Endoscopic Dilatation with Ultrathin Endoscope Assisted Method for Esophageal and Pyloric Stricture related Corrosive Injury: 4 Years Case Series Study.

Corrosive injuries (CI) become medical problems related complications include esophageal, pyloric stricture and squamous cell carcinoma, physical and quality of life. Endoscopic (ED) dilatation is primary therapy. The ultrathin endoscope-assisted method is potentially safe and useful in avoiding technical failure. Describe clinical outcomes of ED ED-related CI including successful, refractory, recurrent, and complications-related procedures. Case series study of esophageal and/or pyloric stricture patients after CI who underwent dilatation at Soetomo General Hospital (July 2018 - July 2022). One - biweekly ED using Through The Scope (TTS) balloon or Savary Bougie dilator. The target diameter is 14mm. Fifteen patients with stricture-related CI. Eleven patients underwent ED with a total of 73 procedures. Mean age 31,45 years, predominantly male patients (6), suicide attempt (7), acid agent (9), located at esophagus (3), pylorus (3), or both (5). Number of esophageal dilatation to achieve the target of 14 mm was 1-2 and 2-15 procedures for simple and complex stricture. Five esophageal strictures were successfully dilated but 2 patients were recurrent and 3 cases were refractory to ED. Pyloric dilatation resulted in a lower success rate. Recurrent and refractory cases were 5 and 3 patients respectively. ED with ultrathin endoscope method is useful for traversing guidewire during ED. Ongoing inflammation and fibrosis were linked to recurrent and refractory stricture.

Scleral Contact Lens to Preserve a Corneal Graft in Chronic Lagophthalmos.

Facial burns involving the periorbital region may lead to cicatricial ectropion and lagophthalmos, causing severe exposure keratopathy and eventually blindness if uncorrected. In these patients, it is critical to provide aesthetic and functional surgical correction to protect the ocular surface from chronic desiccation in addition to visual rehabilitation. Conventional methods may not be sufficient to provide visual rehabilitation in complex cases. Scleral lenses can be a multipurpose alternative for these patients. Herein, we present the challenging case of a patient who developed cicatricial lagophthalmos and exposure keratopathy after facial transplantation due to gasoline burns and received a scleral contact lens for visual rehabilitation.

URP20 improves corneal injury caused by alkali burns combined with pathogenic bacterial infection in rats.

Corneal alkali burns often occur in industrial production and daily life, combined with infection, and may cause severe eye disease. Oxidative stress and neovascularization (NV) are important factors leading to a poor prognosis. URP20 is an antimicrobial peptide that has been proven to treat bacterial keratitis in rats through antibacterial and anti-NV effects. Therefore, in this study, the protective effect and influence mechanism of URP20 were explored in a rat model of alkali burn together with pathogenic bacteria (Staphylococcus aureus and Escherichia coli) infection. In addition, human umbilical vein endothelial cells (HUVECs) and human corneal epithelial cells (HCECs) were selected to verify the effects of URP20 on vascularization and oxidative stress. The results showed that URP20 treatment could protect corneal tissue, reduce corneal turbidity, and reduce the NV pathological score. Furthermore, URP20 significantly inhibited the expression of the vascularization marker proteins VEGFR2 and CD31. URP20 also reduced the migration ability of HUVECs. In terms of oxidative stress, URP20 significantly upregulated SOD and GSH contents in corneal tissue and HCECs (treated with 200 µM H2O2) and promoted the expression of the antioxidant protein Nrf2/HO-1. At the same time, MDA and ROS levels were also inhibited. In conclusion, URP20 could improve corneal injury combined with bacterial infection in rats caused by alkali burns through antibacterial, anti-NV, and antioxidant activities.

[Histological evaluation of esophageal stricture in children with caustic burn]. / Patogistologicheskaya kharakteristika striktury pishchevoda pri kausticheskom ozhoge u detei.

