Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial.

BACKGROUND: Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids. METHODS AND FINDINGS: We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments. CONCLUSIONS: There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.

Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

Background: Local infiltration analgesia (LIA) provides postoperative analgesia for total knee arthroplasty (TKA). The purpose of this study was to evaluate the analgesic effect of a cocktail of ropivacaine, morphine, and Diprospan for TKA. Methods: A total of 100 patients from September 2018 to February 2019 were randomized into 2 groups. Group A (control group, 50 patients) received LIA of ropivacaine alone (80 ml, 0.25% ropivacaine). Group B (LIA group, 50 patients) received an LIA cocktail of ropivacaine, morphine, and Diprospan (80 ml, 0.25% ropivacaine, 0.125 mg/ml morphine, and 62.5 µg/ml compound betamethasone). The primary outcomes were the levels of inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), pain visual analog scale (VAS) scores, opioid consumption, range of motion (ROM), functional tests, and sleeping quality. The secondary outcomes were adverse events, satisfaction rates, HSS scores, and SF-12 scores. The longest follow-up was 2 years. Results: The two groups showed no differences in terms of characteristics (P > 0.05). Group B had lower resting VAS pain scores (1.54 ± 0.60, 95% CI = 1.37 to 1.70 vs. 2.00 ± 0.63, 95% CI = 2.05 to 2.34) and active VAS pain scores (2.64 ± 0.62, 95% CI = 2.46 to 2.81 vs. 3.16 ± 0.75, 95% CI = 2.95 to 3.36) within 48 h postoperatively than Group A (P < 0.001), while none of the pain differences exceeded the minimal clinically important difference (MCID). Group B had significantly lower CRP levels (59.49 ± 13.01, 95% CI = 55.88 to 63.09 vs. 65.95 ± 14.41, 95% CI = 61.95 to 69.94) and IL-6 levels (44.11 ± 13.67, 95% CI = 40.32 to 47.89 vs. 60.72 ± 15.49, 95% CI = 56.42 to 65.01), lower opioid consumption (7.60 ± 11.10, 95% CI = 4.52 to 10.67 vs. 13.80 ± 14.68, 95% CI = 9.73 to 17.86), better ROM (110.20 ± 10.46, 95% CI = 107.30 to 113.09 vs. 105.30 ± 10.02, 95% CI = 102.52 to 108.07), better sleep quality (3.40 ± 1.03, 95% CI = 3.11 to 3.68 vs. 4.20 ± 1.06, 95% CI = 3.90 to 4.49), and higher satisfaction rates than Group A within 48 h postoperatively (P < 0.05). Adverse events, HSS scores, and SF-12 scores were not significantly different within 2 years postoperatively. Conclusions: A cocktail of ropivacaine, morphine, and Diprospan prolongs the analgesic effect up to 48 h postoperatively. Although the small statistical benefit may not result in MCID, the LIA cocktail still reduces opioid consumption, results in better sleeping quality and faster rehabilitation, and does not increase adverse events. Therefore, cocktails of ropivacaine, morphine, and Diprospan have good application value for pain control in TKA. This trial is registered with ChiCTR1800018372.

Development of double-layer poly (amino acid) modified electrochemical sensor for sensitive and direct detection of betamethasone in cosmetics.

