Anti-tumor therapy of glycyrrhetinic acid targeted liposome co-delivery of doxorubicin and berberine for hepatocellular carcinoma.

During the development of hepatocellular carcinoma (HCC), hepatic stellate cells undergo activation and transform into cancer-associated fibroblasts (CAFs) due to the influence of tumor cells. The interaction between CAFs and tumor cells can compromise the effectiveness of chemotherapy drugs and promote tumor proliferation, invasion, and metastasis. This study explores the potential of glycyrrhetinic acid (GA)-modified liposomes (lip-GA) as a strategy for co-delivery of berberine (Ber) and doxorubicin (Dox) to treat HCC. The characterizations of liposomes, including particle size, zeta potential, polydispersity index, stability and in vitro drug release, were investigated. The study evaluated the anti-proliferation and anti-migration effects of Dox&Ber@lip-GA on the Huh-7 + LX-2 cell model were through MTT and wound-healing assays. Additionally, the in vivo drug distribution and anti-tumor efficacy were investigated using the H22 + NIH-3T3-bearing mouse model. The results indicated that Dox&Ber@lip-GA exhibited a nanoscale particle size, accumulated specifically in the tumor region, and was efficiently taken up by tumor cells. Compared to other groups, Dox&Ber@lip-GA demonstrated higher cytotoxicity and lower migration rates. Additionally, it significantly reduced the deposition of extracellular matrix (ECM) and inhibited tumor angiogenesis, thereby suppressing tumor growth. In conclusion, Dox&Ber@lip-GA exhibited superior anti-tumor effects both in vitro and in vivo, highlighting its potential as an effective therapeutic strategy for combating HCC.

Neurotrophic Keratopathy in the United States: An Intelligent Research in Sight Registry Analysis.

PURPOSE: To describe the characteristics of neurotrophic keratopathy (NK) in the United States. DESIGN: Retrospective database study. PARTICIPANTS: Thirty-one thousand nine hundred fifteen eyes of 27 483 patients with a diagnosis of NK. METHODS: Retrospective analysis of visits associated with a diagnosis of NK between 2013 and 2018 using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. MAIN OUTCOME MEASURES: Demographic information, prevalence, visual acuity (VA), concomitant diagnosis and procedure codes, and risk factors impacting VA most closely after NK onset date. RESULTS: Mean ± standard deviation (SD) age at initial diagnosis of NK was 68.0 ± 16.0 years, and 58.91% of patients were women (P < 0.0001). Presentation was unilateral in 58.14%, bilateral in 16.13%, and unspecified in 25.73%. Average 6-year prevalence of NK in the IRIS Registry was 21.34 cases per 100 000 patients. Mean ± SD VA was 0.60 ± 0.79 logMAR before diagnosis and 0.88 ± 0.94 logMAR after diagnosis (P < 0.0001). Most common concomitant diagnoses included herpetic keratitis (33.70%), diabetes (31.59%), and corneal dystrophy (14.28%). Common procedures for NK management included the use of amniotic membrane (29.90%), punctal plugs (29.65%), and bandage contact lenses (22.67%). Age, male sex, Black race, Hispanic or Latino ethnicity, unilateral involvement, concomitant diagnoses of diabetes, corneal transplantation, and herpetic keratitis were associated significantly with worse VA. CONCLUSIONS: Based on the IRIS Registry, the prevalence of NK is 21.34 cases per 100 000 patients. Visual acuity was significantly worse after NK diagnosis compared with other time points. Neurotrophic keratopathy was associated most commonly with herpetic keratitis and diabetes. Worse VA in patients with NK was associated with several demographic characteristics, history of diabetes, corneal transplantation, and herpetic keratitis.

Practical Guidance for the Use of Loteprednol Etabonate Ophthalmic Suspension 0.25% in the Management of Dry Eye Disease.

Dry eye disease (DED) is a prevalent ocular surface disease. Like with any chronic disease, patients with DED can experience episodic flares. There are many existing and upcoming treatments for the chronic treatment of DED, yet treatments for DED flares are limited. Loteprednol etabonate 0.25% is an FDA approved treatment modality for the short-term treatment of the signs and symptoms of DED. This medication is formulated with the customized mucus-penetrating particle (MPP) technology, which has a greater ability to penetrate the ocular surface and more effectively deliver the active steroid to the ocular surface tissues as compared with conventional steroid preparations. There is also increasing utility of loteprednol etabonate 0.25% in the treatment of DED before and/or after cataract or refractive surgery or as induction therapy prior to starting chronic immunomodulatory medication for DED.

Punctal Congestion Syndrome: A Reversible, Functional Punctal Stenosis Causing Epiphora in the Setting of Chronic Pretarsal Conjunctivitis.