OBJECTIVE: To analyze histological features of esophageal strictures in children with chemical burn following ingestion of household products containing sodium (potassium) hypochlorite, sodium (potassium) hydroxide. MATERIAL AND METHODS: We analyzed 3 children with complicated caustic esophageal burns. Children at the time of swallowing the caustic were 26.3±4.1 months. Multiple dilatations of esophageal stricture were ineffective. Therefore, extirpation or subtotal resection of the esophagus and esophagocoloplasty were performed. We stained specimens using hematoxylin and eosin, as well as Masson's trichrome. RESULTS: Severe esophageal burns caused by sodium (potassium) hydroxide and/or sodium hypochlorite are followed by irreversible tissue lesions and non-dilatable stricture. Strictures are localized in the areas of physiological narrowing of the esophagus. The longest stricture follows ingestion of liquid substance. Histological properties include atrophy of glands and mucous membrane, muscle layer substitution by connective tissue and diffuse sclerosis of esophageal wall. CONCLUSION: Non-dilatable esophageal stricture following caustic burn in children is due to irreversible morphological lesion of esophageal wall with mucous layer atrophy and sclerosis of all layers.

Self-Medication for Toothache Causing Chemical Burn of Oral Mucosa and Alveolar Bone Loss in a Child.

Chemical burn of the oral mucosa can occur as a result of the inadvertent, intentional or iatrogenic use of chemicals. Self-treatment for toothache relief with nonpharma ceutical substances can result in a chemical burn. A detailed history is paramount in such cases to identify the etiologic agent to proceed with appropriate treatment. The purpose of this report is to describe the case of an eight-year-old with a complaint of toothache who rinsed his mouth with potassium aluminium sulfate solution to achieve pain relief. This caused ulceration of the attached gingiva and oral mucosa and necrosis of the alveolar bone surrounding the offending tooth, leading to its mobility. This case highlights the disastrous consequences of inappropriate self-treatment to achieve pain relief from toothache.

A Mouse Model for Corneal Neovascularization by Alkali Burn.

Corneal neovascularization (CoNV), a pathological form of angiogenesis, involves the growth of blood and lymph vessels into the avascular cornea from the limbus and adversely affects transparency and vision. Alkali burn is one of the most common forms of ocular trauma that leads to CoNV. In this protocol, CoNV is experimentally induced using sodium hydroxide solution in a controlled manner to ensure reproducibility. The alkali burn model is useful for understanding the pathology of CoNV and can be extended to study angiogenesis in general because of the avascularity, transparency, and accessibility of the cornea. In this work, CoNV was analyzed by direct examination under a dissecting microscope and by immunostaining flat-mount corneas using anti-CD31 mAb. Lymphangiogenesis was detected on flat-mount corneas by immunostaining using anti-LYVE-1 mAb. Corneal edema was visualized and quantified using optical coherence tomography (OCT). In summary, this model will help to advance existing neovascularization assays and discover new treatment strategies for pathologic ocular and extraocular angiogenesis.

Complex Refractory Esophageal Stricture Due to Chronic Gasoline Ingestion: A Case Report.

Esophageal stricture is a narrowing of the esophageal lumen which is often characterized by impaired swallowing or dysphagia. It can be induced by inflammation, fibrosis or neoplasia which damages the mucosa and/or submucosa of the esophagus. Corrosive substance ingestion is one of the major causes of esophageal stricture, particularly in children and young adults. For instance, accidental ingestion or attempted suicide with corrosive household products is not uncommon. Gasoline is a liquid mixture of aliphatic hydrocarbons derived from the fractional distillation of petroleum, which is then combined with additives such as isooctane and aromatic hydrocarbons (e.g., toluene and benzene). Gasoline also contains several other additives including ethanol, methanol and formaldehyde, which make it a corrosive agent. Interestingly, to the best of our knowledge, the incidence of esophageal stricture caused by chronic gasoline ingestion has not been reported. In this paper, we report the case of a patient with dysphagia due to complex esophageal stricture due to chronic gasoline ingestion who underwent a series of esophago-gastro-duodenoscopy (EGD) procedures and repeated esophageal dilation.

[The role of endosonography in the treatment of chemical ulcerative-necrotic burns of the esophagus]. / Rol' endosonografii v opredelenii taktiki lecheniya khimicheskogo yazvenno-nekroticheskogo ozhoga pishchevoda: klinicheskoe nablyudenie.

The authors present ultrasonography-assisted endoscopic diagnosis of chemical burn of the esophagus. This method early predicted decompensated cicatricial stenosis of the esophagus that was valuable to determine treatment strategy. Preventive mini-invasive endoscopic percutaneous gastrostomy provided adequate enteral nutrition in a patient with decompensated esophageal stenosis before reconstructive surgery.

