Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
Article SELECTION from Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com for Training Small Language Models (SLMs) in Domain-aware Content of Medical, Pharmaceutical, Life Sciences and Healthcare by 15 Subjects Matter
Article selection: Aviva Lev-Ari, PhD, RN
#1 – February 20, 2016
Contributions to Personalized and Precision Medicine & Genomic Research
kprompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class V: 7,500 Biological Images in LPBI Group’s Digital Art Media Gallery, as Prior Art
Curator: Aviva Lev-Ari, PhD, RN
We had researched the topic of AI Initiatives in Big Pharma in the following article:
Authentic Relevance of LPBI Group’s Portfolio of IP as Proprietary Training Data Corpus for AI Initiatives at Big Pharma
We are publishing a Series of Five articles that demonstrate the Authentic Relevance of Five of the Ten Digital IP Asset Classes in LPBI Group’s Portfolio of IP for AI Initiatives at Big Pharma.
For the Ten IP Asset Classes in LPBI Group’s Portfolio, See
This Corpus comprises of Live Repository of Domain Knowledge Expert-Written Clinical Interpretationsof Scientific Findings codified in the following five Digital IP ASSETS CLASSES:
• IP Asset Class V: 7,500 Biological Images in our Digital Art Media Gallery, as prior art. The Media Gallery resides in WordPress.com Cloud of LPBI Group’s Web site
BECAUSE THE ABOVE ASSETS ARE DIGITAL ASSETS they are ready for use as Proprietary TRAINING DATA and INFERENCE for AI Foundation Models in HealthCare.
Expert‑curated healthcare corpus mapped to a living ontology, already packaged for immediate model ingestion and suitable for safe pre-training, evals, fine‑tuning and inference. If healthcare domain data is on your roadmap, this is a rare, defensible asset.
The article TITLE of each of the five Digital IP Asset Classes matched to AI Initiatives in Big Pharma, an article per IP Asset Class are:
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class I: PharmaceuticalIntelligence.com Journal, 2.5MM Views, 6,250 Scientific articles and Live Ontology
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class II: 48 e-Books: English Edition & Spanish Edition. 152,000 pages downloaded under pay-per-view
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class III: 100 e-Proceedings and 50 Tweet Collections of Top Biotech and Medical Global Conferences, 2013-2025
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class V: 7,500 Biological Images in LPBI Group’s Digital Art Media Gallery, as Prior Art
Digital IP Class V’s image gallery is a “treasure trove” ready for Big Pharma AI, establishing prior art while powering multimodal breakthroughs. Technical Implications: Enables visual-enhanced models for disease detection and R&D acceleration. Business Implications: Supports $500M investments with ethical, diverse data for partnerships; licensing potential for grants/webinars. Unique Insight: As embedded prior art, these visuals create a “moat” in multimodal AI—extending series from text to imagery for holistic Pharma companies inference. Promotional with links to gallery/IP portfolio. Caps the series by adding visual depth to textual assets.
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class X: +300 Audio Podcasts Library: Interviews with Scientific Leaders
In the series of five articles, as above, we are presenting the key AI Initiatives in Big Pharma as it was created by our prompt to @Grok on 11/18/2025:
Generative AI tools that save scientists up to 16,000 hours annually in literature searches and data analysis.
Drug Discovery and Development Acceleration Pfizer uses AI, supercomputing, and ML to streamline R&D timelines
Clinical Trials and Regulatory Efficiency AI:
-Predictive Regulatory Tools
-Decentralize Trials
-inventory management
Disease Detection and Diagnostics:
– ATTR-CM Initiative
– Rare diseases
Generative AI and Operational Tools:
– Charlie Platform
– Scientific Data Cloud AWS powered ML on centralized data
– Amazon’s SageMaker /Bedrock for Manufacturing efficiency
– Global Health Grants:
Pfizer Foundation’s AI Learning Lab for equitable access to care and tools for community care
Partnerships and Education
– Collaborations: IMI Big Picture for 3M – sample disease database
– AI in Pharma AIPM Symposium: Drug discovery and Precision Medicine
– Webinars of AI for biomedical data integration
– Webinar on AI in Manufacturing
Strategic Focus:
– $500M R&D reinvestment by 2026 targets AI for Productivity
– Part of $7.7B cost savings
– Ethical AI, diverse DBs
– Global biotech advances: China’s AI in CRISPR
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class V: 7,500 Biological Images in LPBI Group’s Digital Art Media Gallery, as Prior Art
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class V: 7,500 Biological Images in LPBI Group’s Digital Art Media Gallery, as Prior Art
Overview: Fifth in LPBI Group’s five-article series on AI-ready digital IP assets for pharma. This piece spotlights IP Asset Class V—7,500 expert-selected biological images in the Digital Art Media Gallery—as proprietary training data and “prior art” for multimodal AI foundation models in healthcare. Leveraging a November 18, 2025, Grok prompt on Pfizer’s AI efforts, it maps the gallery to pharma applications, emphasizing visual data’s role in enhancing generative AI for diagnostics, drug discovery, and article drafting. Unlike text-heavy prior classes, this focuses on image-caption pairs for ingestion into platforms like Charlie, positioning them as a “treasure trove” for ethical, diverse AI training.Main Thesis and Key Arguments
Core Idea: LPBI’s 7,500 biological images (with captions) serve as defensible, expert-curated prior art and training data for Big Pharma AI, enabling multimodal inference that combines visuals with clinical insights—outpacing generic datasets by injecting human-selected domain knowledge.
