Article
Genetics & Heredity
Lisha Shen, Whenshuai Xu, Jinsong Gao, Jun Wang, Jiannan Huang, Yani Wang, Yudi He, Yanli Yang, Xinlun Tian, Kai-Feng Xu
Summary: Complications such as worsened dyspnea, pneumothorax, and renal angiomyolipoma bleeding were common in LAM patients during pregnancy, especially in those who had been treated with Sirolimus before. Patients with a history of Sirolimus treatment had a higher risk of spontaneous abortion. However, discontinuing Sirolimus before or during pregnancy did not lead to adverse neonatal outcomes for patients without spontaneous abortion.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Medicine, General & Internal
Jeong Suk Koh, Sina Oh, Chaeuk Chung
Summary: This article reports a rare case of a patient with systemic lupus erythematosus (SLE) coexisting with pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML). The patient underwent selective transcatheter embolization for AML and successfully recovered after treatment.
Article
Critical Care Medicine
Nishant Gupta, Bin Zhang, Yuan Zhou, Francis X. McCormack, Rebecca Ingledue, Nathan Robbins, Elizabeth J. Kopras, Susan McMahan, Abhishek Singla, Jeffrey Swigris, Adam G. Cole, Marina K. Holz
Summary: Is the addition of resveratrol safe and more efficacious than sirolimus alone in patients with lymphangioleiomyomatosis? The addition of resveratrol was found to be safe and well tolerated in patients with lymphangioleiomyomatosis taking sirolimus and was associated with modest improvement in health-related quality of life.
Article
Multidisciplinary Sciences
Min Qiu, Yan Tang, Jinjin Chen, Rachel Muriph, Zhongfeng Ye, Changfeng Huang, Jason Evans, Elizabeth P. Henske, Qiaobing Xu
Summary: The challenge of delivering mRNA to specific organs and cells in vivo is being addressed, with research showing that N-series LNPs can selectively deliver mRNA to the lungs while O-series LNPs tend to deliver mRNA to the liver. By analyzing the protein corona on targeted LNPs, unique plasma proteins were identified that contribute to their targetability. This research demonstrates the potential of LNPs as a promising therapeutic intervention for lung diseases like lymphangioleiomyomatosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Eva Revilla-Lopez, Cristina Berastegui, Alejandra Mendez, Berta Saez-Gimenez, Victoria Ruiz de Miguel, Manuel Lopez-Meseguer, Victor Monforte, Carlos Bravo, Miguel Angel Pujana, Maria Antonia Ramon, Susana Gomez-Olles, Antonio Roman
Summary: This study found that sirolimus treatment had a positive long-term effect on most LAM patients, with 59% showing a positive response, 30% showing a partial response, and 11% showing a negative response after 5 years of treatment.
SCIENTIFIC REPORTS
(2021)
Article
Respiratory System
Jesse D. Kirkpatrick, Ava P. Soleimany, Jaideep S. Dudani, Heng-Jia Liu, Hilaire C. Lam, Carmen Priolo, Elizabeth P. Henske, Sangeeta N. Bhatia
Summary: Activity-based nanosensors enable noninvasive, real-time monitoring of disease progression and treatment response in a preclinical model of LAM.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Medicine, General & Internal
Ergin Erginoz, Halit Eren Taskin, Gokce Hande Cavus, Abdullah Kagan Zengin
Summary: Tuberous sclerosis complex is a genetic disorder with manifestations in various organs due to mutations in tumor suppressor genes. Perivascular epithelioid cell tumors, including lymphangioleiomyomatosis, have been linked to these gene mutations. The study presented a case of a 28-year-old woman with multiple manifestations of tuberous sclerosis complex, who underwent surgical procedures for colonic tumor and subsequently developed SARS-CoV-2 infection.
Article
Medicine, General & Internal
David Paiva, Anabela De Carvalho, Ana Luisa Campos, Filipa Goncalves, Cristina Silva, Olinda Miranda, Sandra Barbosa, Jorge Cotter
Summary: Tuberous sclerosis is a rare genetic disease that can be associated with lymphangioleiomyomatosis, characterized by multiple skin lesions. It may lead to severe hyponatremia, requiring prompt treatment and diagnosis by a multidisciplinary team.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Medicine, General & Internal
Silvia Terraneo, Elena Lesma, Silvia Ancona, Gianluca Imeri, Giuseppina Palumbo, Olga Torre, Lisa Giuliani, Stefano Centanni, Angela Peron, Silvia Tresoldi, Paola Cetrangolo, Fabiano Di Marco
Summary: MMP-2 and MMP-7 levels were higher in LAM patients compared to healthy individuals and those with TSC. VEGF-D levels were higher in both S-LAM and TSC-LAM patients, but lower in TSC patients and controls. The study suggests that MMP-2 and MMP-7 could be potential biomarkers for LAM diagnosis.
