Browsing by Author "Mellerio, Jemima"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa
    (2024) Tartaglia, Grace; Fuentes, María; Pate,Neil; Varughese, Abigail; Pyung, Lauren; Pyung, Israel; Alexander, Michael; Poojan, Shiv; Cao, Qingqing; Solomon, Brenda; Padron, Zachary; Dyer, Jonathan; Mellerio, Jemima; McGrath, John; Palisson, Francis; Salas, Julio; Han, Lin; South, Andrew
    Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.
  • Thumbnail Image
    Item
    Multidisciplinary care of epidermolysis bullosa during the COVID-19 pandemic-Consensus: Recommendations by an international panel of experts
    (2020) Murrell, Dedee F; Lucky, Anne W; Salas-Alanis, Julio C; Woodley, David T; Palisson, Francis; Natsuga, Ken; Nikolic, Milos; Ramirez-Quizon, Mae; Paller, Amy S; Lara-Corrales, Irene; Barzegar, Mohammadreza Amir; Sprecher, Eli; Has, Cristina; Laimer, Martin; Bruckner, Anna L; Bilgic, Asli; Nanda, Arti; Purvis, Diana; Hovnanian, Alain; Murat-Sušić, Slobodna; Bauer, Johannes; Kern, Johannes S; Bodemer, Christine; Martin, Linda K; Mellerio, Jemima; Kowaleski, Cezary; Robertson, Susan J; Bruckner-Tuderman, Leena; Pope, Elena; Marinkovich, M Peter; Tang, Jean Y; Su, John; Uitto, Jouni; Eichenfield, Lawrence F; Teng, Joyce; Aan Koh, Mark Jean; Lee, Sang Eun; Khuu, Phuong; Rishel, Heather I; Sommerlund, Mette; Wiss, Karen; Hsu, Chao-Kai; Chiu, Tor Wo; Martinez, Anna E
  • Thumbnail Image
    Item
    Outcomes and Predictors for Re-stenosis of Esophageal Stricture in Epidermolysis Bullosa: A Multicenter Cohort Study
    (2020-09) Pope, Elena; Mansour, Mark; Berseneva, María; Liy-Wong, Carmen; Salas, Julio; Fuentes, Ignacia; Yubero, Maria Joao; Palisson, Francis; Martinez, Anna; Mellerio, Jemima; Lara-Corrales, Irene; Yang, Anes; Murrell, Dedee; Torres-Pradilla, Mauricio; Lucky, Anne
    Background: Esophageal strictures are the common gastrointestinal complications in patients with epidermolysis bullosa (EB) requiring dilation. There is limited information on the best type of intervention, outcomes, and predictors for re-stenosis. Objectives: We aimed to investigate the frequency, clinical presentation of esophageal strictures in EB patients, and to ascertain the predictors of re-stenosis. Methods: We conducted a retrospective, multicenter cohort study involving 7 specialized, international EB centers on patients who were 0 to 50 years of age. Descriptive statistics and hazard risks for re-stenosis were calculated. Results: We identified 125 patients with 497 esophageal stricture episodes over a mean period of observation of 17 (standard deviation [SD]¼ 11.91) years. Dilations were attempted in 90.74% of episodes, using guided fluoroscopy 45.23%, retrograde endoscopy 33.04%, and antegrade endoscopy 19.07%. Successful dilation was accomplished in 99.33% of attempts. Patients experienced a median of 2 (interquartile range [IQR]: 1–7) stricture episodes with a median interval between dilations of 7 (IQR: 4–12) months. Predictors for re-stenosis included: number of strictures (2 vs 1 stricture:x2¼ 4.293,P¼ 0.038, hazard ratio [HR]¼ 1.294 (95% confidence interval [CI]: 1.014–1.652 and 3 vs 1 stricture:x2¼ 7.986, P¼ 0.005, HR¼ 1.785 [95% CI: 1.194, 2.667]) and a long (1 cm) segment stricture (x2¼ 4.599, P¼ 0.032, HR¼ 1.347 (95% CI: 1.026– 1.769). Complications were more common with the endoscopic approach (8/86, antegrade endoscopy; 2 /149, retrograde endoscopy vs 2/204, fluoroscopy; x2¼ 17.39, P-value <0.000). Conclusions: We found excellent dilation outcomes irrespective of the dilation procedure; however, with higher complications in the endoscopic approach. Long (>1 cm) segment involvement and multiple locations were predictive of stricture reoccurrence.

Implementado por OpenGeek Services