Luteolin ameliorates cornea stromal collagen degradation and inflammatory damage in rats with corneal alkali burn.

Corneal alkali burn (AB) is a blindness-causing ocular trauma commonly seen in clinics. An excessive inflammatory reaction and stromal collagen degradation contribute to corneal pathological damage. Luteolin (LUT) has been studied for its anti-inflammatory effects. In this study, the effect of LUT on cornea stromal collagen degradation and inflammatory damage in rats with corneal alkali burn was investigated. After corneal alkali burn, rats were randomly assigned to the AB group and AB + LUT group and received an injection of saline and LUT (200 mg/kg) once daily. Subsequently, corneal opacity, epithelial defects, inflammation and neovascularization (NV) were observed and recorded on Days 1, 2, 3, 7 and 14 post-injury. The concentration of LUT in ocular surface tissues and anterior chamber, as well as the levels of collagen degradation, inflammatory cytokines, matrix metalloproteinases (MMPs) and their activity in the cornea were detected. Human corneal fibroblasts (HCFs) were co-cultured with interleukin (IL)-1ß and LUT. Cell proliferation and apoptosis were assessed by CCK-8 assay and flow cytometry respectively. Measurement of hydroxyproline (HYP) in culture supernatants was used to quantify the amount of collagen degradation. Plasmin activity was also assessed. ELISA or real-time PCR was used to detect the production of matrix metalloproteinases (MMPs), IL-8, IL-6 and monocyte chemotactic protein (MCP)-1. Furthermore, the immunoblot method was used to assess the phosphorylation of mitogen-activated protein kinases (MAPKs), transforming growth factor-ß-activated kinase (TAK)-1, activator protein-1 (AP-1) and inhibitory protein IκB-α. At last, immunofluorescence staining helped to develop nuclear factor (NF)-κB. LUT was detectable in ocular tissues and anterior chamber after intraperitoneal injection. An intraperitoneal injection of LUT ameliorated alkali burn-elicited corneal opacity, corneal epithelial defects, collagen degradation, NV, and the infiltration of inflammatory cells. The mRNA expressions of IL-1ß, IL-6, MCP-1, vascular endothelial growth factor (VEGF)-A, and MMPs in corneal tissue were downregulated by LUT intervention. And its administration reduced the protein levels of IL-1ß, collagenases, and MMP activity. Furthermore, in vitro study showed that LUT inhibited IL-1ß-induced type I collagen degradation and the release of inflammatory cytokines and chemokines by corneal stromal fibroblasts. LUT also inhibited the IL-1ß-induced activation of TAK-1, mitogen-activated protein kinase (MAPK), c-Jun, and NF-κB signaling pathways in these cells. Our results demonstrate that LUT inhibited alkali burn-stimulated collagen breakdown and corneal inflammation, most likely by attenuating the IL-1ß signaling pathway. LUT may therefore prove to be of clinical value for treating corneal alkali burns.

Caustic oesophageal stricture treated by instrumental dilatation: A review of 6 years of practice at the pediatric university hospital charles de gaulle of Ouagadougou.

Background: Oesophageal stricture is one of the most important and redoubtable complications following caustic ingestions in children. Instrumental dilatation is usually considered the first line of treatment. Aims and Objectives: This study aims to evaluate the outcomes of caustic stenosis treatment when using Lerut dilatators. Materials and Methods: This is a descriptive retrospective study from May 2014 to April 2020. All children under 15 years hospitalised in our department for caustic oesophageal stricture and had a gastrostomy and oesophageal dilatation with insertion of an endless wire were included. Results: A total of 83 patients were included. The sex ratio was 2.2. The mean age was 4 years. The mean time from caustic ingestion to presentation was 90 days. Oesophageal stricture was mostly caused by caustic soda (n = 41) and potash (n = 15). We performed in total 469 dilatations and had only three oesophageal perforations. After a mean follow-up of 17 months, we had 60.2% good results (n = 50) and 7.2% (n = 6) failures. The mortality rate was 13.2% (n = 11). Conclusion: The results of the dilations by Lerut dilatators give encouraging results in our department. It is easy to perform and its complications remain rare. Mortality could be reduced by adequate nutritional support.

