INDUCTION OF PARTURITION IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS).

A 27-yr-old female pygmy hippopotamus (Choeropsis liberiensis) had two consecutive stillbirths with no overt signs of labor, suggestive of uterine inertia. After a third pregnancy was confirmed, an induction protocol was developed. Cloprostenol and betamethasone were administered on d 200 of gestation (time 0 h). Additional doses of cloprostenol were administered at 24 and 48 h and oxytocin at 30, 31, and 48 h. Each injection resulted in preparturient behavior without overt evidence of contractions. Fetal membranes presented at the vulva at 54.5 h after initial cloprostenol and betamethasone administration with no progression of labor. Transvaginal palpation and manual delivery of a live calf followed. Despite confirmed nursing, the serum glutaraldehyde coagulation test was negative. Failure of passive transfer may have been secondary to the induction protocol. The calf was treated with broad-spectrum antimicrobial agents due to diarrhea, and clinical signs resolved. This clinical brief details the first known induction of parturition in a pygmy hippopotamus, which can serve as the basis for further development of the technique.

The need for assisted ventilation corroborates the effectiveness of antenatal corticosteroid therapy in preventing premature lamb mortality.

In premature births, deficiency and/or inactivation of surfactant and incomplete development of lung occur, leading to pulmonary complications and greater need for ventilatory interventions. Prenatal corticosteroid therapy is used to improve neonatal lung function and, thus, may reduce mortality and lower incidence and severity of lung injury. Therefore, this study aimed to assess the need for ventilatory support in preterm lambs subjected or not to prenatal betamethasone treatment, and to evaluate the effectiveness on neonatal survival. Lambing was induced and 13 premature lambs were assigned to Corticosteroid Group (n = 8; lambs from ewes subjected previously to 0.5 mg/kg betamethasone, IM, at 133 days of pregnancy) and Control Group (n = 5; non-treated lambs). Lambs were evaluated for vitality, neurologic reflexes, vital functions and birth weight. Three ventilatory modalities were preconized for critical lambs, according to specific criteria: mask oxygen therapy, self-inflating bag with tracheal tube and mechanical ventilation. Non-treated lambs had lower vitality score, muscle tonus and respiratory rate compared to Corticosteroid Group. Ventilatory support was needed for 3 Control lambs and only 1 Corticosteroid neonate. Corticosteroid lamb required significant less time-frame between birth and onset of ventilatory assistance and remained under ventilation for a shorter time. Percentage of ventilated non-treated lambs correlated negatively with birth weight, muscle tone, heart and respiratory rate. In conclusion, antenatal betamethasone treatment reduces the need for ventilatory assistance in premature lambs. Additionally, mortality is low when a protocol for inducing pulmonary maturity (maternal corticosteroid therapy) and/or ventilatory interventions are employed, ensuring the survival of premature lambs.

Effect of utilizing either a self-reported questionnaire or administrative data alone or in combination on the findings of a randomized controlled trial of the long-term effects of antenatal corticosteroids.

INTRODUCTION: A combination of self-reported questionnaire and administrative data could potentially enhance ascertainment of outcomes and alleviate the limitations of both in follow up studies. However, it is uncertain how access to only one of these data sources to assess outcomes impact study findings. Therefore, this study aimed to determine whether the study findings would be altered if the outcomes were assessed by different data sources alone or in combination. METHODS: At 50-year follow-up of participants in a randomized trial, we assessed the effect of antenatal betamethasone exposure on the diagnosis of diabetes, pre-diabetes, hyperlipidemia, hypertension, mental health disorders, and asthma using a self-reported questionnaire, administrative data, a combination of both, or any data source, with or without adjudication by an expert panel of five clinicians. Differences between relative risks derived from each data source were calculated using the Bland-Altman approach. RESULTS: There were 424 participants (46% of those eligible, aged 49 years, SD 1, 50% male). There were no differences in study outcomes between participants exposed to betamethasone and those exposed to placebo when the outcomes were assessed using different data sources. When compared to the study findings determined using adjudicated outcomes, the mean difference (limits of agreement) in relative risks derived from other data sources were: self-reported questionnaires 0.02 (-0.35 to 0.40), administrative data 0.06 (-0.32 to 0.44), both questionnaire and administrative data 0.01 (-0.41 to 0.43), and any data source, 0.01 (-0.08 to 0.10). CONCLUSION: Utilizing a self-reported questionnaire, administrative data, both questionnaire and administrative data, or any of these sources for assessing study outcomes had no impact on the study findings compared with when study outcomes were assessed using adjudicated outcomes.

Dual-wavelength dye laser combined with betamethasone injection for treatment of keloids: protocol of a randomised controlled trial.