Value Proposition: The ~8,000-image gallery (actual 7,500 noted) is a ready-to-ingest visual corpus for platforms like Pfizer’s Charlie, generating medical drafts and accelerating R&D. Valued within the series’ $50MM-equivalent portfolio; unique as embedded prior art in original texts, supporting ethical AI with diverse, ontology-mapped visuals.
Broader Context: Part of ten IP classes, with five (I-V, X) AI-primed; complements text assets (e.g., 6,250 articles, 48 e-books) by adding multimodal depth. Highlights live ontology for semantic integration, contrasting open-source data with proprietary, safe-for-healthcare inputs.
AI Initiatives in Big Pharma (Focus on Pfizer)Reuses the Grok prompt highlights, presented in a verbatim table:
Initiative Category
Description
Generative AI Tools
Generative AI tools that save scientists up to 16,000 hours annually in literature searches and data analysis.
Drug Discovery Acceleration
Drug Discovery and Development Acceleration Pfizer uses AI, supercomputing, and ML to streamline R&D timelines.
Disease Detection and Diagnostics: – ATTR-CM Initiative – Rare diseases.
Generative AI & Operational Tools
Generative AI and Operational Tools: – Charlie Platform – Scientific Data Cloud AWS powered ML on centralized data – Amazon’s SageMaker /Bedrock for Manufacturing efficiency – Global Health Grants: Pfizer Foundation’s AI Learning Lab for equitable access to care and tools for community care.
Partnerships & Education
Partnerships and Education – Collaborations: IMI Big Picture for 3M – sample disease database – AI in Pharma AIPM Symposium: Drug discovery and Precision Medicine – Webinars of AI for biomedical data integration – Webinar on AI in Manufacturing.
Strategic Focus
Strategic Focus: – $500M R&D reinvestment by 2026 targets AI for Productivity – Part of $7.7B cost savings – Ethical AI, diverse DBs – Global biotech advances: China’s AI in CRISPR.
Mapping to LPBI’s Proprietary DataCore alignment table (verbatim extraction, linking Pfizer initiatives to Class V assets):
AI Initiative at Big Pharma i.e., Pfizer
Biological Images selected by Experts embedded in original Text (Prior Art)
Generative AI Tools (16,000 hours saved)
(No specific mapping provided.)
Drug Discovery Acceleration
Gallery of ~8,000 Biological images and captions is a Treasure TROVE.
Gallery of ~8,000 Biological images and captions is a Treasure TROVE.
Generative AI & Operational Tools (Charlie, AWS, etc.)
Ingest into Charlie Platform the Media Gallery for generation of Medical article drafts.
Partnerships & Education (IMI, AIPM, webinars)
(No specific mapping provided.)
Strategic Focus ($500M reinvestment, ethics)
(No specific mapping provided.)
Methodologies and Frameworks
AI Training Pipeline: Ingest image-caption pairs into Charlie/AWS platforms for pre-training (multimodal foundation models), fine-tuning (e.g., diagnostics visuals), and inference (e.g., draft generation). Use living ontology for semantic tagging; prior art embedding ensures IP defensibility.
Productivity Model: Amplifies Pfizer’s 16,000-hour savings and $7.7B efficiencies by fueling generative tools with expert visuals; ethical emphasis on diverse DBs for global equity (e.g., AI Learning Lab).
Insights: References Grok prompt as real-time sourcing; quotes series-wide vision of assets as “codified digital treasures” for safe healthcare AI. Predicts revolution in visual inference for rare diseases/ATTR-CM.
Conclusions and Implications
Digital IP Class V’s image gallery is a “treasure trove” ready for Big Pharma AI, establishing prior art while powering multimodal breakthroughs. Technical Implications: Enables visual-enhanced models for disease detection and R&D acceleration. Business Implications: Supports $500M investments with ethical, diverse data for partnerships; licensing potential for grants/webinars. Unique Insight: As embedded prior art, these visuals create a “moat” in multimodal AI—extending series from text to imagery for holistic Pharma companies inference. Promotional with links to gallery/IP portfolio. Caps the series by adding visual depth to textual assets.
If you’d like cross-series analysis, image examples, or multimodal AI trends, let me know!
Paul G. Yock, Recipient of the 2024 National Medal of Technology and Innovation, Professor of Cardiovascular Medicine at Stanford Medical School
Curator: Aviva Lev-Ari, PhD, RN
NMTI Citation
Paul G. Yock, Stanford University
For innovations in interventional cardiology. Paul Yock’s visionary work understanding the human heart is applied around the world today to improve patient care and save countless lives. His creation of the Biodesign approach to training future leaders of biotechnology and health care ensures his insights and experience will benefit generations to come.