Screening for illegal use of glucocorticoids (GCs) in cosmetics by electrochemical methods is extremely challenging due to the poor electrochemical activity of GCs. In this study, poly-L-Serine/poly-Taurine modified electrode (P(Tau)/P(L-Ser)/GCE) was prepared for sensitive and direct determination of betamethasone in cosmetics by a simple two-step in situ electropolymerization reaction. The relevant parameters of preparation and electroanalytical conditions were respectively studied, including the concentration of polymerization solution, the number of scanning circles and the scanning rate. The SEM and EDS mapping demonstrated successful preparation of P(Tau)/P(L-Ser)/GCE. The electro-catalytic properties of the obtained electrodes were investigated using cyclic voltammetry and differential pulse voltammetry methods, showing a remarkable improvement of sensitivity for the detection of betamethasone due to the synergic effect of both P(L-Ser) and P(Tau). In addition, we investigated the electrochemical reduction of betamethasone on the surface of modified electrode. It was found that the process was controlled by diffusion effect and involved the transfer of two electrons and two protons. Then the electrochemical sensor method based on P(Tau)/P(L-Ser)/GCE was established and delivered a linear response to betamethasone concentration from 0.5 to 20 µg mL-1 with a limit of detection of 32.2 ng mL-1, with excellent recoveries (98.1%-106.8%) and relative standard deviations (＜4.8%). Furthermore, the established electrochemical sensor method was compared with conventional HPLC method. The results showed that both of them were comparable. Moreover, the established electrochemical sensor method was with the merits of short analysis time, environmentally friendly, low cost and easy to achieve in-site detection.

Late-Preterm Antenatal Steroids for Reduction of Neonatal Respiratory Complications: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of antenatal corticosteroids in reducing neonatal respiratory complications when administered to those at risk of preterm delivery between 34 and 36 6/7 weeks of gestation. METHODS: This was a single-center, triple-blind, randomized, placebo-controlled trial in southern India enrolling pregnant participants at risk of preterm delivery between 34 and 36 6/7 weeks of gestation. Computer-generated block randomization was used with participants randomized to either one course of intramuscular betamethasone or placebo. The primary outcome was a composite of treatment for respiratory distress in the neonate, defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life. Neonatal secondary outcomes were transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, hypoglycemia, stillbirth, and early neonatal death; maternal secondary outcomes were chorioamnionitis, postpartum hemorrhage, puerperal fever, and length of hospitalization. All analyses were based on intention to treat. A sample size of 1,200 was planned with 80% power to detect a 30% reduction in rates of respiratory distress. After a planned interim analysis, enrollment was stopped for futility. RESULTS: From March 2020 to August 2022, 847 participants were recruited, with 423 participants randomized to betamethasone and 424 participants randomized to placebo. There were 22 individuals lost to follow-up. There was no statistically significant difference in the primary outcome (betamethasone 4.9% vs placebo 4.8%, relative risk 1.03, 95% CI, 0.57-1.84, number needed to treat 786). There were no statistically significant differences in secondary neonatal or maternal outcomes. CONCLUSION: Betamethasone administered in the late-preterm period to those at risk for preterm delivery did not reduce the need for treatment of neonatal respiratory distress. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India, CTRI/2019/09/021321.

Scleritis following intravitreal brolucizumab injection: a case series.

BACKGROUND: This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. CASE PRESENTATION: Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon's capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. CASE 2: An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn't due to progression of nAMD. CONCLUSIONS: Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis.

PURPOSE: Interstitial lung diseases (ILDs) are caused by inflammation and/or fibrosis of alveolar walls resulting in impaired gas exchange. Hypersensitivity pneumonitis (HP) is the third most common type of ILDs. Corticosteroids are the mainstay treatment for HP. The use of intramuscular (IM) betamethasone or intravenous (IV) dexamethasone as weekly pulse doses has shown higher benefit than daily oral prednisolone for HP patients. The aim of this study is to directly compare different corticosteroids in terms of effectiveness and in monetary values and perform an economic evaluation. METHODS: One hundred and seven patients were tested for pulmonary function tests (PFTs) and inflammatory markers to assess the treatment effectiveness. A cost-effectiveness analysis (CEA) was performed. ICERs between 3 treatment groups were calculated. RESULTS: Post treatment, Krebs von den Lungen-6 (KL-6) levels significantly improved in betamethasone group from 723.22 ± 218.18 U/ml to 554.48 ± 129.69 U/ml (p = 0.001). A significant improvement in erythrocyte sedimentation rate (ESR) occurred in the dexamethasone group from 56.12 ± 27.97 mm to 30.06 ± 16.04 mm (p = 0.048). A significant improvement in forced expiratory volume (FEV1), forced vital capacity (FVC) and six-minute walk distance (6MWD) was observed within the three treatment groups. A significant improvement in oxygen desaturation percentage (SpO2) occurred within dexamethasone and betamethasone groups. Betamethasone and dexamethasone were found more cost-effective than prednisolone as their ICERs fell in quadrant C. Furthermore, ICER between betamethasone and dexamethasone was performed; a small difference in cost was found compared to the higher benefit of betamethasone. CONCLUSION: Betamethasone and dexamethasone were found to be more effective than prednisolone in improving the inflammatory reaction and the clinical features of HP patients. Betamethasone was found to be the best intervention in terms of cost against the effect.