FRONTIERS IN MEDICINE
(2021)
Article
Pathology
Chihiro Inoue, Ryoko Saito, Satsuki Kishikawa, Takuo Hayashi, Toshio Kumasaka, Takehiro Yamada, Hisashi Oishi, Yuto Yamazaki, Fumiyoshi Fujishima, Mika Watanabe, Hironobu Sasano
Summary: After performing genetic analysis on the lesions of a 30-something female who underwent lung transplantation, it was found that multifocal micronodular pneumocyte hyperplasia exhibited benign characteristics.
Article
Genetics & Heredity
Yang Zhao, Hao Guo, Wenda Wang, Guoyang Zheng, Zhan Wang, Xu Wang, Yushi Zhang
Summary: Our study identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs) in TSC-RAML, with 6 DECs further confirmed by q-PCR. A competitive endogenous RNA (ceRNA) regulatory network comprising 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was up-regulated, while humoral immune response and leukocyte chemotaxis pathway were down-regulated in TSC-RAML. The enrichment of fibroblasts in TSC-RAML and the correlation of up-regulated circRNA_000799 and circRNA_025332 with fibroblast infiltration were highlighted.
Article
Medicine, General & Internal
Bartlomiej Pawlik, Urszula Smyczynska, Szymon Grabia, Wojciech Fendler, Izabela Drozdz, Katarzyna Babol-Pokora, Katarzyna Kotulska, Sergiusz Jozwiak, Julita Borkowska, Wojciech Mlynarski, Joanna Trelinska
Summary: This study aimed to analyze the serum miRNA profiles in patients with tuberous sclerosis (TSC) treated with sirolimus, and compare them with those previously treated with everolimus. The results showed significant differences in miRNA expression before and after sirolimus treatment. Some miRNAs were dysregulated in the same directions compared with the everolimus group. Pathway analysis indicated the involvement of the Ras and MAPK signaling pathway. The upregulation of specific miRNAs was associated with the downregulation of the mTOR pathway.
JOURNAL OF CLINICAL MEDICINE
(2022)
Editorial Material
Medicine, General & Internal
Aiman Mushir, Sohail Akhtar, Mujahid Hussain
Summary: Lymphangioleiomyomatosis (LAM) is a multisystem disorder primarily affecting the lung, while Tuberous sclerosis complex (TSC) is characterized by multiple benign tumors in various organs. LAM can occur either sporadically or in association with TSC. There are several shared features between TSC and sporadic LAM. We present a case of TSC-LAM with pneumothorax and multiple manifestations.
JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
(2023)
Article
Medicine, General & Internal
Giorgia Sforza, Gabriele Monte, Alessandra Voci, Lorenzo Figa Talamanca, Laura Papetti, Michela Ada Noris Ferilli, Martina Proietti Checchi, Massimiliano Valeriani, Romina Moavero
Summary: This article presents a case study of a 10-year-old boy who was diagnosed with radiologically isolated syndrome (RIS) after being diagnosed with tuberous sclerosis complex (TSC). It is the third reported case of the co-occurrence of TSC and demyelinating disease, suggesting a potential link between the two conditions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Respiratory System
Vincent Cottin, Elodie Blanchard, Mallorie Kerjouan, Romain Lazor, Martine Reynaud-Gaubert, Camille Taille, Yurdagul Uzunhanj, Lidwine Wemeau, Claire Andrejak, Dany Baud, Philippe Bonniaud, Pierre-Yves Brillet, Alain Calender, Lara Chalabreysse, Isabelle Court-Fortune, Nicolas Pierre Desbaillets, Gilbert Ferretti, Anne Guillemot, Laurane Hardelin, Marianne Kambouchner, Violette Leclerc, Mathieu Lederlin, Marie-Claire Malinge, Alain Mancel, Sylvain Marchand-Adam, Jean-Michel Maury, Jean-Marc Naccache, Mouhamad Nasser, Hilario Nunes, Gaele Pagnoux, Gregoire Prevot, Christine Rousset-Jablonski, Olivier Rouviere, Salim Si-Mohamed, Renaud Touraine, Julie Traclet, Segolene Turquier, Stephane Vagnarelli, Kais Ahmad
Summary: This article presents the English-language version of the French National Diagnostic and Care Protocol for lymphangioleiomyomatosis, a rare lung disease. The protocol provides practical recommendations for diagnosing, managing, and following up with patients. The recommendations cover various aspects of the disease, including diagnosis criteria, management principles, and use of pharmaceutical specialties and treatments.