Recipients of the 2024 National Medal of Technology and Innovation, administered by President Joe Biden and Laureates of the National Medal of Science, administered by NSF
Paul Yock – The Martha Meier Weiland Professor in the School of Medicine and Professor of Bioengineering, Cardiovascular Medicine, and (by courtesy) of Mechanical Engineering
Scientific Leadership Council Member, Clark Center Faculty
Dr. Paul Yock is the Martha Meier Weiland Professor of Medicine and founding co-chair of Stanford’s Department of Bioengineering, with courtesy appointments in the Graduate School of Business and the Department of Mechanical Engineering. He is also founder and director of the Stanford Byers Center for Biodesign.
After completing his undergraduate and graduate studies at Amherst College and Oxford, respectively, Paul received his MD from Harvard Medical School followed by internship and residency training at the University of California, San Francisco and a fellowship in cardiology at Stanford. He began his faculty career as an interventional cardiologist at UCSF and then moved to Stanford in 1994.
Paul has authored over 300 peer-reviewed publications, chapters and editorials, two textbooks, and over 50 US patents. He is internationally known for his work in inventing, developing, and testing new devices, including the Rapid Exchange™ stenting and balloon angioplasty system, which is now the primary system in use worldwide. He also invented the fundamental approach to intravascular ultrasound imaging and founded Cardiovascular Imaging Systems (CVIS), later acquired by Boston Scientific. Recent awards include the Transcatheter Therapeutics (TCT) Career Achievement Award, the American College of Cardiology Distinguished Scientist Award, and the National Academy of Engineering’s 2018 Bernard M. Gordon Prize for Innovation in Engineering and Technology Education.
Bio
Yock began his faculty career as an interventional cardiologist at UC San Francisco and then moved to Stanford in 1994. Yock is known for his work in inventing, developing and testing new devices, including the
Rapid Exchange angioplasty and stenting system, which is the primary approach used worldwide. Yock also authored the fundamental patents for
intravascular ultrasound imaging, conducted the initial clinical trials and
established the Stanford Center for Research in Cardiovascular Interventions as a core laboratory for analysis of intravascular ultrasound clinical studies. He also
invented the Smart Needle and
is a co-inventor of the strain-reduction patch for wound healing.
Yock was founding Co-Chair of the Department of Bioengineering and continues research related to new device technologies.
Yock also was the founding director of the Stanford Byers Center for Biodesign – dedicated to advanced training in medical technology innovation.
Abstract: A catheter is provided for insertion in the he blood vessel of a patient for ultrasonically imaging the vessel wall. The catheter includes a tubular element and an internally housed drive cable for effective circumferential scan about the catheter of an ultrasonic generating means. Both the tubular element and the drive cable are of a size and flexibility sufficient to permit their introduction into the vessel and subsequent advancement through the vessel to the location of the vessel wall where imaging is desired.
Abstract: Devices and methods for obtaining a three-dimensional image of an internal body site are provided. The subject devices are elongated structures (e.g., catheters) having a plurality of ultrasonic transducers located at their distal end. The configuration of the plurality of ultrasonic transducers may be reversibly changed from a first to a second configuration, where the radial aperture of the plurality of ultrasonic transducers is greater in the second configuration than in the first configuration. A feature of certain embodiments of the subject invention is that the plurality of ultrasonic tranducers are configured in the second configuration as a substantially continuous set of transducers. In using the subject imaging devices, the distal end of the devices is positioned at the internal body site of interest while the plurality of ultrasonic transducers is in the first configuration.
Type: Application
Filed: November 10, 2004
Publication date: September 29, 2005
Inventors: Richard Popp, Ali Hassan, Christian Eversull, Jeremy Johnson, Paul Yock
Abstract: Apparatus for introduction into the vessel of a patient comprising a guiding catheter adapted to be inserted into the vessel of the patient and a device adapted to be inserted into the guiding catheter. The device includes a flexible elongate member and a sleeve carried by the flexible elongate member near the distal extremity thereof and extending from a region near the distal extremity to a region spaced from the distal extremity of the flexible elongate element. The device also includes a guide wire adapted to extend through the sleeve so that the guide wire extends rearwardly of the sleeve extending alongside of and exteriorally of the flexible elongate element into a region near the proximal extremity of the flexible elongate element.
Abstract: A catheter system for localized or semi-localized administration of agents through the wall of a blood vessel is provided. Various catheter system constructions which use at least one expandable occluding device to create an isolated region are provided. Constructions using one catheter and one occlusion device are provided, along with constructions using two catheters and multiple occlusion devices. The catheter system may include a catheter with a variable stiffness along its length. The catheter system may also include a guide wire integrated with an inner catheter. The catheter can infuse the agent into the blood vessel in a pressure regulated manner. Methods for delivery and infusion of the agent within a blood vessel are also provided.
