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Introduction: Dry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED. Methods: Participants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer's test) and ocular symptoms (Ocular Surface Disease Index [OSDI]). Results: The study met its primary endpoints: the LCD group demonstrated significantly better Schirmer's test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p<0.001 for both). Scores for total OSDI, and symptoms and vision domains, significantly improved by Day 14 for LCD versus placebo, (p<0.05 for all) and were maintained to Day 56 (p<0.001). In addition, the LCD group demonstrated significantly improved tear film break-up time (TBUT) and tear film osmolarity, versus placebo, by Day 56 (p<0.001), along with significant improvements in corneal and conjunctival staining (p<0.001 for both), and inflammation (matrix metalloproteinase-9; p<0.001 for each eye). Total Standard Patient Evaluation of Eye Dryness (SPEED) score, and scores for the frequency and severity domains, were significantly improved by Day 14 for LCD versus placebo (p<0.05 for all) and maintained to Day 56 (p<0.001). There was no difference between groups for artificial tear usage. The supplement was well-tolerated. Discussion: Once-daily LCD supplementation significantly improved tear production, stability and quality, reduced ocular surface damage and inflammation, and improved participants' symptoms. LCD supplementation could offer a useful adjunct to artificial tears for patients with DED (NCT05481450).
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(1) Background: Iron deficiency without anemia (IDWA) is a prevalent health concern in premenopausal women. Oral supplementation of iron may be a viable solution to improve blood-iron status in women; however, the effects of a high-dose iron-supplement regimen have been associated with gastrointestinal side effects. Therefore, the purpose of the present study was to evaluate the effectiveness of a low-dose liquid fermented iron-bisglycinate supplement (LIS) on improving blood-iron status in premenopausal women with IDWA without increasing constipation or gastrointestinal distress. (2) Methods: 85 premenopausal women with IDWA (ferritin < 70 ng/dL and hemoglobin > 11.0 g/dL) took a LIS (27 mg) or a placebo (PLA) for 8 weeks. Blood draws were taken at Wk0 and Wk8 of the study to measure serum-iron markers. In addition, surveys of gastrointestinal distress were administered at Wk0, Wk4, and Wk8 while the profile of mood states (POMS) was surveyed at Wk0 and Wk8. (3) Results: Compared to the placebo, the LIS was able to increase serum ferritin (p = 0.03), total serum iron (p = 0.03), and mean corpuscular volume (p = 0.02), while exhibiting no significant interaction in subjective gastrointestinal distress (p > 0.05). No significant effects were detected for POMS (p > 0.05). (4) Conclusions: Supplementing with LIS appears to improve blood-iron status without causing significant gastrointestinal distress in premenopausal women with IDWA.
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Anemia Ferropénica , Anemia , Dispepsia , Enfermedades Gastrointestinales , Deficiencias de Hierro , Humanos , Femenino , Valores de Referencia , Hierro , Ferritinas , Hemoglobinas/análisis , Anemia Ferropénica/tratamiento farmacológicoRESUMEN
A 55-year-old woman presented with a 3-month history of right groin swelling, discomfort and impaired mobility. On examination, a palpable mass was noted both to the right of midline in the lower abdomen and in the right groin. MRI of the pelvis showed two masses involving the anterior abdominal wall and right groin, as well as lymph node involvement. CT imaging revealed multiple bilateral pulmonary metastases. Pathology demonstrated a myxohayline stroma morphology. Tumour was also notable for NR4A3 gene region rearrangement and mutation in KIT exon 11 at position c.1669 T>G. Based on these findings, she was diagnosed with extraskeletal myxoid chondrosarcoma (EMC). The patient has been on imatinib, a tyrosine kinase inhibitor with activity against KIT, for 3 years with stable disease. Metastatic EMC is generally treated with surgical resection and perioperative radiation therapy with adjuvant chemotherapy and is associated with poor prognosis.
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Condrosarcoma , Receptores de Esteroides , Condrosarcoma/diagnóstico por imagen , Condrosarcoma/tratamiento farmacológico , Condrosarcoma/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Mesilato de Imatinib/uso terapéutico , Persona de Mediana Edad , Mutación , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/genéticaRESUMEN
Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2-4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45-0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32-0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.
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The use of selective BRAF inhibitors (BRAFi) has produced remarkable outcomes for patients with advanced cutaneous melanoma harboring a BRAFV600E mutation. Unfortunately, the majority of patients eventually develop drug-resistant disease. We employed a genetic screening approach to identify gain-of-function mechanisms of BRAFi resistance in two independent melanoma cell lines. Our screens identified both known and unappreciated drivers of BRAFi resistance, including multiple members of the DBL family. Mechanistic studies identified a DBL/RAC1/PAK signaling axis capable of driving resistance to both current and next-generation BRAFis. However, we show that the SRC inhibitor, saracatinib, can block the DBL-driven resistance. Our work highlights the utility of our straightforward genetic screening method in identifying new drug combinations to combat acquired BRAFi resistance. SIGNIFICANCE: A simple, rapid, and flexible genetic screening approach identifies genes that drive resistance to MAPK inhibitors when overexpressed in human melanoma cells.