Review
Ophthalmology
Vahid Mansouri
Summary: This article reviews the genetic pathology of X-linked retinitis pigmentosa (XLRP) and discusses the preclinical aspects of XLRP gene therapy, animal models, associated assessments, and future challenges and directions.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Genetics & Heredity
Samuel Koller, Tim Beltraminelli, Jordi Maggi, Agnes Wlodarczyk, Silke Feil, Luzy Baehr, Christina Gerth-Kahlert, Moreno Menghini, Wolfgang Berger
Summary: X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is one of the most severe forms of RP due to its early onset and intractable progression. Most cases have been associated with genetic variants within the purine-rich exon ORF15 region of this gene. RPGR retinal gene therapy is currently being investigated in several clinical trials. Therefore, it is crucial to report and functionally characterize (all novel) potentially pathogenic DNA sequence variants. Whole-exome sequencing (WES) was performed for the index patient. The splicing effects of a non-canonical splice variant were tested on cDNA from whole blood and a minigene assay. Transcript analyses with minigene assays and cDNA from peripheral blood are useful tools for the characterization of splicing defects due to variants in the RPGR and may increase the diagnostic yield in RP. The functional analysis of non-canonical splice variants is required to classify those variants as pathogenic according to the ACMG's criteria.
Article
Genetics & Heredity
Hong-Li Liu, Feng-Guan Gao, Dan-Dan Wang, Fang-Yuan Hu, Ping Xu, Qing Chang, Ge-Zhi Xu, Ji-Hong Wu
Summary: This study investigates the clinical and genetic characteristics of the RPGR gene in a Chinese cohort, expanding the known mutational spectrum and providing a new reference for genetic diagnosis of RPGR variants.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Friederike Kortum, Sinja Kieninger, Pascale Mazzola, Susanne Kohl, Bernd Wissinger, Holger Prokisch, Katarina Stingl, Nicole Weisschuh
Summary: Our study validated the impact of non-canonical splice site variants in the RPGR gene on patients with retinitis pigmentosa. Through in vitro splice analysis, we identified different aberrant splicing events, expanding the landscape of pathogenic variants in RPGR and improving genetic diagnostic rates, ultimately enabling patients carrying these variants to participate in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Danial Roshandel, Tina M. Lamey, Jason Charng, Rachael C. Heath Jeffery, Terri L. McLaren, Jennifer A. Thompson, John N. De Roach, Samuel McLenachan, David A. Mackey, Fred K. Chen
Summary: Microperimetry and adaptive optics imaging revealed early functional and structural changes in asymptomatic RPGR mutation carriers, suggesting the importance of considering these assessments in the clinical evaluation of these patients.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Ophthalmology
Anna Paola Salvetti, Anika Nanda, Robert E. MacLaren
Summary: This study described 3 cases of severely affected female patients with XLRP, presenting with a male phenotype. These patients started to experience night blindness at an early age, with disease characteristics similar to males. One patient underwent retina implant surgery due to severe retinal atrophy.
Review
Pharmacology & Pharmacy
Cristina Martinez-Fernandez de la Camara, Jasmina Cehajic-Kapetanovic, Robert E. MacLaren
Summary: This manuscript reviews the development of gene therapy products for X-linked retinitis pigmentosa caused by RPGR mutations, and discusses the challenges faced by scientists and clinicians. The incomplete understanding of the underlying genetics and mechanism of action of RPGR, as well as the instability of the RPGR gene, pose significant challenges in developing effective gene therapy products.
EXPERT OPINION ON EMERGING DRUGS
(2022)
Article
Ophthalmology
Marcella Nebbioso, Federica Franzone, Alessandro Lambiase, Maurizio La Cava, Fabiana Mallone, Antonio Pizzuti, Enrica Marchionni
Summary: This study reevaluated a previously reported family affected by Coats'-type RP without genetic diagnosis and found it to be the first reported family with a Coats'-type RP associated with a RPGR mutation. This confirms the genetic origin hypothesis of this condition and expands the phenotypic spectrum of diseases caused by RPGR gene mutations. The Authors suggest RPGR gene screening mutations in patients presenting this phenotype.