A Randomized Controlled Trial of Betamethasone on Fatigue in Patients With Advanced Cancer.

CONTEXT: Fatigue is one of the most uncomfortable physical symptoms seen in patients with advanced cancer. Previous studies have reported on the efficacy of corticosteroids from Western countries. OBJECTIVES: To assess the effectiveness of 4mg betamethasone improving fatigue among Japanese patients with advanced cancer. METHODS: A randomized, double-blind, placebo-controlled trial enrolled eligible patients with advanced cancer expected to survive 1-2 months, with an Eastern Cooperative Oncology Group Performance Status of 2-3, and experiencing fatigue according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15-palliative criteria. Participants received twice-daily oral administration of 2 mg betamethasone (4 mg/d) or placebo for seven days, with fatigue assessed using EORTC QLQ-C15-PAL subscale and numerical rating scale (NRS) score (at baseline and day seven). The trial was registered under the University Hospital Medical Information Network (UMIN)000011913. RESULTS: Among the 267 screened patients, 81 were eligible, of which 70 were evaluable (betamethasone, 33; placebo, 37). The mean difference in the EORTC-QLQ-C15-PAL fatigue subscale was -8.2 (95% CIs: -22.3, 0.0; P = 0.178) and in a NRS for fatigue was -1.2 (95% CIs: -2.5, -0.01; P = 0.048), respectively. Emotional function, appetite loss, and global-health were slightly better in the betamethasone group than in the placebo group. CONCLUSION: The impact of betamethasone 4 mg/d on alleviating fatigue in patients with advanced cancer in the last weeks of life did not reach statistical significance in the EORTC-QLQ-C15-PAL as the primary endpoint, however, it was significant in the NRS, the secondary endpoint.

Effect of Perineural or Intravenous Betamethasone on Femoral Nerve Block Outcomes in Knee Arthroplasty: A Randomized, Controlled Study.

OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.

Bladder neck contracture following transurethral surgery of prostate: a retrospective single-center study.

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.

Physicochemical Stability and Compatibility of Mixtures of Ropivacaine with Dexamethasone or Betamethasone for Epidural Steroid Injections: An In Vitro Study.

BACKGROUND: Epidural steroid injections are widely used to treat spinal and radiating pain. However, crystal formation has recently been reported in mixtures of ropivacaine and nonparticulate steroids, commonly used in epidural steroid injections. OBJECTIVES: Our study assessed the physicochemical stability of mixtures of different nonparticulate steroids and ropivacaine and aimed to propose a safe regimen for epidural steroid injections. STUDY DESIGN: An in vitro protocol was used to examine the physicochemical stability of epidural steroid injection mixtures most commonly used at our institution. SETTING: In vitro laboratory study. METHODS: Twelve solutions were prepared by mixing 0.75% or 0.2% ropivacaine with dexamethasone or betamethasone at volume ratios of 1:1, 2:1, and 3:1 in propylene syringes at 24°C. The physical properties of the mixtures were observed with the naked eye and under a microscope, and their pH was measured. The concentration of each drug in the mixture was evaluated using high-performance liquid chromatography. RESULTS: None of the ropivacaine and dexamethasone mixtures showed macroscopic or microscopic crystal formation after 2 hours, and there were no significant changes in pH. The concentrations of the 2 drugs remained stable for up to 2 hours. In contrast, at least 10 mu-m crystals were observed microscopically and macroscopically in all mixtures of ropivacaine and betamethasone; the ropivacaine concentration was reduced by > 10% after one hour. LIMITATIONS: Confirming the stability of drugs in vitro does not ensure that their pharmacokinetics and pharmacodynamics remain unaltered in vivo. CONCLUSION: The combination of ropivacaine and betamethasone should be avoided because of their physicochemical instability. Combinations of ropivacaine and dexamethasone should be administered cautiously because they are more physicochemically stable than combinations of ropivacaine and betamethasone.