RESPIRATORY MEDICINE AND RESEARCH
(2023)
Editorial Material
Clinical Neurology
Lauren C. Ditta, Jie Zhang, Wafi Bibars, John Bissler
JOURNAL OF NEURO-OPHTHALMOLOGY
(2021)
Article
Clinical Neurology
Alexander L. Cohen, Brechtje P. F. Mulder, Anna K. Prohl, Louis Soussand, Peter Davis, Mallory R. Kroeck, Peter McManus, Ali Gholipour, Benoit Scherrer, E. Martina Bebin, Joyce Y. Wu, Hope Northrup, Darcy A. Krueger, Mustafa Sahin, Simon K. Warfield, Michael D. Fox, Jurriaan M. Peters
Summary: The study found that tuber locations associated with infantile spasms were heterogeneous, and connected to the globi pallidi and cerebellar vermis. The connectivity with globus pallidus was a stronger predictor of spasms compared to tuber burden, indicating its potential in identifying patients at risk of infantile spasms.
ANNALS OF NEUROLOGY
(2021)
Article
Respiratory System
Saisakul Chernbumroong, Janice Johnson, Nishant Gupta, Suzanne Miller, Francis X. McCormack, Jonathan M. Garibaldi, Simon R. Johnson
Summary: Machine learning was used to identify clinically relevant clusters associated with complications and outcomes in Lymphangioleiomyomatosis (LAM) patients, dividing them into two to three groups. Assigning individuals to these clusters could improve decision-making and prognostic information for patients.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Clinical Neurology
Kate Mowrey, Hope Northrup, Peyton Rougeau, S. Shahrukh Hashmi, Darcy A. Krueger, Daniel Ebrahimi-Fakhari, Alexander J. Towbin, Andrew T. Trout, Jamie K. Capal, David Neal Franz, David Rodriguez-Buritica
Summary: The study on nonfunctional PNETs in TSC patients found a higher frequency compared to the general population, and individuals on systemic mTOR inhibitors had lower rates of tumor growth.
FRONTIERS IN NEUROLOGY
(2021)
Review
Medicine, Research & Experimental
Prashant Kumar, Fahad Zadjali, Ying Yao, John J. Bissler
Summary: Tuberous sclerosis complex (TSC) is linked to TSC1 or TSC2 gene mutations, which lead to overactivation of the mTORC1 pathway, resulting in abnormal tissue development and proliferation in the kidney, including both solid tumors and cystic lesions. Recent research in TSC nephrology highlights the role of extracellular vesicles and the innate immune system in disease pathogenesis.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Physiology
Prashant Kumar, Fahad Zadjali, Ying Yao, Brian Siroky, Aristotelis Astrinidis, Kenneth W. Gross, John J. Bissler
Summary: This study found that extracellular vesicles (EVs) derived from cells with Tsc1 and Tsc2 gene mutations, while having similar physical characteristics, modulate signaling pathways differently, potentially leading to heterogeneity in TSC.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Clinical Neurology
Samuel Alperin, Darcy A. Krueger, David N. Franz, Karen D. Agricola, Gabrielle Stires, Paul S. Horn, Jamie K. Capal
Summary: This study identified seven distinct overall TAND symptom profiles in TSC patients, ranging from high to low symptom burden. Analyzing specific TAND subpopulations with shared profiles may lead to a better understanding of TAND biology and enable more targeted treatments.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2021)
Article
Genetics & Heredity
Petrus J. de Vries, Loren Leclezio, Sugnet Gardner-Lubbe, Darcy Krueger, Mustafa Sahin, Steven Sparagana, Liesbeth De Waele, Anna Jansen
Summary: This study identified seven natural TAND clusters in individuals with TSC, providing a basis for tailored approaches to identification and treatment of TAND. The clusters showed good clinical face validity and may have differential responses to treatments.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Clinical Neurology
S. Katie Z. Ihnen, Jamie K. Capal, Paul S. Horn, Molly Griffith, Mustafa Sahin, E. Martina Bebin, Joyce Y. Wu, Hope Northrup, Darcy A. Krueger
Summary: This study found that epilepsy in TSC patients is heterogeneous, with distinct subgroups having different epilepsy profiles. Subgroups with higher seizure burden had worse developmental outcomes at 36 months. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.
