone treatment in affected female fetuses prevents virilization but raises ethical and safety concerns, necessitating careful consideration and further research. The international "PREDICT" study aims to establish safer and more effective prenatal therapy in CAH, evaluating dosage, safety, and long-term effects.