Biphasic release of betamethasone from an injectable HA hydrogel implant for alleviating lumbar disc herniation induced sciatica.

Epidural steroid injection (ESI) is a common therapeutic approach for managing sciatica caused by lumbar disc herniation (LDH). However, the short duration of therapeutic efficacy and the need for repeated injections pose challenges in LDH treatment. The development of a controlled delivery system capable of prolonging the effectiveness of ESI and reducing the frequency of injections, is highly significant in LDH clinical practice. In this study, we utilized a thiol-ene click chemistry to create a series of injectable hyaluronic acid (HA) based release systems loaded with diphasic betamethasone, including betamethasone dipropionate (BD) and betamethasone 21-phosphate disodium (BP) (BD/BP@HA). BD/BP@HA hydrogel implants demonstrated biocompatibility and biodegradability to matched neuronal tissues, avoiding artificial compression following injection. The sustained release of betamethasone from BD/BP@HA hydrogels effectively inhibited both acute and chronic neuroinflammation by suppressing the nuclear factor kappa-B (NF-κB) pathway. In a mouse model of LDH, the epidural administration of BD/BP@HA efficiently alleviated LDH-induced sciatica for at least 10 days by inhibiting the activation of macrophages and microglia in dorsal root ganglion and spinal dorsal horn, respectively. The newly developed HA hydrogels represent a valuable platform for achieving sustained drug release. Additionally, we provide a simple paradigm for fabricating BD/BP@HA for epidural injection, demonstrating greater and sustained efficiency in alleviating LDH-induced sciatica compared to traditional ESI and displaying potentials for clinical translation. This system has the potential to revolutionize drug delivery for co-delivery of both soluble and insoluble drugs, thereby making a significant impact in the pharmaceutical industry. STATEMENT OF SIGNIFICANCE: Lumbar disc herniation (LDH) is a common degenerative disorder leading to sciatica and spine surgery. Although epidural steroid injection (ESI) is routinely used to alleviate sciatica, the efficacy is short and repeated injections are required. There remains challenging to prolong the efficacy of ESI. Herein, an injectable hyaluronic acid (HA) hydrogel implant by crosslinking acrylated-modified HA (HA-A) with thiol-modified HA (HA-SH) was designed to achieve a biphasic release of betamethasone. The hydrogel showed biocompatibility and biodegradability to match neuronal tissues. Notably, compared to traditional ESI, the hydrogel better alleviated sciatica in vivo by synergistically inhibiting the neuroinflammation in central and peripheral nervous systems. We anticipate the injectable HA hydrogel implant has the potential for clinical translation in treating LDH-induced sciatica.

Pre-emptive infiltration with betamethasone and ropivacaine for postoperative pain in laminoplasty and laminectomy (PRE-EASE): a prospective randomized controlled trial.

