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1.
Cureus ; 16(3): e56094, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618469

RESUMO

Optic neuritis (ON) is a debilitating condition that through various mechanisms, including inflammation or demyelination of the optic nerve, can result in partial or total permanent vision loss if left untreated. Accurate diagnosis and promptly initiated treatment are imperative related to the potential of permanent loss of vision if left untreated, which can lead to a significant reduction in the quality of life in affected patients. ON is subtyped as "typical" or "atypical" based on underlying causative etiology. The etiology of ON can be differentiated when appropriate diagnostic testing is performed. Using history taking, neuroimaging, and visual testing to localize the underlying pathology of ON in a time-sensitive manner is critical in mitigating these unsatisfactory outcomes. Herein, we examine the differences in presentation, pathophysiology, and treatments of typical ON causes, like multiple sclerosis (MS), and atypical causes such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) ON. The present investigation places focus on both neuroimaging and visual imaging in the differentiation of ON. Additionally, this review presents physicians with a better understanding of different presentations, treatments, and prognoses of ON.

2.
JMIR Med Inform ; 12: e56572, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630536

RESUMO

Inhaled corticosteroid (ICS) is a mainstay treatment for controlling asthma and preventing exacerbations in patients with persistent asthma. Many types of ICS drugs are used, either alone or in combination with other controller medications. Despite the widespread use of ICSs, asthma control remains suboptimal in many people with asthma. Suboptimal control leads to recurrent exacerbations, causes frequent ER visits and inpatient stays, and is due to multiple factors. One such factor is the inappropriate ICS choice for the patient. While many interventions targeting other factors exist, less attention is given to inappropriate ICS choice. Asthma is a heterogeneous disease with variable underlying inflammations and biomarkers. Up to 50% of people with asthma exhibit some degree of resistance or insensitivity to certain ICSs due to genetic variations in ICS metabolizing enzymes, leading to variable responses to ICSs. Yet, ICS choice, especially in the primary care setting, is often not tailored to the patient's characteristics. Instead, ICS choice is largely by trial and error and often dictated by insurance reimbursement, organizational prescribing policies, or cost, leading to a one-size-fits-all approach with many patients not achieving optimal control. There is a pressing need for a decision support tool that can predict an effective ICS at the point of care and guide providers to select the ICS that will most likely and quickly ease patient symptoms and improve asthma control. To date, no such tool exists. Predicting which patient will respond well to which ICS is the first step toward developing such a tool. However, no study has predicted ICS response, forming a gap. While the biologic heterogeneity of asthma is vast, few, if any, biomarkers and genotypes can be used to systematically profile all patients with asthma and predict ICS response. As endotyping or genotyping all patients is infeasible, readily available electronic health record data collected during clinical care offer a low-cost, reliable, and more holistic way to profile all patients. In this paper, we point out the need for developing a decision support tool to guide ICS selection and the gap in fulfilling the need. Then we outline an approach to close this gap via creating a machine learning model and applying causal inference to predict a patient's ICS response in the next year based on the patient's characteristics. The model uses electronic health record data to characterize all patients and extract patterns that could mirror endotype or genotype. This paper supplies a roadmap for future research, with the eventual goal of shifting asthma care from one-size-fits-all to personalized care, improve outcomes, and save health care resources.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38613642

RESUMO

INTRODUCTION: Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week 32. METHODS: An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA 3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics-age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index-of patients treated with dupilumab. Week 32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA 0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). RESULTS: After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week 32 (IGA 0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (- 12.1 vs - 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. CONCLUSION: The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32 weeks of therapy.

4.
Diagnostics (Basel) ; 14(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611605

RESUMO

Erosive oral lichen planus (EOLP) represents a significant challenge in dental and medical management due to its chronic inflammatory nature, painful symptoms, and impact on quality of life. This study aims to evaluate the current diagnostic approach with novel non-invasive techniques, such as dermoscopy, and also the landscape of treatment options for EOLP, focusing on its efficacy, safety, and the challenges that it present in clinical practice. Through a comprehensive literature review, we explored the use of topical corticosteroids, systemic immunosuppressants, biologics, and Janus kinase (JAK) inhibitors in treating EOLP, alongside examining patient compliance, psychological impacts, and the risk of adverse effects and recurrence. Our findings reveal that while topical corticosteroids are the cornerstone of EOLP treatment, offering symptomatic relief, their long-term use is limited by side effects and tolerance development. Systemic therapies and biologics provide alternatives for refractory cases but necessitate careful adverse effect monitoring. JAK inhibitors show promise as an innovative treatment avenue but require more evidence on long-term safety and efficacy. This study highlights the necessity of personalized treatment approaches due to the variable disease course and response to treatment, underscoring the importance of a multidisciplinary strategy in managing EOLP. The complexity of EOLP treatment, compounded by its psychological and quality of life impacts, demands ongoing research into targeted therapies, the establishment of standardized treatment protocols, and the development of effective outcome measures to improve patient care and treatment outcomes.