Procedural and Surgical Interventions for Esophageal Stricture Secondary to Caustic Ingestion in Children.

BACKGROUND: Esophageal injury after caustic ingestion can vary in severity and may result in significant long-term morbidity due to stricture development. The optimal management remains unknown. We aim to determine the incidence of esophageal stricture due to caustic ingestion and quantify current procedural and operative management strategies. METHODS: The Pediatric Health Information System (PHIS) was utilized to identify patients 0-18 years old who experienced caustic ingestion from January 2007-September 2015 and developed subsequent esophageal stricture until December 2021. Post-injury procedural and operative management was identified utilizing ICD-9/10 procedure codes for esophagogastroduodenoscopy (EGD), esophageal dilation, gastrostomy tube placement, fundoplication, tracheostomy, and major esophageal surgery. RESULTS: 1,588 patients from 40 hospitals experienced caustic ingestion of which 56.6% were male, 32.5% non-Hispanic White, and the median age at time of injury was 2.2 years (IQR: 1.4,4.8). Median length of initial admission was 1.0 day (IQR: 1.0, 3.0). 171/1,588 (10.8%) developed esophageal stricture. Among those who developed stricture, 144 (84.2%) underwent at least 1 additional EGD, 138 (80.7%) underwent dilation, 70 (40.9%) underwent gastrostomy tube, 6 (3.5%) underwent fundoplication, 10 (5.8%) underwent tracheostomy, and 40 (23.4%) underwent major esophageal surgery. Patients underwent a median of 9 dilations (IQR 3, 20). Major surgery was performed at a median of 208 (IQR: 74, 480) days after caustic ingestion. CONCLUSION: Many patients with esophageal stricture after caustic ingestion will require multiple procedural interventions and potentially major surgery. These patients may benefit from early multi-disciplinary care coordination and the development of a best-practice treatment algorithm. LEVEL OF EVIDENCE: III.

Salubrinal Ameliorates Inflammation and Neovascularization via the Caspase 3/Enos Signaling in an Alkaline-Induced Rat Corneal Neovascularization Model.

Background and Objectives: Ocular alkaline burn is a clinical emergency that can cause permanent vision loss due to limbal stem cell deficiency and corneal neovascularization (CNV). Although the basic pathogenetic mechanisms are considered to be acute oxidative stress and corneal neovascularization triggered by inflammation, the underlying intracellular mechanisms have not been clearly elucidated. The aim of this study was to investigate the role of endoplasmic reticulum (ER) stress on inflammation and neovascularization, and the effect of the ER stress inhibitor salubrinal (SLB), as a novel treatment in a corneal alkaline burn model in rats. Methods: Chemical burns were created by cautery for 4 s using a rod coated with 75% silver nitrate and 25% potassium nitrate in the corneal center for the corneal neovascularization (CNV) model. Twenty-eight Wistar albino rats were divided into four groups: SHAM, CNV, CNV + SLB, and CNV + bevacizumab (BVC). After the CNV model was applied to the right eye, a single subconjunctival dose (0.05 mL) of 1 mg/kg salubrinal was injected into both eyes in the CNV + SLB group. A total of 1.25 mg/mL of subconjunctival BVC was administered to the CNV + BVC group. Fourteen days after experimental modeling and drug administration, half of the globes were placed in liquid nitrogen and stored at -20 °C until biochemical analysis. The remaining tissues were collected and fixed in 10% buffered formalin for histopathological and immunohistochemical analysis. Three qualitative agents from three different pathways were chosen: TNFR for inflammation, endothelial nitric oxide synthase (e-NOS) for vascular endothelial growth factor (VEGF)-mediated vascular permeability, and caspase-3 for cellular apoptosis. Results: Significantly lower caspase-3 and eNOS levels were detected in the CNV + SLB and CNV + BVC groups than in the CNV group. Additionally, histopathological evaluation revealed a significant decrease in neovascularization, inflammatory cell infiltration, and fibroblast activity in the CNV + SLB and CNV + BVC groups. The endoplasmic reticulum stress inhibitor, salubrinal, administered to the treatment group, attenuated apoptosis (caspase-3) and inflammation (e-NOS). In the control group (left eyes of the SLB group), salubrinal did not have a toxic effect on the healthy corneas. Conclusion: The ER stress pathway plays an important role in angiogenesis after alkaline corneal burns, and treatment with SLB modulates this pathway, reducing caspase-3 and eNOS levels. Further studies are needed to understand the molecular mechanisms altered by SLB-mediated therapy. The fact that more than one mechanism plays a role in the pathogenesis of CNV may require the use of more than one molecule in treatment. SLB has the potential to affect multiple steps in CNV pathogenesis, both in terms of reducing ER stress and regulating cellular homeostasis by inhibiting the core event of integrated stress response (ISR). Therefore, it can be used as a new treatment option and as a strengthening agent for existing treatments. Although blockade of intracellular organelle stress pathways has shown promising results in experimental studies, more in-depth research is needed before it can be used in routine practice. To the best of our knowledge, this study is the first to report the role of ER stress in corneal injury.