BACKGROUND: Postoperative pain after laminoplasty and laminectomy occurs partially from local trauma of the paraspinal tissue. Finding a multimodal analgesic cocktail to enhance the duration and effect of local infiltration analgesia is crucial. Because of the rapid onset and long duration of action of betamethasone, the authors hypothesized that, a pre-emptive multimodal infiltration regimen of betamethasone and ropivacaine reduces pain scores and opioid demand, and improves patient satisfaction following laminoplasty and laminectomy. MATERIALS AND METHODS: This prospective, randomized, open-label, blinded endpoint study was conducted between 1 September 2021 and 3 June 2022, and included patients between the ages of 18 and 64 scheduled for elective laminoplasty or laminectomy under general anesthesia, with American Society of Anesthesiologists classification I/II. One hundred sixteen patients were randomly assigned to either the BR (Betamethasone-Ropivacaine) group or the R (Ropivacaine) group in a 1:1 ratio. Each group received pre-emptive infiltration of a total of 10 ml study solution into each level. Every 30 ml of study solution composed of 0.5 ml of betamethasone plus 14.5 ml of saline and 15 ml of 1% ropivacaine for the BR group, and 15 ml of 1% ropivacaine added to 15 ml of saline for the R group. Infiltration of epidural space and intrathecal space were avoided and the spinous process, transverse process, facet joints, and lamina were injected, along with paravertebral muscles and subcutaneous tissue. Cumulative 48 h postoperative butorphanol consumption via PCA (Patient-controlled analgesia) was the primary outcome. Intention-to-treat (ITT) principle was used for primary analysis. RESULTS: Baseline characteristics were identical in both groups ( P >0.05). The cumulative 48 h postoperative butorphanol consumption via PCA was 3.0±1.4 mg in the BR group ( n =58), and 7.1±1.2 mg in the R group ( n =58) ( P <0.001). Overall cumulative opioid demand was lower at different time intervals in the BR group ( P <0.001), along with the estimated median time of first analgesia demand via PCA (3.3 h in the BR group and 1.6 h in the R group). The visual analog scale (VAS) score at movement and rest were also significantly lower until 3 months and 6 weeks, respectively. No side effects or adverse events associated with the intervention were observed in this study. CONCLUSIONS: Pre-emptive analgesia with betamethasone and ropivacaine provides better postoperative pain management following laminoplasty and laminectomy, compared to ropivacaine alone. This is an effective technique worthy of further evaluation.

Neurodevelopment at 24 months corrected age in extremely preterm infants treated with dexamethasone alternatives during the late postnatal period: a cohort study.

The administration of dexamethasone has been associated with suboptimal neurodevelopment. We aimed to compare the development of extremely premature infants treated or not with alternatives to dexamethasone: betamethasone, hydrocortisone hemisuccinate. This retrospective cohort study included infants born before 29 weeks of gestational age, treated or not with late (day ≥ 7) postnatal steroids (betamethasone, hydrocortisone hemisuccinate). The neurodevelopment outcome was evaluated at 24 months corrected age, after adjustment on comorbidities of extreme prematurity. In order to analyse their overall development, data about growth and respiratory outcomes were collected. Among the 192 infants included, 59 (30.7%) received postnatal steroids. Suboptimal neurodevelopment concerned 37/59 (62.7%) postnatal steroid-treated and 43/133 (38.1%; p = 0.002) untreated infants. However, in multivariable analysis, only severe neonatal morbidity (p = 0.007) and male gender (p = 0.027) were associated with suboptimal neurodevelopment outcome at 24 months.  Conclusions: Betamethasone or hydrocortisone hemisuccinate treatment was not an independent risk for suboptimal neurological development, growth and respiratory outcomes assessed at 24 months corrected age in extremely premature infants.  Registration number: The study was registered on the ClinicalTrials.gov register: NCT05055193. What is Known: • Late postnatal steroids are used to treat bronchopulmonary dysplasia • Meta-analyses warned against the neurological risk of dexamethasone use during neonatal period. Early or late hydrocortisone hemisuccinate has been evaluated in multiple studies, none of which have reported an adverse effect on neurodevelopment at least to 2 years. Data about the use of betamethasone are scarce. What is New: • The risk of suboptimal neurodevelopment was higher among extremely premature infants who received postnatal steroids when compared to those who did not. • Betamethasone and hydrocortisone hemisuccinate treatment was not an independent risk factor for suboptimal neurodevelopment at 24 months corrected age.

Divergent Chemo- and Biocatalytic Route to 16ß-Methylcorticoids: Asymmetric Synthesis of Betamethasone Dipropionate, Clobetasol Propionate, and Beclomethasone Dipropionate.