5.
Curr Top Med Chem ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38561615

RESUMO

Several classes of compounds are applied in clinics due to their immunosuppressive properties in transplantology and the treatment of autoimmune diseases. Derivatives of mycophenolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. However, improved synthetic approaches of known drugs and novel derivatives are still being reported to attempt better accessibility and therapeutic properties. In this review article, we present the synthesis of the designed chemical structures based on recent literature reports concerning novel compounds as promising immunosuppressive drugs. Moreover, some of the discussed derivers revealed also other types of activities with prospective medicinal potential.

6.
Crit Care Explor ; 6(4): e1071, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38567382

RESUMO

OBJECTIVES: We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness. DATA SOURCES: We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials. STUDY SELECTION: We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP. DATA EXTRACTION: We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness. DATA SYNTHESIS: We included 47 RCTs (n = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty). CONCLUSIONS: In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness.

7.
Tunis Med ; 102(2): 74-77, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38567471

RESUMO

INTRODUCTION: Pemphigus is a therapeutically challenging disease with high morbidity and economic burden. First-line prescription of rituximab remains limited in Tunisia due to its high cost. Systemic steroids remain the standard of care but are associated with a major risk of morbidities and higher treatment costs. AIM: To assess the direct medical costs of pemphigus in Tunisia. METHODS: Retrospective estimation of direct medical costs during the 18 months following the diagnosis using the "bottom-up approach" in the Dermatology Department of Hedi Chaker Hospital, Sfax, Tunisia. RESULTS: Total medical costs were estimated at 38745.7 €, with an average cost of 1 210 € per patient and per year: paraclinical investigations (46%), medical treatment (30%), hospitalization (21%) and outpatient visits (3%). The average cost was the highest in the age group of 15-24 years (1553 €). Treatment costs related to corticosteroid-induced morbidity were estimated at 1208 €. CONCLUSIONS: The management of pemphigus in Tunisia needs to be adapted to take into account the health economic analysis in order to reduce overall disease costs and the burden of steroid-induced morbidities.


Assuntos
Pênfigo , Humanos , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Pênfigo/epidemiologia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Hospitalização
9.
Lupus ; : 9612033241247358, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607271

RESUMO

Idiopathic intracranial hypertension (IIH) is a diagnosis of exclusion characterized by features of raised intracranial pressure (ICP) in the absence of brain parenchymal lesion, vascular malformations, hydrocephalus, or central nervous system (CNS) infection. Commonly used other terms for this entity include benign intracranial hypertension (BIH) or pseudotumor cerebri. Few case reports of systemic lupus erythematosus (SLE) presenting as IIH are available in the literature. We report a 12-year-old girl presented with chronic holocranial headache and occasional episodes of projectile vomiting for the last 6 months and then developed blurring of vision for the last month. She fulfilled the criteria for IIH. Subsequent evaluation revealed a diagnosis of SLE. The occurrence of IIH in SLE is not coincidental and is reported in 1%-5.4% of patients with SLE. Though corticosteroids have not been widely used in IIH, underlying SLE warranted administering corticosteroids with subsequent complete resolution of IIH. Pediatricians, neurologists, intensivists, and ophthalmologists should consider SLE as a differential diagnosis in children presenting with IIH.

11.
Clin Transl Oncol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594379

RESUMO

Radiation-induced skin damage (RID) is the most prevalent, significant side effect of radiotherapy (RT). Nearly 95% of patients experience moderate to severe skin reactions after receiving radiation therapy. However, criteria for acute radiation dermatitis (ARD) treatment remain unavailable. Topical agents with anti-inflammatory properties may protect the skin and facilitate tissue regeneration in patients with RID. Many of these topical agents function through nuclear factor kappa B pathway regulation. They either reduce the levels of inflammatory factors or elicit anti-inflammatory properties of their own, thus preventing oxidative stress and inflammatory responses and thus enabling RID prevention and management. Herein, we explore the 25 topical agents investigated for RID prevention and management thus far and evaluate their mechanisms of action. These agents include 11 natural agents, 3 miscellaneous agents, 9 topical nonsteroidal agents, and 2 topical corticosteroids.