Type: Application
Filed: February 20, 2004
Publication date: March 17, 2005
Inventors: Michi Garrison, Todd Brinton, Peter Campbell, Steve Roe, Stephen Salmon, Paul Yock
Abstract: Apparatus and method are described for introducing an imaging catheter to the coronary vasculature. A guiding catheter is introduced so that the distal end of the guiding catheter engages a coronary os. The distal end of the guiding catheter is shaped so that a mark on the distal end is oriented in a predetermined orientation relative to the coronary vasculature. An imaging catheter is then introduced through the guiding catheter and an image of the mark is produced with the imaging catheter while in the guiding catheter. In this manner, the relative orientation of the produced image and the coronary vasculature is known.
Type: Grant
Filed: October 20, 1997
Date of Patent: March 9, 1999
Assignee: Cardiovascular Imaging Systems, Inc.
Inventors: Paul Yock, Yue-Teh Jang, Stephen M. Salmon
Abstract: Apparatus and method are described for introducing an imaging catheter to the coronary vasculature. A guiding catheter is introduced so that the distal end of the guiding catheter engages a coronary os. The distal end of the guiding catheter is shaped so that a mark on the distal end is oriented in a predetermined orientation relative to the coronary vasculature. An imaging catheter is then introduced through the guiding catheter and an image of the mark is produced with the imaging catheter while in the guiding catheter. In this manner, the relative orientation of the produced image and the coronary vasculature is known.
Type: Grant
Filed: September 4, 1996
Date of Patent: March 10, 1998
Assignee: Cardiovascular Imaging Systems Inc.
Inventors: Paul Yock, Yue-Teh Jang, Stephen M. Salmon
Abstract: Apparatus and method are described for introducing an imaging catheter to the coronary vasculature. A guiding catheter is introduced so that the distal end of the guiding catheter engages a coronary os. The distal end of the guiding catheter is shaped so that a mark on the distal end is oriented in a predetermined orientation relative to the coronary vasculature. An imaging catheter is then introduced through the guiding catheter and an image of the mark is produced with the imaging catheter while in the guiding catheter. In this manner, the relative orientation of the produced image and the coronary vasculature is known.
Type: Grant
Filed: June 6, 1995
Date of Patent: January 28, 1997
Inventors: Paul Yock, Yue-Teh Jang, Stephen M. Salmon
“This milestone makes AISAP the first company in the world to secure FDA clearance in the CADx pathway for the comprehensive diagnosis of structural heart diseases using POCUS,”
Cardio is a cloud-based platform that includes four modules for the computer-assist diagnosis (CADx) of valvular pathologies and eight key cardiac measurements. Its advanced AI algorithms can evaluate a patient’s left ventricle ejection fraction, right and left ventricular dimensions, right ventricular fractional area change, atrial areas, ascending aorta diameter and inferior vena cava diameter in addition to identifying aortic stenosis or mitral, tricuspid or aortic regurgitation.
The platform, trained on more than 24 million echocardiography clips, was designed to help even inexperienced users scan and diagnose a majority of common heart issues within minutes without leaving the patient’s side. In addition, it can communicate with equipment manufactured by a variety of vendors, directing data to a physician’s electronic health record or PACS system as needed.
Ehud Raanani, MD, co-founder of AISAP and director of the Leviev Cardiovascular and Thoracic Center at Sheba Medical Center, said in a statement. “It marks a big step in our goal of delivering point-of-care assisted diagnosis, or POCAD, with unparalleled scalability and accessibility—from the largest academic centers to the most remote rural locations.”
Smadar Kort, MD, system director of noninvasive cardiac imaging at Stony Brook Medicine, who has experience with the platform
said:
“We know that structural heart disease and heart failure are the leading causes of hospitalization and morbidity in the U.S. Enabling a wide variety of qualified physicians to quickly and accurately diagnose these conditions at the bedside could lead to earlier detection and treatment, and better patient outcomes, as well as greater efficiencies and cost savings to health systems, while ultimately saving countless lives.”
Application of Natural Language Processing (NLP) on ~1MM cases of semi-structured echocardiogram reports: Identification of aortic stenosis (AS) cases – Accuracy comparison to administrative diagnosis codes (IDC 9/10 codes)
Reporter and Curator: Aviva Lev-Ari, PhD, RN
Large-Scale Identification of Aortic Stenosis and its Severity Using Natural Language Processing on Electronic Health Records
Background Systematic case identification is critical to improving population health, but widely used diagnosis code-based approaches for conditions like valvular heart disease are inaccurate and lack specificity. Objective To develop and validate natural language processing (NLP) algorithms to identify aortic stenosis (AS) cases and associated parameters from semi-structured echocardiogram reports and compare its accuracy to administrative diagnosis codes. Methods Using 1,003 physician-adjudicated echocardiogram reports from Kaiser Permanente Northern California, a large, integrated healthcare system (>4.5 million members), NLP algorithms were developed and validated to achieve positive and negative predictive values >95% for identifying AS and associated echocardiographic parameters. Final NLP algorithms were applied to all adult echocardiography reports performed between 2008-2018, and compared to ICD-9/10 diagnosis code-based definitions for AS found from 14 days before to six months after the procedure date. Results A total of 927,884 eligible echocardiograms were identified during the study period among 519,967 patients. Application of the final NLP algorithm classified 104,090 (11.2%) echocardiograms with any AS (mean age 75.2 years, 52% women), with only 67,297 (64.6%) having a diagnosis code for AS between 14 days before and up to six months after the associated echocardiogram. Among those without associated diagnosis codes, 19% of patients had hemodynamically significant AS (i.e., greater than mild disease). Conclusion A validated NLP algorithm applied to a systemwide echocardiography database was substantially more accurate than diagnosis codes for identifying AS. Leveraging machine learning-based approaches on unstructured EHR data can facilitate more effective individual and population management than using administrative data alone.