Article
Ophthalmology
Laura J. Wood, Jasleen K. Jolly, Amandeep S. Josan, Thomas M. W. Buckley, Robert E. MacLaren
Summary: In both Choroideremia and RPGR-associated RP, low luminance VA and subsequent low luminance deficit are useful markers of central macular visual function.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Review
Genetics & Heredity
Junxing Yang, Lin Zhou, Jiamin Ouyang, Xueshan Xiao, Wenmin Sun, Shiqiang Li, Qingjiong Zhang
Summary: The study revealed that most pathogenic variants of RPGR are truncations, with missense and in-frame variants mainly located in the RCC1-like domain. Significant differences were found in best corrected visual acuity (BCVA) and refractive error between male and female carriers. Age increase and ORF15 variants contribute to the reduction of BCVA in male patients.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Katarzyna Nowomiejska, Katarzyna Baltaziak, Paulina Calka, Marzanna Ciesielka, Grzegorz Teresinski, Robert Rejdak
Summary: The goal of this study was to explore the spectrum of pathogenic variants in the RPGR gene in male Polish patients with retinitis pigmentosa. The study found 2 pathogenic and 5 likely pathogenic variants in 8 patients (18%), with 5 of the variants being novel and 5 being identified in the ORF15 mutational hotspot of the RPGR gene. The majority of patients had visual field constriction and thinning of the central foveal thickness. Dizygotic twins with the same mutation showed different retinal phenotypes, indicating variations in symptom severity.
Review
Ophthalmology
Thomas M. W. Buckley, Jasleen K. Jolly, Amandeep Singh Josan, Laura J. Wood, Jasmina Cehajic-Kapetanovic, Robert E. MacLaren
Summary: Microperimetry is a precise technique used to assess central retinal function, and has played a critical role in RPGR-related RP gene therapy trials. This review summarizes the principles of microperimetry, specific parameters for outcome measures in clinical trials, and the current state of structure-function correlations in RPGR-related retinitis pigmentosa.
ACTA OPHTHALMOLOGICA
(2021)
Article
Ophthalmology
Fahimeh Beigi, Marta Del Pozo-Valero, Inmaculada Martin-Merida, Masoud Reza Manaviat, Carmen Ayuso, Nasrin Ghasemi
Summary: Mutations in the RPGR gene's ORF15 region can cause X-linked retinitis pigmentosa, with some mutations being undetectable by NGS. A study on an Iranian family showed that after inconclusive NGS results, Sanger sequencing revealed a mutation in the ORF15 region, which was found in affected homozygous females for the first time.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Christine Voessing, Paul Atigbire, Jannis Eilers, Fenja Markus, Knut Stieger, Fei Song, John Neidhardt
Summary: This study identifies distinct functional properties of major RPGR isoforms, despite their similar subcellular localization. A tissue-specific expression ratio between RPGR(skip14/15) and RPGR(ex1-19) seems required to regulate the ciliary concentration of RPGR interaction partners.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Moreno Menghini, Jasleen K. Jolly, Anika Nanda, Laura Wood, Jasmina Cehajic-Kapetanovic, Robert E. MacLaren
Summary: This study analyzed the foveal photoreceptor outer segment length in RPGR patients, finding early thinning in these patients, which might explain the lower visual acuity observed. These findings are important for assessing efficacy outcome measures in retinal gene therapy trials.
Article
Medicine, General & Internal
Johanna S. van Zyl, Amit Alam, Joost Felius, Ronnie M. Youssef, Dipesh Bhakta, Christina Jack, Aayla K. Jamil, Shelley A. Hall, Goran B. Klintmalm, Cedric W. Spak, Robert L. Gottlieb
Summary: This study analyzed albumin trends and lymphocyte percentage in COVID-19 patients to predict progression to critical disease, proposing a simple tool called ALLY to identify high-risk patients. The tool was validated in an independent group and showed promising results in identifying patients at risk of disease progression.
JOURNAL OF INVESTIGATIVE MEDICINE
(2021)
Article
Surgery
Johanna S. van Zyl, Teena Sam, Donna M. Clark, Joost Felius, Amanda K. Doss, Kacie R. Kerlee, Zi-On Cheung, Katalin Martits-Chalangari, Aayla K. Jamil, Sandra A. Carey, Robert L. Gottlieb, Cesar Y. Guerrero-Miranda, Parag Kale, Shelley A. Hall
Summary: LCPT demonstrated non-inferiority in efficacy compared to IR-tacrolimus in adult OHT recipients, with similar safety profile and improved bioavailability.