12.
Cureus ; 16(3): e55670, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586706

RESUMO

Erdheim-Chester disease (ECD) is a rare inflammatory myeloid neoplasm affecting multiple systems and organs. The patient is a 38-year-old male with ECD complicated with pulmonary and cutaneous manifestations but without bone lesions diagnosed in 2008. Initial treatment with oral and inhaled corticosteroids achieved persistent favorable disease remission. However, atypical late-onset bone lesions developed in the bilateral femur in 2021. Although BRAF-V600E mutation was negative in the lung specimen at diagnosis, the next-generation gene sequence using biopsied bone lesions revealed a rare BRAF-AGAP3 fusion, leading to the administration of trametinib. This is the first report describing ECD harboring BRAF-AGAP3 fusion successfully treated with trametinib. Our case presents a unique clinical course in which late-onset osteolytic bone lesions developed despite a long-term stabilization of pulmonary lesions with low-dose oral and inhaled corticosteroids.

13.
Am J Obstet Gynecol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588964

RESUMO

BACKGROUND: The recent paradigm shift of treating individuals at risk of late preterm birth with antenatal corticosteroids warrants an assessment of the effect of single dosage. OBJECTIVE: To compare outcomes of neonates born in the late preterm period (34.0-36.6 weeks) following a single dose of antenatal corticosteroids versus placebo. STUDY DESIGN: We performed a secondary analysis of the Antenatal Late Preterm Steroids (ALPS) trial (Gyamfi-Bannerman C. et al.). All individuals enrolled in the parent trial who received only a single dose of either antenatal corticosteroids or placebo and delivered within 24 hours were included. Primary outcome was a composite of respiratory support at 72 hr., including continuous positive airway pressure or high flow nasal cannula ≥ 2 h, oxygen with an inspired fraction of ≥ 30% for ≥ 4 h, or mechanical ventilation. RESULTS: Of the 2,831 individuals in the parent trial, 1,083 (38.3%) met inclusion criteria; of them, 539 (49.8%) received a single dose of antenatal corticosteroids and 544 (50.2%) a single placebo dose. The placebo and antenatal corticosteroids groups had similar demographic and clinical characteristics. There was no difference in the rate of the primary respiratory outcome (aRR 1.12, 95% CI 0.85-1.47) or in the rate of respiratory distress syndrome (aRR 1.47, 95% CI 0.95-2.26) between those who received a single antenatal corticosteroids dose or placebo. An exploratory stratification by randomization-to-delivery intervals of 12-hour increments also showed no association with lower primary respiratory outcome rates. CONCLUSION: In individuals with late preterm birth pregnancies who received antenatal corticosteroids and delivered before a second dose, there were no differences in neonatal respiratory morbidities compared to placebo.

14.
J Clin Med ; 13(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38592149

RESUMO

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

15.
Cureus ; 16(3): e55867, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38595896

RESUMO

Concurrent tuberculous optic neuritis (ON) and optic perineuritis (OPN) in a patient with human immunodeficiency virus (HIV) is extremely rare. HIV-induced progressive CD4 depletion is associated with an increased risk of tuberculosis (TB), disseminated TB, and death. Early detection and initiation of anti-TB therapy with corticosteroid commencement helps in achieving better visual outcomes. Interestingly, we report a case of concurrent ON and OPN in a patient with HIV-TB co-infection. A 29-year-old lady, a prisoner, with newly diagnosed treatment-naive HIV, presented with acute-onset reduced vision in the left eye for 10 days. It was associated with pain in eye movement and headache. The patient was known to be a drug abuser since the age of 19 years and was a sexual worker. Her CD4 count was 292 cells/mm3.Visual acuity of the right eye was 6/12 with a pinhole of 6/9, and there was no perception of light (NPL) in all four quadrants of the left eye. Relative afferent pupillary defect (RAPD) was positive in the left eye. Both anterior segments were unremarkable. The right eye fundoscopy showed a normal optic disc, while the left eye showed a hyperemic disc. During subsequent follow-up, the patient had reduced right eye vision, and the vision dropped to 6/30 with a pinhole of 6/15. Her erythrocyte sedimentation rate (ESR) was raised to 88 mm/h. The Mantoux test was positive. Chest radiography was normal. MRI of the brain and orbit showed significant enhancement of the right optic nerve and left optic nerve sheath suggesting the diagnosis of right eye ON and left eye OPN secondary to TB. The patient was co-managed with an infectious disease team. She was started on highly active antiretroviral therapy (HAART) treatment (oral Tenvir-EM and efavirenz) upon presentation. Anti-TB therapy was commenced two months later. She was started on the intensive phase of the anti-TB regime followed by the maintenance phase. Oral dexamethasone was given concurrently according to the central nervous system (CNS) TB regime for six weeks. During follow-up, her right eye visual acuity was 6/9, and her left eye visual acuity improved to 6/12. Fundoscopy showed bilateral pale discs. To date, no episodes of recurrence have been seen.