Large-scale identification of aortic stenosis and its severity using natural language processing on electronic health records
Systematic case identification is critical to improving population health, but widely used diagnosis code–based approaches for conditions like valvular heart disease are inaccurate and lack specificity.
Objective
To develop and validate natural language processing (NLP) algorithms to identify aortic stenosis (AS) cases and associated parameters from semi-structured echocardiogram reports and compare their accuracy to administrative diagnosis codes.
Methods
Using 1003 physician-adjudicated echocardiogram reports from Kaiser Permanente Northern California, a large, integrated healthcare system (>4.5 million members), NLP algorithms were developed and validated to achieve positive and negative predictive values > 95% for identifying AS and associated echocardiographic parameters. Final NLP algorithms were applied to all adult echocardiography reports performed between 2008 and 2018 and compared to ICD-9/10 diagnosis code–based definitions for AS found from 14 days before to 6 months after the procedure date.
Results
A total of 927,884 eligible echocardiograms were identified during the study period among 519,967 patients. Application of the final NLP algorithm classified 104,090 (11.2%) echocardiograms with any AS (mean age 75.2 years, 52% women), with only 67,297 (64.6%) having a diagnosis code for AS between 14 days before and up to 6 months after the associated echocardiogram. Among those without associated diagnosis codes, 19% of patients had hemodynamically significant AS (ie, greater than mild disease).
Conclusion
A validated NLP algorithm applied to a systemwide echocardiography database was substantially more accurate than diagnosis codes for identifying AS. Leveraging machine learning–based approaches on unstructured electronic health record data can facilitate more effective individual and population management than using administrative data alone.
Keywords
Aortic stenosis Echocardiography Machine learning Population health Quality and outcomes Valvular heart disease
Two brothers with MEPAN Syndrome: A Rare Genetic Disorder
Reporter: Amandeep Kaur
In the early 40s, a married couple named Danny and Nikki, had normal pregnancy and delivered their first child in October 2011. The couple was elated after the birth of Carson because they were uncertain about even conceiving a baby. Soon after birth, the parents started facing difficulty in feeding the newborn and had some wakeful nights, which they used to called “witching hours”. For initial six months, they were clueless that something was not correct with their infant. Shortly, they found issues in moving ability, sitting, and crawling with Carson. Their next half year went in visiting several behavioral specialists and pediatricians with no conclusion other than a suggestion that there is nothing to panic as children grow at different rates.
Later in early 2013, Caron was detected with cerebral palsy in a local regional center. The diagnosis was based on his disability to talk and delay in motor development. At the same time, Carson had his first MRI which showed no negative results. The parents convinced themselves that their child condition would be solved by therapies and thus started physical and occupational therapies. After two years, the couple gave birth to another boy child named Chase in 2013. Initially, there was nothing wrong with Chase as well. But after nine months, Chase was found to possess the same symptoms of delaying in motor development as his elder brother. It was expected that Chase may also be suffering from cerebral palsy. For around one year both boys went through enormous diagnostic tests starting from karyotyping, metabolic screen tests to diagnostic tests for Fragile X syndrome, lysosomal storage disorders, Friedreich ataxia and spinocerebellar ataxia. Gene panel tests for mitochondrial DNA and Oxidative phosphorylation (OXPHOS) deficiencies were also performed. No conclusion was drawn because each diagnostic test showed the negative results.
Over the years, the condition of boys was deteriorating as their movements became stiffer and ataxic, they were not able to crawl anymore. By the end of 2015, the boys had an MRI which showed some symmetric anomalies in their basal ganglia indicating a metabolic condition. The symptoms of Carson and Chase was not even explained by whole exome sequencing due to the absence of any positive result. The grievous journey of visits to neurologist, diagnostic tests and inconclusive results led the parents to rethink about anything happened erroneous due to them such as due to their lifestyle, insufficient intake of vitamins during pregnancy or exposure to toxic agents which left their sons in that situation.
During the diagnostic odyssey, Danny spent many restless and sleepless nights in searching PubMed for any recent cases with symptoms similar to his sons and eventually came across the NIH’s Undiagnosed Diseases Network (UDN), which gave a light of hope to the demoralized family. As soon as Danny discovered about the NIH’s Diseases Network, he gathered all the medical documents of both his sons and submitted the application. The submitted application in late 2015 got accepted a year later in December 2016 and they got their first appointment in early 2017 at the UDN site at Stanford. At Stanford, the boys had gone through whole-genome sequencing and some series of examinations which came back with inconclusive results. Finally, in February 2018, the family received some conclusive results which explained that the two boys suffer from MEPAN syndrome with pathogenic mutations in MECR gene.