Role of tenon advancement in treating limbal ischemia in acute chemical injury.

Background: In acute chemical injury, damage can range from ocular surface epithelial defects to limbal and scleral ischemia. This may subsequently progress to corneal or scleral melting and perforation and finally result in phthisis bulbi. Thus, acute chemical injury is a potentially blinding condition and warrants attention. The accurate technique to assess the damage incurred should be practiced to avoid undertreatment and subsequent complications. Surgical intervention wherever needed should be appropriately timed and should be performed. The primary aim of medical or surgical intervention in acute chemical injury is to attain a stable and epithelized ocular surface. Even a conjunctival phenotype over the cornea is a desirable outcome. Purpose: This video discusses the nuances involved in the assessment and planning of Tenon advancement with amniotic membrane grafting for treating limbal ischemia in acute chemical injury. Synopsis: The video demonstrates the technique of restoration of limbal vascularization by performing Tenon advancement with amniotic membrane grafting and its outcome. Highlights: Ocular surface painting with fluorescein dye is essential to assess the areas of surface involvement. Merely instilling the fluorescein dye in the cul-de-sac will underestimate the extent of the damage. Tenon advancement should ideally be planned between 7 and 10 days following an injury when actual limbal blanching is obvious. A stable and epithelized ocular surface is the desirable outcome irrespective of the epithelial phenotype. Video Link: https://youtu.be/06XhwLKnsIA.

Long-Term Comprehensive Management of Bilateral Limbal Stem Cell Deficiency Secondary to Severe Chemical Burn: 10 Years of Follow-Up.

PURPOSE: To describe the long-term management of bilateral limbal stem cell deficiency secondary to a severe chemical burn. METHODS: Descriptive case report. IMPORTANCE: This case highlights the importance of early intervention in ocular chemical burns for the preservation of tissue integrity and avoidance of perforation. We also review the use of proper ocular surface reconstructive techniques to restore the function of the limbal area, as well as the immunomodulatory strategies and follow-up needed for these interventions.

[Gastric pull-up in caustic stenosis: presentation of a complex clinical case]. / Ascenso gástrico en estenosis por cáusticos: presentación de un caso clínico complejo.

Introduction: Chemical substances are important causes of gastrointestinal tract injuries and usually affect two groups of patients: children under 5 years of age and adults who attempt suicide. Its effects can range from necrosis to perforation of the digestive tract, which can affect the mouth, pharynx, esophagus and stomach. The main complication of accidental caustic ingestion is esophageal stricture. The frequency with which esophageal strictures appear ranges from 15% to 35% and is related to the degree of injury induced by the ingested agent. They may become symptomatic by the second or third week after a latent repair phase or, in other cases, months or years after ingestion. Different forms of treatment have been applied to treat caustic esophageal strictures, and endoscopic dilation is the first line, with successful results in 60% to 80% of patients. If these are not effective, surgical treatment for esophageal replacement is indicated. Clinical Case: A clinical case of a 48-year-old male patient with no chronic degenerative history is presented, who began suffering after accidental ingestion of caustic substance 4 months ago with dysphagia to liquids and solids, for which he is protocolized in our unit for definitive surgical resolution by gastric pull-up. Conclusions: Although associated with high rates of anastomotic stricture, transhiatal esophagectomy and gastric pull-up with cervical anastomosis are safe procedures for the treatment of caustic esophageal strictures.