PURPOSE: To describe a reversible syndrome of epiphora, functional punctal stenosis, and chronic pretarsal conjunctivitis associated with corticosteroid or corticosteroid-antibiotic eyedrop use. METHODS: This is an Institutional Review Board-approved retrospective review of patients diagnosed with epiphora, punctal stenosis, and chronic conjunctivitis by a single surgeon (B.J.W.). These patients were subsequently invited to participate in a prospective study involving allergy skin patch testing for ophthalmic drops, common excipients, and active ingredients. RESULTS: Thirteen patients received a diagnosis of punctal congestion syndrome. The average age was 63 years (range, 41-93) and 69.2% were female. Findings were bilateral in 61.5%. All had used preserved drops in the affected eye(s). Various antecedent diagnoses resulted in treatment with preserved drops. Patients experienced epiphora for an average of 3.8 months (median, 3 months; mode, 3 months; range, 1-8 months) prior to presentation. Two patients had undergone punctoplasty which failed to resolve symptoms. 92.3% of patients had been taking tobramycin-dexamethasone drops, loteprednol drops, or a combination of both prior to presentation. All were taken off preserved drops. 69.2% were also treated with a preservative-free loteprednol etabonate 0.5% ophthalmic ointment taper. All improved. Partial relief of symptoms was achieved by an average of 1.6 months (median, 2 months; mode, 2 months; standard deviation, ±0.7 months) and resolution of symptoms by 2.5 months (median, 2 months; mode, 2 months; standard deviation, ±1.7 months). One patient underwent patch testing with strong positive reactions to formaldehyde and neomycin and a weak positive reaction to gentamicin. CONCLUSIONS: Functional punctal stenosis is associated with topical ophthalmic preparations, especially preserved corticosteroids and antibiotic-corticosteroid combinations. Treatment consists of removal of all preserved eyedrops. Symptoms often improve over several months.

Henoch-Schönlein Purpura Associated With Diffuse Large B-cell Lymphoma of the Orbit.

The association between Henoch-Schönlein purpura (HSP) and neoplasia is rare and has been more commonly reported in cases of solid tumors rather than hemotological malignancies. To the authors' knowledge, HSP in association with orbital lymphoma has not been previously reported. An 84-year-old man underwent anterior orbitotomy with biopsy for a rapidly growing orbital mass. Immediately following this procedure, he developed petechial rash, flash pulmonary edema, and kidney dysfunction with hematuria and proteinuria. Orbital biopsy revealed diffuse large B-cell lymphoma while skin and kidney biopsies showed features consistent with HSP. Multidisciplinary team involvement and treatment with chemotherapy and corticosteroid resulted in an excellent clinical response. Clinicians should be aware that HSP and orbital diffuse large B-cell lymphoma can co-occur, potentially leading to life-threatening rapid fluid shifts and metabolic derangements.

Prevalence and Risk Factors of Exposure Keratopathy Across Different Intensive Care Units.

PURPOSE: To determine the prevalence and risk factors of exposure keratopathy (EK) across different intensive care units (ICU) at Columbia University Medical Center, including the Pediatric ICU (PICU), Medical ICU (MICU), and Neurologic ICU (NICU). METHODS: In this prospective cohort study, 65 patients were examined daily during their admission in the PICU (27 patients), MICU (15 patients), and NICU (23 patients). Data on eyelid position, conjunctival and corneal changes, Bell's and blink reflexes, medications, Glasgow Coma Scale rating, and ventilation type were collected. RESULTS: Overall EK percentages were as follows: PICU 19%, MICU 60%, and NICU 48%. The prevalence of EK was lowest in the PICU (P = 0.013). Factors associated with EK were lagophthalmos (P < 0.001), an absent Bell's reflex (P = 0.003), an absent blink reflex (P < 0.001), conjunctival injection (P < 0.001), a low Glasgow Coma Scale score (P < 0.001), intubation (P < 0.001), surgery before examination (P < 0.001), dialysis (P = 0.002), and administration of opioid (P < 0.001), sedative (P < 0.001), and neuromuscular blocking medications (P = 0.006). CONCLUSIONS: This is the first study to examine the rates and risk factors of EK across different ICU settings. The prevalence of EK was lowest in the PICU, which may partly be explained by the increased number of PICU patients receiving noninvasive ventilation and the absence of conjunctival chemosis.

Natural history, clinical course and predictors of interval time from initial diagnosis to development of subsequent NSCLC brain metastases.

PURPOSE: Non-small cell lung cancer (NSCLC) brain metastases are associated with substantial morbidity and mortality. During recent years, accompanying dramatic improvements in systemic disease control, NSCLC brain metastases have emerged as an increasingly relevant clinical problem. However, optimal surveillance practices remain poorly defined. This purpose of this study was to further characterize the natural history, clinical course and risk factors associated with earlier development of subsequent NSCLC brain metastases to better inform clinical practice and help guide survivorship care. METHODS: We retrospectively reviewed all institutional NSCLC brain metastasis cases treated with radiotherapy between 1997 and 2015. Exclusion criteria included presence of brain metastases at initial NSCLC diagnosis and incomplete staging information. Interval time to brain metastases and subsequent survival were characterized using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: Among 105 patients within this cohort, median interval time to development of brain metastases was 16 months. Median interval times were 29, 19, 16 and 13 months for Stage I-IV patients, respectively (P = 0.016). Additional independent predictors for earlier development of NSCLC brain metastases included non-adenocarcinomatous histopathology (HR 3.036, P < 0.001), no prior surgical resection (HR 1.609, P = 0.036) and no prior systemic therapy (HR 3.560, P = 0.004). Median survival following intracranial progression was 16 months. Delayed development of brain metastases was associated with better prognosis (HR 0.970, P < 0.001) but not survival following intracranial disease onset. CONCLUSIONS: Collectively, our results provide valuable insights into the natural history of NSCLC brain metastases. NSCLC stage, histology, prior surgical resection and prior systemic therapy emerged as independent predictors for interval time to brain metastases.