MEPAN means Mitochondrial Enoyl CoA reductase Protein-Associated Neurodegeneration
MEPAN syndrome is a rare genetic neurological disorder
MEPAN syndrome is associated with symptoms of ataxia, optic atrophy and dystonia
The wild-type MECR gene encodes a mitochondrial protein which is involved in metabolic processes
The prevalence rate of MEPAN syndrome is 1 in 1 million
Currently, there are 17 patients of MEPAN syndrome worldwide
The symptoms of Carson and Chase of an early onset of motor development with no appropriate biomarkers and T-2 hyperintensity in the basal ganglia were matching with the seven known MEPAN patient at that time. The agonizing journey of five years concluded with diagnosis of rare genetic disorder.
Despite the advances in genetic testing and their low-cost, there are many families which still suffer and left undiagnostic for long years. To shorten the diagnostic journey of undiagnosed patients, the whole-exome and whole-genome sequencing can be used as a primary tool. There is need of more research to find appropriate treatments of genetic disorders and therapies to reduce the suffering of the patients and families. It is necessary to fill the gap between the researchers and clinicians to stimulate the development in diagnosis, treatment and drug development for rare genetic disorders.
The family started a foundation named “MEPAN Foundation” (https://www.mepan. org) to reach out to the world to educate people about the mutation in MECR gene. By creating awareness among the communities, clinicians, and researchers worldwide, the patients having rare genetic disorder can come closer and share their information to improve their condition and quality of life.
Happy 80th Birthday: Radioiodine (RAI) Theranostics: Collaboration between Physics and Medicine, the Utilization of Radionuclides to Diagnose and Treat: Radiation Dosimetry by Discoverer Dr. Saul Hertz, the early history of RAI in diagnosing and treating Thyroid diseases and Theranostics
Both authors contributed to the development, drafting and final editing of this manuscript and are responsible for its content.
Abstract
March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.
Dr. Saul Hertz was Director of The Massachusetts General Hospital’s Thyroid Unit, when he heard about the development of artificial radioactivity. He conceived and brought from bench to bedside the successful use of radioiodine (RAI) to diagnose and treat thyroid diseases. Thus was born the science of theragnostics used today for neuroendocrine tumors and prostate cancer. Dr. Hertz’s work set the foundation of targeted precision medicine.
Keywords: Dr. Saul Hertz, nuclear medicine, radioiodine
How to cite this article:
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med 2019;18:8-12
How to cite this URL:
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med [serial online] 2019 [cited 2021 Mar 2];18:8-12. Available from: http://www.wjnm.org/text.asp?2019/18/1/8/250309
Dr Saul Hertz (1905-1950) discovers the medical uses of radioiodine
Barbara Hertz, Pushan Bharadwaj, Bennett Greenspan»
Thyroid practitioners and patients are acutely aware of the enormous benefit nuclear medicine has made to mankind. This month we celebrate the 80th anniversary of the early use of radioiodine(RAI).
Dr. Saul Hertz predicted that radionuclides “…would hold the key to the larger problem of cancer in general,” and may just be the best hope for diagnosing and treating cancer successfully. Yes, RAI has been used for decades to diagnose and treat disease. Today’s “theranostics,” a term that is a combination of “therapy” and “diagnosis” is utilized in the treatment of thyroid disease and cancer.
This short note is to celebrate Dr. Saul Hertz who conceived and brought from bench to bedside the medical uses of RAI; then in the form of 25 minute iodine-128.
On March 31st 1941, Massachusetts General Hospital’s Dr. Saul Hertz (1905-1950) administered the first therapeutic use of Massachusetts Institute of Technology (MIT) cyclotron produced RAI. This landmark case was the first in Hertz’s clinical studies conducted with MIT, physicist Arthur Roberts, Ph.D.
[Photo – Courtesy of Dr Saul Hertz Archives ]
Dr Saul Hertz demonstrating RAI Uptake Testing
Dr. Hertz’s research and successful utilization of radionuclides to diagnose and treat diseases and conditions, established the use of radiation dosimetry and the collaboration between physics and medicine and other significant practices. Sadly, Saul Hertz (a WWII veteran) died at a very young age.
About Dr. Saul Hertz
Dr. Saul Hertz (1905 – 1950) discovered the medical uses of radionuclides. His breakthrough work with radioactive iodine (RAI) created a dynamic paradigym change integrating the sciences. Radioactive iodine (RAI) is the first and Gold Standard of targeted cancer therapies. Saul Hertz’s research documents Hertz as the first and foremost person to conceive and develop the experimental data on RAI and apply it in the clinical setting.
Dr. Hertz was born to Orthodox Jewish immigrant parents in Cleveland, Ohio on April 20, 1905. He received his A.B. from the University of Michigan in 1925 with Phi Beta Kappa honors. He graduated from Harvard Medical School in 1929 at a time of quotas for outsiders. He fulfilled his internship and residency at Mt. Sinai Hospital in Cleveland. He came back to Boston in 1931 as a volunteer to join The Massachusetts General Hospital serving as the Chief of the Thyroid Unit from 1931 – 1943.