Introducción: las sustancias químicas son causas importantes de lesiones del tracto gastrointestinal y suelen afectar a dos grupos de pacientes: los niños menores de 5 años y los adultos que intentan el suicidio. Sus efectos pueden variar, desde la necrosis hasta la perforación del tubo digestivo, que puede afectar la boca, faringe, esófago y estómago. La principal complicación de la ingesta accidental de cáusticos es la estenosis esofágica. La frecuencia con la que aparecen las estenosis esofágicas oscila entre el 15 y el 35% y se relaciona con el grado de lesión inducida por el agente ingerido. Pueden hacerse sintomáticas hacia la segunda o tercera semanas después de una fase latente de reparación o, en otros casos, meses o años después de la ingesta. Diferentes formas de tratamiento se han aplicado para tratar las estenosis esofágicas por cáusticos, y en primera línea está la dilatación endoscópica, con resultados exitosos en el 60 a 80% de los pacientes. Si estas no son efectivas se indica el tratamiento quirúrgico de reemplazo esofágico. Caso clínico: se presenta el caso clínico de un paciente masculino de 48 años de edad sin antecedentes crónico-degenerativos, el cual inicia padecimiento tras la ingesta accidental de sustancia cáustica hacía 4 meses, con disfagia a líquidos y sólidos, por lo que es protocolizado en nuestra unidad para resolución quirúrgica definitiva mediante ascenso gástrico. Conclusiones: aunque se asocia con tasas altas de estenosis anastomótica, la esofagectomía transhiatal y el ascenso gástrico con anastomosis cervical son procedimientos seguros para el tratamiento de estenosis esofágicas por sustancias cáusticas.

Scleral contact lenses for optimal visual recovery in a case of severe acid burn with total lagophthalmos.

Chemical injuries can severely damage the ocular surface. We present the case of a man in his 40s with severe periocular chemical injury with total lid loss and severe exposure keratopathy. He sustained burns to 45% of his body surface area and needed tracheostomy and multiple full-thickness skin grafts. Both eyes required surgery, Boston type 1 keratoprosthesis and penetrating keratoplasty for the right and left eye, respectively. There was melting in the right eye and a persistent epithelial defect in the left eye. Eventually, we suggested 18 mm diameter scleral contact lenses for both eyes to aid in ocular surface stabilisation. His best corrected visual acuity improved significantly with the scleral lenses to 20/100 and 20/320 in the right and left eyes, respectively. This case demonstrates that scleral lenses can treat the complications of exposure keratopathy and can improve vision. Therefore, they may be considered for rehabilitation of the ocular surface in eyes with severe chemical periocular injuries.

Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury.

Purpose: To evaluate the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits. Methods: Sixteen New Zealand White rabbits were included. Alkali injuries were produced using 1N sodium hydroxide on a 5-mm diameter Whatman #1 filter paper for 1 minute. Four corneas in each group were treated six times per day for 1 month with 50 µL of (1) 0.8 mg/mL losartan in balanced salt solution (BSS), (2) 1% prednisolone acetate, (3) combined 0.8 mg/mL losartan and 1% prednisolone acetate, or (4) BSS. Area of opacity and total opacity were analyzed in standardized slit-lamp photos with ImageJ. Corneas in both groups were cryofixed in Optimal cutting temperature (OCT) compound at 1 month after surgery, and immunohistochemistry was performed for alpha-smooth muscle actin (α-SMA) and keratocan or transforming growth factor ß1 and collagen type IV with ImageJ quantitation. Results: Combined topical losartan and prednisolone acetate significantly decreased slit-lamp opacity area and intensity, as well as decreased stromal myofibroblast α-SMA area and intensity of staining per section and confined myofibroblasts to only the posterior stroma with repopulation of the anterior and mid-stroma with keratocan-positive keratocytes after 1 month of treatment. Corneal fibroblasts produced collagen type IV not associated with basement membranes, and this production was decreased by topical losartan. Conclusions: Combined topical losartan and prednisolone acetate decreased myofibroblast-associated fibrosis after corneal alkali burns that produced full-thickness injury, including corneal endothelial damage. Increased dosages and duration of treatment may further decrease scarring fibrosis. Translational Relevance: Topical losartan and prednisolone acetate decrease myofibroblast-mediated scarring fibrosis after corneal injury.

Emergency computed tomography evaluation of caustic ingestion.