16.
World Allergy Organ J ; 17(4): 100896, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576826

RESUMO

Background: Acute allergic reactions (AARs) occur shortly after exposure to an allergen, and the severity is on a continuum. Systemic corticosteroids (CS) are mainstay treatment of moderate to severe AARs, whereas those at risk of the most severe AARs (ie, anaphylaxis) are also recommended prescription of epinephrine autoinjectors. There is limited research on the impact of AARs not fulfilling the criteria for anaphylaxis. We have characterized a sample with a history of moderate to severe AARs and evaluated their self-reported disease burden (ie, daily life impact, anxiety, and treatment impediments). Methods: Survey study of adults with experience of AARs treated with CS. Participants recruited from a web-based panel and using social media were asked to complete a questionnaire related to their allergy and experience of AARs. The results were summarized for the whole sample and across subgroups with and without prescription of epinephrine. Results: The final study sample included 387 participants (80% women, mean age 41), of which 129 (33%) had at some point been prescribed epinephrine. The most common symptoms were respiratory (80%) and skin (78%) manifestations, and the mean (standard deviation, SD) self-rated severity score (scale from 0 [very mild] to 10 [very severe]) of the most recent AAR was 6.1 (2.0). More than 80% had experience of AARs interrupting daily activities and 50% of AARs that had limited work/studies or participation in leisure activities. Most of the respondents reported some degree of anxiety related to AARs and 43% had feared for their lives. Moreover, difficulties swallowing allergy medicine at an AAR was experienced by 26% and not having the medicine available when needed by 66%. Participants with prescription of epinephrine experienced more severe AARs than those without such prescription (mean [SD] severity 6.8 [2.1] vs 5.8 [1.8], p < 0.0001); however, also those without epinephrine prescription reported considerable anxiety and impact on daily life and to a similar degree as those with prescription. Conclusions: In this sample, subjects with experience of AARs treated with CS showed a considerable disease burden with anxiety and interruption on daily life, as well as problems related to access to, and swallowing of, medication. Although respondents with epinephrine prescription had more severe disease, a high disease burden was also evident among those without epinephrine. The study increases the knowledge of people with moderate to severe AARs, a patient population that has previously been underrepresented in the research literature.

17.
Ann Med Surg (Lond) ; 86(4): 2200-2203, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576936

RESUMO

Introduction and importance: Churg-Strauss syndrome (CSS) is a rare multisystemic condition characterized by asthma, blood and tissue eosinophilia, and vasculitis. The purpose of this work is to present a detailed overview of CSS, focusing on its epidemiology, clinical symptoms, histological criteria, gastrointestinal involvement, and therapy. Case presentation: The authors report a case of a 40-year-old woman with CSS who had peripheral eosinophilia, small vessel vasculitis, and bronchial asthma. Diagnosed with symmetric polyarthritis six months ago, experienced abdominal pain, vomiting, and loose faeces. Diagnostic tests revealed CSS with systemic involvement. In addition, we undertake a literature analysis to emphasize essential elements of CSS, such as its rarity and the difficulties in diagnosing and managing it. Clinical discussion: CSS can cause gastrointestinal symptoms including stomach pain, diarrhoea, mucosal ulcers, rectal bleeding, and bowel perforations. Corticosteroids and immunosuppressives are routinely used in treatment, with caution due to the risks of long-term steroid use. The goal of treatment should be to induce remission while minimizing side effects. Conclusion: CSS is a rare condition, with an annual incidence of 2.4 per million and a prevalence of 1.3 per 100 000. The illness typically presents with necrotizing vasculitis, extravascular granulomas, and eosinophilic tissue infiltration. CSS is a complex and rare condition that requires high clinical suspicion, especially when patients present with gastrointestinal symptoms in addition to asthma and eosinophilia. This case study adds to our understanding of CSS and emphasizes the significance of a holistic strategy for its management.