Two years after the discovery of artifically radioactivity, on November 12, 1936 Dr. Karl Compton, president of the Massachusetts Institute of Technology (MIT), spoke at Harvard Medical School. President Compton’s topic was What Physics can do for Biology and Medicine. After the presentation Dr. Hertz spontaneously asked Dr. Compton this seminal question, “Could iodine be made radioactive artificially?” Dr. Compton responded in writing on December 15, 1936 that in fact “iodine can be made artificially radioactive.”
Shortly thereafter, a collaboration between Dr. Hertz (MGH) and Dr. Arthur Roberts, a physicist of MIT, was established. In late 1937, Hertz and Roberts created and produced animal studies involving 48 rabbits that demonstrated that the normal thyroid gland concentrated Iodine 128 (non cyclotron produced), and the hyperplastic thyroid gland took up even more Iodine. This was a GIANT step for Nuclear Medicine.
In early 1941, Dr. Hertz administer the first therapeutic treatment of MIT Markle Cyclotron produced radioactive iodine (RAI) at the Massachusetts General Hospital. This led to the first series of twenty-nine patients with hyperthyroidism being treated successfully with RAI. ( see “Research” RADIOACTIVE IODINE IN THE STUDY OF THYROID PHYSIOLOGY VII The use of Radioactive Iodine Therapy in Hyperthyroidism, Saul Hertz and Arthur Roberts, JAMA Vol. 31 Number 2).
In 1937, at the time of the rabbit studies Dr Hertz conceived of RAI in therapeutic treatment of thyroid carsonoma. In 1942 Dr Hertz gave clinical trials of RAI to patients with thyroid carcinoma.
After serving in the Navy during World War II, Dr. Hertz wrote to the director of the Mass General Hospital in Boston, Dr. Paxon on March 12, 1946, “it is a coincidence that my new research project is in Cancer of the Thyroid, which I believe holds the key to the larger problem of cancer in general.”
Dr. Hertz established the Radioactive Isotope Research Institute, in September, 1946 with a major focus on the use of fission products for the treatment of thyroid cancer, goiter, and other malignant tumors. Dr Samuel Seidlin was the Associate Director and managed the New York City facilities. Hertz also researched the influence of hormones on cancer.
Dr. Hertz’s use of radioactive iodine as a tracer in the diagnostic process, as a treatment for Graves’ disease and in the treatment of cancer of the thyroid remain preferred practices. Saul Hertz is the Father of Theranostics.
Saul Hertz passed at 45 years old from a sudden death heart attack as documented by an autopsy. He leaves an enduring legacy impacting countless generations of patients, numerous institutions worldwide and setting the cornerstone for the field of Nuclear Medicine. A cancer survivor emailed, The cure delivered on the wings of prayer was Dr Saul Hertz’s discovery, the miracle of radioactive iodine. Few can equal such a powerful and precious gift.
To read and hear more about Dr. Hertz and the early history of RAI in diagnosing and treating thyroid diseases and theranostics see –
Hertz S, Roberts A. Radioactive iodine in the study of thyroid physiology. VII The use of radioactive iodine therapy in hyperthyroidism. J Am Med Assoc 1946;131:81-6.
Hertz S. A plan for analysis of the biologic factors involved in experimental carcinogenesis of the thyroid by means of radioactive isotopes. Bull New Engl Med Cent 1946;8:220-4.
Thrall J. The Story of Saul Hertz, Radioiodine and the Origins of Nuclear Medicine. Available from: http://www.youtube.com/watch?v=34Qhm8CeMuc. [Last accessed on 2018 Dec 01].
Krolicki L, Morgenstern A, Kunikowska J, Koiziar H, Krolicki B, Jackaniski M, et al. Glioma Tumors Grade II/III-Local Alpha Emitters Targeted Therapy with 213 Bi-DOTA-Substance P, Endocrine Abstracts. Vol. 57. Society of Nuclear Medicine and Molecular Imaging; 2016. p. 632.
Baum RP, Kulkarni HP. Duo PRRT of neuroendocrine tumours using concurrent and sequential administration of Y-90- and Lu-177-labeled somatostatin analogues. In: Hubalewska-Dydejczyk A, Signore A, de Jong M, Dierckx RA, Buscombe J, Van de Wiel CJ, editors. Somatostatin Analogues from Research to Clinical Practice. New York: Wiley; 2015.
Early Details of Brain Damage in COVID-19 Patients
Reporter: Irina Robu, PhD
COVID-19 has currently claimed more American lives than World War I, Vietnam War and the Korean war combined. And while it is mainly a respiratory disease, COVID-19 infection affects other organs, including the brain. Researchers at Harvard-affiliated Massachusetts General Hospital found that COVID patients with neurological symptoms show more than some metabolic disturbances in the brain as patients who have suffered oxygen deprivation.