INTRODUCTION: Keloids, benign fibroproliferative tumours characterised by excessive fibroblast proliferation and over-deposition of extracellular matrix, pose a therapeutic challenge with high recurrence rates. Betamethasone (diprospan) injection (BI) is one of the most common non-invasive therapies for keloids. Pulsed dye laser (PDL) has the function of closing microvessels, which may become one of the auxiliary treatment methods of BI and may enhance its curative effect. Some studies suggest that the combination of a dual-wavelength dye laser (DWL) and BI may offer superior efficacy. This randomised controlled trial aims to evaluate whether the combined therapy of DWL+BI outperforms BI alone in treating keloids. METHODS AND ANALYSIS: This single-centre, parallel positive control, randomised trial evaluates the efficacy and safety of DWL (585 nm PDL+1064 nm neodymium-doped yttrium aluminium garnet) combined with BI for keloid treatment. Enrolling 66 adult patients, participants are randomised into DWL+BI or BI groups in a 1:1 ratio. Over 12 weeks, each group undergoes four treatment sessions, ensuring blinding for outcome assessors. Data collection occurs at multiple time points (4, 12, 24 and 52 weeks), with primary outcomes assessing the Vancouver Scar Scale (VSS) improvement rate 24 weeks after the last intervention. Secondary outcomes include VSS improvement rates, changes in keloid volume, changes in relative perfusion index measured by laser speckle contrast imaging, Patient and Observer Scar Assessment Scale results and patient satisfaction. Safety assessments include vital signs, laboratory tests, pregnancy tests and self-reports of adverse reactions. ETHICS AND DISSEMINATION: The results will be presented in peer-reviewed journals and at international conferences. This study is approved by the Ethics Committee of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register (ChiCTR2400080148).

Comparison of the therapeutic effects of photodynamic therapy, transpupillary thermotherapy, and their combination on circumscribed choroidal haemangioma.

OBJECTIVE: To characterize the clinical and imaging features of circumscribed choroidal hemangioma (CCH), and to evaluate individualized treatment efficiency of photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or their combination, followed by retrobulbar injection of betamethasone on CCH resolvement. METHODS: Forty-nine patients with CCHs who underwent PDT, TTT or PDT+TTT treatments were retrospectively analyzed. Their treatment efficacy was compared by analyzing the change of best corrected visual acuity (BCVA), subretinal fluid (SRF) and CCH lesion characteristics. RESULTS: PDT, TTT and PDT+TTT were respectively administrated in 17, 11 and 21 patients. No significant difference in age, gender, affected eyes and tumor location across the three groups. Baseline BCVA were 0.41 ± 0.28, 0.62 ± 0.30 and 0.24 ± 0.24 for PDT, TTT and PDT+TTT groups, respectively (F = 6.572, P = 0.003). CCH treated by three strategies showed significant difference in maximum tumor basal diameter, SRF areas and macula involvement prior to the treatment (P < 0.05). Patients receiving PDT+TTT exhibited larger tumor basal diameter, more SRF, higher ratio of macular involvement than other groups. A total of 38 (77.6 %) cases had good visual acidity with final BCVA ≥0.5 after treatments. PDT and PDT+TTT treatment groups acquired more vision improvement (0.27 ± 0.23 and 0.31 ± 0.26) in BCVA than TTT group (0.09 ± 0.13). All SRF were resolved within two weeks of treatment and no recurrent SRF were found. CONCLUSION: The three treatments showed good performance in improving visual function and controlling SRF, and individualized treatment should be selected primarily by the tumor location, and then the tumor size and presence of SRF.

Clotrimazole-Betamethasone Dipropionate Prescribing for Nonfungal Skin Conditions.

This cross-sectional study identifies the common diagnoses and physician encounter types associated with clotrimazole-betamethasone dipropionate prescriptions among Medicare enrollees in 2021.

Real-world use, perception, satisfaction, and adherence of calcipotriol and betamethasone dipropionate PAD-cream in patients with plaque psoriasis in Spain and Germany: results from a cross-sectional, online survey.

BACKGROUND: Psoriasis significantly impacts patients' quality of life (QoL). Dissatisfaction and non-adherence are major barriers associated with topical treatments. A cream based on the polyaphron dispersion (PAD) Technology containing a fixed-dose of calcipotriol (CAL) and betamethasone dipropionate (BDP) was designed for a patient-friendly psoriasis management. The CAL/BDP PAD-cream demonstrated efficacy, convenience, and safety/tolerability in clinical trials. OBJECTIVES: This research assesses the real-world use, perception, satisfaction, and adherence of CAL/BDP PAD-cream among plaque psoriasis patients. METHODS: Between September-November 2023, psoriasis patients from Spain and Germany using or having used CAL/BDP PAD-cream for >2 weeks were recruited via Wefight network to complete a 30-questions online survey. Anonymized results were pooled for descriptive statistical analysis. RESULTS: The survey was completed by 129 patients (mean age: 43 years; 66% females; mean psoriasis duration: 12 years). Most patients (93%) were satisfied with CAL/BDP PAD-cream. The 66% reported high adherence (visual analogue scale 80-100) and 91% preferred CAL/BDP PAD-cream to their previous topical(s). Patients highlighted its ease/convenience of application, tolerability, and lack of itching/burning. CONCLUSIONS: Psoriasis patients treated with CAL/BDP PAD-cream in a real-world setting show high satisfaction, good adherence, and a positive perception of the product, suggesting that favorable outcomes observed in clinical trials translate to real clinical practice.