CLINICAL TRANSPLANTATION
(2021)
Article
Surgery
Aasim Afzal, Amit Alam, Johanna S. van Zyl, Hira Zafar, Joost Felius, Shelley A. Hall, Sandra A. Carey
Summary: This study retrospectively analyzed cardiac transplant recipients who experienced elevated dd-cfDNA without clinical rejection, identifying four distinct groups characterized by subclinical rejection with CMV infections, non-CMV infections with longer time to elevated dd-cfDNA, right ventricular dysfunction, and younger female patients with higher dd-cfDNA levels. Continued prospective analysis is needed to determine if these observations warrant changes in patient management for optimal utilization of this non-invasive graft surveillance tool.
CLINICAL TRANSPLANTATION
(2022)
Article
Surgery
Nishah Panchani, Philipp Schulz, Johanna Van Zyl, Joost Felius, Ronald Baxter, Eun Taek Yoon, Harith Baldawi, Amarinder Bindra, Sumeet K. Asrani
Summary: In patients with acute decompensated heart failure (ADHF), liver stiffness measurement (LSM) may serve as a novel noninvasive tool to determine left ventricular assist device (LVAD), heart transplant (HT), or death.
CLINICAL TRANSPLANTATION
(2022)
Article
Anesthesiology
Amit Alam, Aayla K. Jamil, Johanna S. Van Zyl, Horacio Medel-Martinez, Teodoro Bottiglieri, Brandi Wasek, Joost Felius, Brian Lima, Shelley A. Hall, Susan M. Joseph
Summary: This study investigated the efficacy of two biomarkers, TIMP-2 and IGFBP7, in predicting acute kidney injury (AKI) after left ventricular assist device (LVAD) implantation and cardiac transplantation. The results showed that assessing TIMP-2 and IGFBP7 within six hours after surgery appeared effective in predicting AKI in LVAD patients. Larger studies are needed to validate these findings.
JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
(2022)
Article
Medicine, General & Internal
R. L. Gottlieb, C. E. Vaca, R. Paredes, J. Mera, B. J. Webb, G. Perez, G. Oguchi, P. Ryan, B. U. Nielsen, M. Brown, A. Hidalgo, Y. Sachdeva, S. Mittal, O. Osiyemi, J. Skarbinski, K. Juneja, R. H. Hyland, A. Osinusi, S. Chen, G. Camus, M. Abdelghany, S. Davies, N. Behenna-Renton, F. Duff, F. M. Marty, M. J. Katz, A. A. Ginde, S. M. Brown, J. T. Schiffer, J. A. Hill
Summary: In symptomatic, nonhospitalized high-risk Covid-19 patients, a 3-day course of remdesivir significantly reduced the risk of hospitalization or death compared to placebo, with acceptable safety profile.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Aasim Afzal, Johanna van Zyl, Tariq Nisar, Aaron Y. Kluger, Aayla K. Jamil, Joost Felius, Shelley A. Hall, Parag Kale
Summary: This study investigated the trends in systolic and diastolic heart failure, finding an increase in admissions for diastolic heart failure. Overall, there was a decreasing trend in length of stay for heart failure, with a greater decrease observed in diastolic heart failure. Inpatient mortality decreased during the study period but stabilized in later years. Systolic heart failure was associated with higher mortality compared to diastolic heart failure. The study also found that the hospitalization costs for systolic heart failure were higher.