16ß-Methylcorticoids are among the most important glucocorticoid steroids for the treatment of various dermatological disorders, respiratory infections, and other allergic reactions elicited during inflammatory responses of the human body. Betamethasone dipropionate, clobetasol propionate, and beclomethasone dipropionate are particularly noteworthy for their synthetic intractability. Despite five decades of research, these 16ß-methylcorticoids have remained challenging synthetic targets owing to insurmountable issues of reactivity, selectivity, and cost efficiency associated with all previously explored strategies. We herein report our practicability-oriented strategy toward the unified stereoselective synthesis of 16ß-methylcorticoids in 12.6-14.0 % overall yield from commercially available 9α-hydroxyandrost-4-ene-3,17-dione (9α-OH-AD). In this approach, the chiral C16ß-Me and C17α-OH groups of the corticosteroid D ring were installed via a substrate-controlled diastereo- and enantioselective Mn-catalyzed oxidation-reduction hydration of Δ4,9(11),16 -triene-3,20-dione. The C1-C2 double bond of the corticosteroid A ring was constructed using an unprecedented engineered 3-ketosteroid-Δ1 -dehydrogenase (MK4-KstD)-catalyzed regioselective Δ1 -dehydrogenation of Δ4,9(11) -diene-3,21-dione. This strategy provides a general method and a key precursor for the divergent synthesis of a variety of glucocorticoids and related steroidal drugs.

Factors associated with maternal hyperglycaemia and neonatal hypoglycaemia after antenatal betamethasone administration in women with diabetes in pregnancy.

AIMS: Bespoke glycaemic control strategies following antenatal corticosteroids for women with diabetes in pregnancy (DIP) may mitigate hyperglycaemia. This study aims to identify predictive factors for the glycaemic response to betamethasone in a large cohort of women with DIP. METHODS: Evaluation of a prospective cohort study of 347 consecutive DIP pregnancies receiving two doses of 11.4 mg betamethasone 24 h apart between 2017 and 2021 and treated with the Pregnancy-IVI intravenous insulin protocol. Regression modelling identified factors associated with maternal glycaemic time-in-range (TIR) and maternal insulin requirements following betamethasone. Factors associated with neonatal hypoglycaemia (glucose <2.6 mmol/L) in infants born within 48 h of betamethasone administration (n = 144) were investigated. RESULTS: The mean maternal age was 31.9 ± 5.8 years, with gestational age at betamethasone of 33.5 ± 3.4 weeks. Gestational diabetes was present in 81% (12% type 1; 7% type 2). Pre-admission subcutaneous insulin was prescribed for 63%. On-infusion maternal glucose TIR (4.0-7.8 mmol/L) was 83% [IQR 77%-90%] and mean on-IVI glucose was 6.6 ± 0.5 mmol/L. Maternal hypoglycaemia (<3.8 mmol/L) was uncommon (0.47 h/100 on-IVI woman hours). Maternal glucose TIR was negatively associated with indicators of insulin resistance (type 2 diabetes, polycystic ovary syndrome), late-pregnancy complications (pre-eclampsia, chorioamnionitis) and the 1-h OGTT result. Intravenous insulin requirements were associated with type of diabetes, pre-eclampsia and intrauterine infection, the 1-h OGTT result and the timing of betamethasone administration. Neonatal hypoglycaemia was associated with pre-existing diabetes but not with measures of glycaemic control. CONCLUSION: An intravenous infusion protocol effectively controls maternal glucose after betamethasone. A risk-factor-based approach may allow individualisation of therapy.

New Findings in the Multidisciplinary Management of a Fetal Intrapericardial Teratoma: A Case Report.