18.
Exp Eye Res ; : 109902, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641196

RESUMO

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need. Herein, we aim to explore the sustained effect of Dexamethasone sodium phosphate (DSP)-loaded polymeric nanoparticles (PLGA-DSP-NP) following a single subconjunctival injection in the management and prevention of corneal injury progression upon exposure to NM. DSP is an FDA approved corticosteroid with proven anti-inflammatory properties. We formulated PLGA-DSP-NP with zinc chelation ion bridging method using PLGA polymer, with particles of approximately 250 nm and a drug loading of 6.5 wt%. Under in vitro sink conditions, PLGA-DSP-NP exhibited a sustained drug release for two weeks. Notably, in NM injured cornea, a single subconjunctival (SCT) injection of PLGA-DSP-NP outperformed DSP eyedrops (0.1%), DSP solution, placebo NP, and saline, significantly mitigating corneal neovascularization, ulceration, and opacity for the two weeks study period. Through PLGA-DSP-NP injection, sustained DSP release hindered inflammatory cytokine recruitment, angiogenic factors, and endothelial cell proliferation in the cornea. This strategy presents a promising localized corticosteroid delivery system to effectively combat NM-induced corneal injury, offering insights into managing vesicant exposure.

19.
BMC Pregnancy Childbirth ; 24(1): 286, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637735

RESUMO

BACKGROUND: To investigate the association between late preterm antenatal corticosteroid treatment and outcome in late preterm neonates born to mothers with gestational diabetes mellitus, METHODS: All patients with gestational diabetes mellitus who had a late preterm delivery at Etlik Lady Zübeyde Hospital between 2017 and 2021 were included. Women who met the inclusion criteria and were not given antenatal corticosteroid treatment during current pregnancy before 34 0/7 weeks of gestation were divided into two groups according to whether or not they received late preterm antenatal corticosteroid treatment. The two groups were compared in terms of adverse neonatal complications. The main outcomes were composite respiratory outcome and composite neonatal outcome. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome. RESULTS: This retrospective cohort study included a total of 400 participants with gestational diabetes mellitus who had a late preterm delivery within the study period. Of these women, 196 (49%) received late preterm antenatal corticosteroid treatment. Main outcomes showed no difference. Decreasing gestational age at birth was identified as an independent risk factor predicting both composite respiratory outcome and composite neonatal outcome in multivariate logistic regression analysis. CONCLUSIONS: Antenatal corticosteroid treatment at or after 34 0/7 weeks of gestation in women with gestational diabetes mellitus who had a late preterm delivery was not associated with improvement in adverse neonatal outcomes. Decreasing gestational age at birth was the only independent risk factor predicting composite neonatal and composite respiratory outcomes.


Assuntos
Diabetes Gestacional , Nascimento Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Gravidez , Feminino , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/induzido quimicamente , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Idade Gestacional , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle
20.
Trials ; 25(1): 258, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609983

RESUMO

BACKGROUND: Preterm birth complications are the leading cause of newborn and under-5 mortality. Over 85% of all preterm births occur in the late preterm period, i.e. between 34 and < 37 weeks of gestation. Antenatal corticosteroids (ACS) prevent mortality and respiratory morbidity when administered to women at high risk of an early preterm birth, i.e. < 34 weeks' gestation. However, the benefits and risks of ACS in the late preterm period are less clear; both guidelines and practices vary between settings. Emerging evidence suggests that the benefits of ACS may be achievable at lower doses than presently used. This trial aims to determine the efficacy and safety of two ACS regimens compared to placebo, when given to women with a high probability of late preterm birth, in hospitals in low-resource countries. METHODS: WHO ACTION III trial is a parallel-group, three-arm, individually randomized, double-blind, placebo-controlled trial of two ACS regimens: dexamethasone phosphate 4 × 6 mg q12h or betamethasone phosphate 4 × 2 mg q 12 h. The trial is being conducted across seven sites in five countries-Bangladesh, India, Kenya, Nigeria, and Pakistan. Eligible women are those with a gestational age between 34 weeks 0 days and 36 weeks 5 days, who have a high probability of preterm birth between 12 h and 7 days (up to 36 weeks 6 days gestation). The primary outcome is a composite of stillbirth or neonatal death within 72 h of birth or use of newborn respiratory support within 72 h of birth or prior to discharge from hospital, whichever is earlier. Secondary outcomes include safety and health utilization measures for both women and newborns. The sample size is 13,500 women. DISCUSSION: This trial will evaluate the benefits and possible harms of ACS when used in women likely to have a late preterm birth. It will also evaluate a lower-dose ACS regimen based on literature from pharmacokinetic studies. The results of this trial will provide robust critical evidence on the safe and appropriate use of ACS in the late preterm period internationally. TRIAL REGISTRATION: ISRCTN11434567 . Registered on 7 June 2021.


Assuntos
Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Nascimento Prematuro/prevenção & controle , Corticosteroides/efeitos adversos , Método Duplo-Cego , Hospitais , Probabilidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
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