AMERICAN JOURNAL OF CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Gary Schwartz, Eleanor A. Huff, Johanna S. van Zyl, Briget da Graca, Gonzalo Gonzalez-Stawinski, Jorge Velazco, Timothy George, Michael J. Mack, Dan M. Meyer
Summary: This study evaluated the impact of coordinating and standardizing ECMO programs within a healthcare system. The results showed that the implementation of the ECMO collaborative project significantly improved patient survival rates, successful weaning from ECMO, and reduced complication rates.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Biochemistry & Molecular Biology
David Adams, Ivailo L. Tournev, Mark S. Taylor, Teresa Coelho, Violaine Plante-Bordeneuve, John L. Berk, Alejandra Gonzalez-Duarte, Julian D. Gillmore, Soon-Chai Low, Yoshiki Sekijima, Laura Obici, Chongshu Chen, Prajakta Badri, Seth M. Arum, John Vest, Michael Polydefkis
Summary: This study assessed the effectiveness of vutrisiran in patients with hereditary transthyretin amyloidosis. The results showed significant improvements in disease-relevant outcomes and an acceptable safety profile for vutrisiran.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Cardiac & Cardiovascular Systems
Hannah Copeland, Ivan Knezevic, David A. Baran, Vivek Rao, Michael Pham, Finn Gustafsson, Sean Pinney, Brian Lima, Marco Masetti, Agnieszka Ciarka, Navin Rajagopalan, Adriana Torres, Eileen Hsich, Jignesh K. Patel, Livia Adams Goldraich, Monica Colvin, Javier Segovia, Heather Ross, Mahazarin Ginwalla, Babak Sharif-Kashani, MaryJane A. Farr, Luciano Potena, Jon Kobashigawa, Maria G. Crespo-Leiro, Natasha Altman, Florian Wagner, Jennifer Cook, Valentina Stosor, Paolo A. Grossi, Kiran Khush, Tahir Yagdi, Susan Restaino, Steven Tsui, Daniel Absi, George Sokos, Andreas Zuckermann, Brian Wayda, Joost Felius, Shelley A. Hall
Summary: The proposed guidelines for donor heart selection are evidence-based and expert-consensus recommendations that were compiled by an international panel of experts after an extensive literature review.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Cardiac & Cardiovascular Systems
Aayla K. Jamil, Kristen M. Tecson, Tatyana T. Ganz, Shane Blankenship, Joost Felius, Sandra A. Carey, Shelley A. Hall
Summary: This study compared the experiences of heart transplant recipients undergoing non-invasive graft rejection testing with AlloMap(R) and invasive endomyocardial biopsy (EMB) surveillance. The results showed that patients had less pain and fewer adverse events with AlloMap(R) testing, and it could be performed at home, reducing the risk of infectious exposures.
Article
Cardiac & Cardiovascular Systems
Sandra A. Carey, Johanna S. van Zyl, Sarah Williams, Amit Alam, Neville Maliakkal, Hira I. Shakoor, Aayla K. Jamil, Joost Felius, Robin Germany, Aasim Afzal
Summary: Untreated sleep disorders pose risks of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, and home sleep apnea testing (HSAT) offers a potential solution.
AMERICAN JOURNAL OF CARDIOLOGY
(2023)
Article
Surgery
Amit Alam, Johanna S. van Zyl, Aasim Afzal, Joost Felius, Shelley A. Hall, Dan M. Meyer, Sandra A. Carey
Summary: Through evaluating the differences in dd-cfDNA between SCTS and traditional ice transportation, it was found that recipients in the SCTS group had a higher risk of elevated dd-cfDNA, indicating that graft injury may not have been completely eliminated. However, despite older donors and longer ischemic times in the SCTS group, no significant clinical differences were observed in short or long-term outcomes, including mortality, compared to the ice transportation group.
CLINICAL TRANSPLANTATION
(2023)
Article
Clinical Neurology
Laura Obici, Senda Ajroud-Driss, Kon-Ping Lin, John L. Berk, Julian D. Gillmore, Parag Kale, Haruki Koike, David Danese, Emre Aldinc, Chongshu Chen, John Vest, David Adams
Summary: The use of Vutrisiran as a treatment option for patients with ATTRv amyloidosis with polyneuropathy can significantly improve their quality of life and physical function. The treatment effect is most pronounced in patients who are diagnosed and treated early.
NEUROLOGY AND THERAPY
(2023)
Article
Ophthalmology
Thaddeus S. McClatchey, Scott R. Lambert, David G. Morrison, Stacey J. Kruger, Lorri B. Wilson, Scott K. McClatchey
Summary: This study compared the rate of refractive growth (RRG3) of the crystalline lens (lens) versus the eye excluding the lens (globe). The findings showed that the RRG3 of the globe was greater than that of the lens in normal eyes, and eyes with a faster rate of globe growth tended to have a faster rate of lens growth.
OPHTHALMOLOGY SCIENCE
(2022)