INTRODUCTION: Fetal intrapericardial teratoma is a rare tumor that can be diagnosed by antenatal ultrasonography early in pregnancy. CASE PRESENTATION: A fetal intrapericardial teratoma was detected on routine ultrasonography in the second trimester of pregnancy. At 31 weeks gestation, a marked increase in tumor size, fetal ascites, and pericardial effusion were observed, indicating that preterm delivery would be inevitable. Corticosteroid prophylaxis (24 mg of betamethasone in two doses of 12 mg 24 h apart) initiated for prophylaxis of respiratory distress syndrome led to a reduction in fetal ascites and pericardial effusion. Betamethasone therapy (4 mg/per day) was continued with the aim to postpone the expected date of delivery. Gestation was extended for more than 2 weeks. At 33 weeks and 5 days gestation, the neonate was delivered by elective cesarean section with ex utero intrapartum treatment and immediately submitted to fetal cardiac surgery. The infant was discharged from the hospital in good health about 4 months later. CONCLUSION: The present report draws attention to improvement in fetal status and extension of gestation achieved with maternal low-dose corticosteroid therapy on antenatal ultrasound finding of fetal ascites and pericardial effusion due to intrapericardial teratoma.

The efficacy of a transdermal hydrogel patch containing betamethasone dipropionate for treatment of chronic hand eczema: A single-blind, randomized and controlled trial.

BACKGROUND: Topical corticosteroids under occlusion have been used to enhance the treatment of eczema. However, no study has investigated the efficacy of a steroid-containing transdermal patch for the treatment of chronic hand eczema. METHODS: We conducted a randomized, controlled, assessor-blinded trial to determine the efficacy of a transdermal patch containing betamethasone dipropionate compared to topical betamethasone dipropionate ointment in the treatment of mild to moderate chronic hand eczema. The patients were included and assigned to receive either the transdermal patch once daily at night or the ointment twice daily for a period of 8 weeks. The outcomes were assessed using the Hand Eczema Severity Index (HECSI), Physical Global Assessment (PGA) score, self-reported compliance, level of patient satisfaction, quality of life, and side effects. RESULTS: Fifty-six patients completed this study. At 8 weeks, there was a significant reduction in the HECSI scores in both the transdermal patch and topical ointment groups compared to those measured at baseline (14.61 to 1.86, p < 0.001; 18.46 to 3.43, p < 0.001, respectively) without a statistically significant difference between the two groups. Similarly, the two groups did not show any significant difference in the PGA scores, quality of life and side effects. However, the transdermal patch group reported better compliance and a higher level of patient satisfaction than the topical ointment group. CONCLUSION: The transdermal corticosteroid patch has proven to be a safe and effective treatment, comparable to topical corticosteroids, after 8 weeks of use. Its sustained-release properties, along with once-daily use, can improve patient satisfaction and promote greater adherence to the treatment. TRIAL REGISTRATION: This study was registered with the Thai Clinical Trials Registry (www. CLINICALTRIALS: in.th) under registration number TCTR20220413003.

Glucocorticoid Nanoparticles Show Full Therapeutic Efficacy in a Mouse Model of Acute Lung Injury and Concomitantly Reduce Adverse Effects.

Glucocorticoids (GCs) are widely used to treat inflammatory disorders such as acute lung injury (ALI). Here, we explored inorganic-organic hybrid nanoparticles (IOH-NPs) as a new delivery vehicle for GCs in a mouse model of ALI. Betamethasone (BMZ) encapsulated into IOH-NPs (BNPs) ameliorated the massive infiltration of neutrophils into the airways with a similar efficacy as the free drug. This was accompanied by a potent inhibition of pulmonary gene expression and secretion of pro-inflammatory mediators, whereas the alveolar-capillary barrier integrity was only restored by BMZ in its traditional form. Experiments with genetically engineered mice identified myeloid cells and alveolar type II (AT II) cells as essential targets of BNPs in ALI therapy, confirming their high cell-type specificity. Consequently, adverse effects were reduced when using IOH-NPs for GC delivery. BNPs did not alter T and B cell numbers in the blood and also prevented the induction of muscle atrophy after three days of treatment. Collectively, our data suggest that IOH-NPs target GCs to myeloid and AT II cells, resulting in full therapeutic efficacy in the treatment of ALI while being associated with reduced adverse effects.