PEDIATRIC NEUROLOGY
(2021)
Article
Clinical Neurology
Hope Northrup, Mary E. Aronow, E. Martina Bebin, John Bissler, Thomas N. Darling, Petrus J. de Vries, Michael D. Frost, Zoe Fuchs, Elizabeth S. Gosnell, Nishant Gupta, Anna C. Jansen, Sergiusz Jozwiak, J. Chris Kingswood, Timothy K. Knilans, Francis X. McCormack, Ashley Pounders, Steven L. Roberds, David F. Rodriguez-Buritica, Jonathan Roth, Julian R. Sampson, Steven Sparagana, Elizabeth Anne Thiele, Howard L. Weiner, James W. Wheless, Alexander J. Towbin, Darcy A. Krueger
Summary: The diagnostic criteria and management recommendations for tuberous sclerosis complex (TSC) were revised in 2018 based on advancements in knowledge and new therapies since 2013. Changes were made mainly to clinical and genetic diagnostic criteria, as well as surveillance and management standards. These updates aim to provide an improved care framework for individuals with TSC and their families.
PEDIATRIC NEUROLOGY
(2021)
Article
Clinical Neurology
Daniel Ebrahimi-Fakhari, Gabrielle Stires, Eunice Hahn, Darcy Krueger, David Neal Franz
Summary: Maternal sirolimus appears to be a safe and effective treatment option for prenatally detected rhabdomyomas due to tuberous sclerosis complex. Different dosing regimens and trough levels were used, with gradual shrinkage of cardiac rhabdomyomas observed in all patients. Weekly follow-up visits with fetal ultrasound, echocardiography, and laboratory work are recommended during the treatment period.
PEDIATRIC NEUROLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Krishnan Warrior, Lorriana E. Leard, Arun R. Nair, Cynthia J. Gries, Andrew J. Fisher, Simon R. Johnson, Francis X. McCormack, Daniel F. Dilling
Summary: There is significant variability in the use of mTOR inhibitors in LAM patients on the lung transplant waiting list worldwide. Our survey suggests favorable outcomes for those patients who continue mTOR inhibitor use up to the time of transplant.
RESPIRATORY MEDICINE
(2022)
Article
Pediatrics
Thomas Boat, Elizabeth Hente, William Hardie, Rhonda Szczesniak, Emrah Gecili, Grace Zhou, Jacqueline Taylor, Raouf Amin
Summary: During pulmonary exacerbation in youth with cystic fibrosis, many patients have decreased muscle mass and disproportionate fat, regardless of BMI. Weight gain during hospital treatment primarily represents fat deposition, while muscle mass and strength do not improve. These observations suggest the need for trials of interventions aimed at increasing muscle mass and function, and limiting fat accumulation during pulmonary exacerbation.
PEDIATRIC PULMONOLOGY
(2023)
Article
Clinical Neurology
Alexander L. Cohen, Mallory R. Kroeck, Juliana Wall, Peter McManus, Arina Ovchinnikova, Mustafa Sahin, Darcy A. Krueger, E. Martina Bebin, Hope Northrup, Joyce Y. Wu, Simon K. Warfield, Jurriaan M. Peters, Michael D. Fox, Tuberous Sclerosis Complex Autism Center Of Excellence Network Study Group
Summary: This study found a significant association between tubers involving the right fusiform face area and ASD diagnosis in TSC, with a 3.7-fold increased risk. This highlights a potentially causative mechanism for developing autism in TSC, which may guide research into ASD symptoms more generally.
ANNALS OF NEUROLOGY
(2023)
Article
Respiratory System
Jack Reifenberg, Emrah Gecili, Teresa Pestian, Eleni-Rosalina Andrinopoulou, Patrick H. Ryan, Cole Brokamp, Joseph M. Collaco, Rhonda D. Szczesniak
Summary: This study estimated the association between secondhand smoke exposure and decline in lung function in children with cystic fibrosis (CF) through a systematic review. The results indicated that secondhand smoke exposure is significantly correlated with a decrease in FEV1. These findings have important implications for future environmental health interventions in pediatric CF care.
JOURNAL OF CYSTIC FIBROSIS
(2023)