Efficacy of Medical Ozone for Treatment of Chronic Musculoskeletal Pain with Abnormal Mitochondrial Redox State: Prospective Randomized Clinical Trial.

BACKGROUND: Chronic primary musculoskeletal pain is multifaceted and 20% of the adult population lives with severe chronic pain and experience symptoms such as intense pain, depression, weakness, sleep problems, decreased quality of life and decreased emotional well-being. OBJECTIVES: This paper studies the efficacy of trigger point injections with ozone compared to standard steroid injection or combination therapy for the treatment of chronic musculoskeletal pain in patients with abnormal mitochondrial redox state. STUDY DESIGN: This is a prospective randomized clinical study conducted with 51 patients experiencing chronic musculoskeletal pain. SETTING: Medical Research Institute Hospital, Alexandria University. METHODS: By computer-generated random numbers the 51 patients were divided into 3 groups. Group A (17 patients) received ozone injection, group B (17 patients) received betamethasone injection and group C (17 patients) received combined ozone and betamethasone injections. The groups were compared based on the intensity of pain and correction of mitochondrial redox state of the patients. RESULTS: Three days after intervention, the visual analog scale (VAS) scores reported by patients were lower in group A compared to group B (with a mean difference 1.27, 95% confidence interval (CI) of 0.15-2.39 (P < 0.02). One and 3 weeks after intervention, VAS scores of patients were lower in groups A and C compared to group B. At one week the mean difference between A and B was 1.2, with a 95% CI of 0.15-2.25 (P < 0.02) and the mean difference between C and B was 1.73 with a 95% CI of 0.69-2.78 (P < 0.001). At 3 weeks the mean difference between A and B was 1.5 with a 95% CI of 0.2-2.87 (P < 0.01) and the mean difference between C and B was 2.27 with a 95% CI of 0.93-3.60 (P < 0.0001). The reduced/oxidized glutathione ratio after intervention was higher in groups A and C compared to group B (P > 0.008). The mitochondrial copy number was higher in group A compared to group B (P < 0.002). LIMITATION: This study didn't allow for the comparison of the experimental groups with a placebo or control group for musculoskeletal pain conditions in orderto establish the role of an abnormal mitochondrial redox state on the pathogenesis of patients from an ethical view. CONCLUSIONS: Ozone therapy or combined ozone and betamethasone treatment are  effective techniques for management of pain since it produced a significant reduction of muscle pain and increase of the pain free interval experienced by patients. Ozone therapy causes pain improvement which increases with time and it improves muscle oxygenation and mitochondrial function. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Medical Research Institute (IORH: IOR 00088812) and was registered at the Pan African Clinical Trial Registry (www.pactr.org) under the identification number PACTR201908620943471. The registration this experiment started on 07/08/2019. This study's protocol followed the CONSORT guidelines and was performed under the relevant guidelines.

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids: The ALPS Follow-Up Study.

Importance: The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. Objective: To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Design, Setting, and Participants: Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Exposure: Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. Main Outcome and Measures: The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Results: Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. Conclusion and Relevance: In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

Reporte de caso de dengue clásico a predominio de sintomatología dermatológica en el marco de la epidemia en la provincia de Misiones 2023-2024 / Case of classic dengue with predominance of dermatologic symptoms in the 2023-2024 epidemic in the province of Misiones

Se presenta un caso femenino de dengue clásico (DC) en el marco de la epidemia 2023-2024 en la provincia de Misiones, con predominio de síntomas dermatológicos de exantemas máculo papulosos, habonosos y eritrodérmicos sobre los síntomas sindrómicos cardinales. Las lesiones presentan componente humoral y de extravasación, sin diátesis ni componentes purpúricos apreciables, presentando una rápida y efectiva evolución al eritema y la normalización con tratamiento antihistamínico y corticoide parenteral. De la misma manera se evalúan alteraciones analíticas hematológicas y hepáticas de gran magnitud, con escasa repercusión clínica, que se mensuran en función del riesgo relativo al dengue hemorrágico (DH) y el pronóstico de la paciente. (AU)

A female case of classic dengue (DC) is presented in the context of the 2023-2024 epidemic in the province of Misiones, with a predominance of dermatologic symptoms of maculopapular, hives, and erythrodermic rashes overlapping the cardinal syndromic symptoms. The lesions have a humoral and extravasation component, without any significant diathesis or purpuric components, showing rapid and effective progression to erythema and normalization with antihistamine and parenteral corticosteroid treatment. Similarly, hematologic and hepatic analytical alterations of great magnitude are evaluated, with little clinical impact, measured in terms of relative risk for hemorrhagic dengue (HD) and the prognosis of the patient. (AU)

Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. OBJECTIVE: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. STUDY DESIGN: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. RESULTS: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.

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.

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.

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 child with Winchester syndrome responding to oral betamethasone and methotrexate.

Winchester syndrome (WS) is a rare genetic disorder with a handful of cases reported to date. We report a 14-year-old male who presented with growth retardation, contracture of left lower limb due to thick indurated skin, hypertrichosis, and bilateral corneal opacity. There was complete improvement in joint contracture with oral betamethasone pulse and weekly oral methotrexate.

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.