Computed tomography (CT) is used increasingly for the emergency assessment of caustic injuries and the need for emergency endoscopy has been challenged. The study evaluates outcomes of caustic ingestion in the modern era and the feasibility of abandoning emergency endoscopy. Between 2013 and 2019, 414 patients (197 men, median age 42 years) were admitted for caustic ingestion. Emergency and long-term outcomes of patients managed by CT and endoscopy (n = 120) and by CT alone (n = 294) were compared. Propensity score-based analysis was performed to limit bias of between-group comparison. A standard mortality ratio (SMR) was used to compare the observed mortality with the expected mortality in the general French population. Complications occurred in 97 (23%) patients and 17 (4.1%) patients died within 90 days of ingestion. Among 359 patients who underwent nonoperative management, 51 (14%) experienced complications and 7 (2%) died. Of 55 patients who underwent emergency surgery, 46 (84%) experienced complications and 10 (18%) died. The SMR was 8.4 for whole cohort, 5.5 after nonoperative management, and 19.3 after emergency surgery. On multivariate analysis, intentional ingestion (P < 0.016), age (P < 0.0001) and the CT grade of esophageal injuries (P < 0.0001) were independent predictors of survival. The CT grade of esophageal injuries was the only independent predictor of success (P < 0.0001). Crude and propensity match analysis showed similar survival in patients managed with and without endoscopy. CT evaluation alone can be safely used for the emergency management of caustic ingestion.

AIP1 suppresses neovascularization by inhibiting the NOX4-induced NLRP3/NLRP6 imbalance in a murine corneal alkali burn model.

BACKGROUND: Apoptosis signal-regulating kinase 1-interacting protein 1 (AIP1) participates in inflammatory neovascularization induction. NADPH oxidase 4 (NOX4) produces reactive oxygen species (ROS), leading to an imbalance in nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and NLR family pyrin domain containing 6 (NLRP6) expression. The mechanisms of AIP1, NOX4, ROS and inflammasomes in corneal neovascularization were studied herein. METHODS: C57BL/6 and AIP1-knockout mice were used in this study. The alkali burn procedure was performed on the right eye. Adenovirus encoding AIP1 plus green fluorescence protein (GFP) (Ad-AIP1-GFP) or GFP alone was injected into the right anterior chamber, GLX351322 was applied as a NOX4 inhibitor, and then corneal neovascularization was scored. The expression of related genes was measured by quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining. 2',7'-Dichlorofluorescin diacetate staining was used to determine the ROS levels. RESULTS: The expression of AIP1 was decreased, while that of cleaved interleukin-1ß (clv-IL-1ß) and vascular endothelial growth factor A (VEGFa) was increased after alkali burn injury. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. NLRP3/NLRP6 expression was imbalanced after alkali burns. GLX351322 reversed the imbalance in NLRP3/NLRP6 by reducing the ROS levels. This treatment also reduced the expression of clv-IL-1ß and VEGFa, suppressing neovascularization. CONCLUSIONS: AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burn injury. Based on the pathogenesis of corneal neovascularization, these findings are expected to provide new therapeutic strategies for patients. Corneal alkali burn injury is a common type of ocular injury that is difficult to treat in the clinic. The cornea is a clear and avascular tissue. Corneal neovascularization after alkali burn injury is a serious complication; it not only seriously affects the patient's vision but also is the main reason for failed corneal transplantation. Corneal neovascularization affects approximately 1.4 million patients a year. We show for the first time that AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burns. The expression of AIP1 was decreased, while that of clv-IL-1ß and VEGFa was increased after alkali burns. We tried to elucidate the specific molecular mechanisms by which AIP1 regulates corneal neovascularization. NOX4 activation was due to decreased AIP1 expression in murine corneas with alkali burns. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. Additionally, NLRP3/NLRP6 expression was unbalanced, with NLRP3 activation and NLRP6 suppression in the corneal alkali burn murine model. Eye drops containing GLX351322, a NOX4 inhibitor, reversed the imbalance in NLRP3/NLRP6 by reducing ROS expression. This treatment also reduced the expression of clv-IL-1ß and VEGFa, reducing neovascularization. Therefore, we provide new gene therapeutic strategies for patients. With the development of neovascularization therapy, we believe that in addition to corneal transplantation, new drug or gene therapies can achieve better results. Video Abstract.