During the course of the pandemic, thousand patients with COVID-19 have been seen at MGH and the severity of the neurological symptoms varies from temporary loss of smell to more severe symptoms such as dizziness, confusion, seizures, and stroke. According to the principal investigator of the study, Eva Maria Ratai, Department of Radiology used 3 Tesla Magnetic Resonance Spectroscopy (MRS) to identify neurochemical abnormalities even the structural imagining findings are normal. COVID-19 patients’ brains showed N-acetyl-aspartate (NAA) reduction, choline elevation, and myo-inositol elevation, comparable to what is seen with these metabolites in other patients with leukoencephalopathy after hypoxia without COVID.
Their research indicated that one of patients with COVID-19 indicate the most severe white matter damage, whereas another had COVID-19 associated necrotizing leukoencephalopathy at the time of imaging. And the patient that experience cardiac arrest showed subtle white matter changes on structural MR. The control cases included one patient with damage due to hypoxia from other causes: one with sepsis-related white matter damage, and a normal, age-matched, healthy volunteer.
The main question still remains whether the decrease in the oxygen of the brain is causing the white matter to change or whether the virus itself is attacking white matter. The conclusion is that MRS can be used as a disease and therapy monitoring tool.
Indeed, many viruses can cause inflammation and weakening of the heart.
So far there is no established action to take for prevention, and management is based on clinical manifestations of heart failure: shortness of breath, particularly if worse laying flat or worse with exertion, leg swelling (edema), blood tests showing elevated brain natriuretic peptide (BNP or proBNP, a marker of heart muscle strain), and a basic metabolic panel that may show “pre-renal azotemia” (elevation of BUN and Creatinine, typically in a ratio >20:1) and/or hyponatremia (sodium concentration below 135 mEq/dL). If any of the above are suspected, it is reasonable to get transthoracic echocardiography for systolic and diastolic function. If either systolic or diastolic function by ultrasound show significant impairment not improved by usual therapy (diuretic, ACEI/ARB/ARNI, blocker, aldosterone inhibitor e.g. spironolactone) then an MRI scar map may be considered (MRI scar maps show retention of gadolinium contrast agent by injured heart muscle, first demonstrated by Dr. Justin Pearlman during angiogenesis research MRI studies).
There is no controversy in the above, the controversy is a rush to expanded referral for cardiac MRI without clear clinical evidence of heart impairment, at a stage when there is no established therapy for possible detection of myocarditis (cardiac inflammation). General unproven measures for inflammation may include taking ginger and tumeric supplements if well tolerated by the stomach, drinking 2 cups/day of Rooibos Tea if well tolerated by the liver.
Canakinumab was recommended by one research group to treat inflammation and risk to the heart if the blood test hsCRP is elevated (in addition to potential weakening of muscle, inflammation activates complement, makes atherosclerosis lesions unstable, and thus may elevate risk of heart attack, stroke, renal failure or limb loss from blocked blood delivery). The canakinumab studies were published in NEJM and LANCET with claims of significant improvement in outcomes, but that was not approved by FDA or confirmed by other groups, even though it has biologic plausibility. https://www.thelancet.com/journals/lancet/article/PIIS0140-67361732247-X/fulltext
Some Heart Societies Agree on Cautions for COVID-Myocarditis Screening
— Official response has been modest, though
by Crystal Phend, Senior Editor, MedPage Today September 18, 2020
Such evidence of myocardial injury and inflammation on CMR turned up in a German study among people who recovered from largely mild or moderate cases of COVID-19 compared with healthy controls and risk factor-matched controls.
Then an Ohio State University study showed CMR findings suggestive of myocarditis in 15% of collegiate athletes after asymptomatic or mild SARS-CoV-2 infection.
But an open letter from some 50 medical professionals across disciplines emphasized that “prevalence, clinical significance and long-term implications” of such findings aren’t known. The letter called on the 18 professional societies to which it was sent on Tuesday to release clear guidance against CMR screening in the general population to look for post-COVID heart damage in the absence of symptoms.
The Society for Cardiac Magnetic Resonance quickly responded with a brief statement from its chief executive officer, Chiara Bucciarelli-Ducci, MD, PhD, agreeing that routine CMR in asymptomatic patients after COVID-19 “is currently not justified… and it should not be encouraged.”
She referred clinicians to the multisociety guidelines on clinical indications of CMR when deciding whether to scan COVID-19 patients. “While CMR is an excellent imaging tool for diagnosing myocarditis in patients with suspected disease, we do not recommend its use in patients without symptoms,” she added.
The American Heart Association didn’t put out any written statement but offered spokesperson Manesh Patel, MD, chair of its Diagnostic and Interventional Cath Committee.
“The American Heart Association’s position on this is that in general we agree that routine cardiac MRI should not be conducted unless in the course of a study” for COVID-19 patients, he said. “There’s a lot of evolving information around people with COVID, and certainly asymptomatic status, whether it’s recent or prior, it’s not clearly known what the MRI findings will mean or what the long-term implications are without both a control group and an understanding around population.”
The ACC opted against taking a stand. It provided MedPage Today with the following statement from ACC President Athena Poppas, MD:
“We appreciate the authors’ concerns about the potential mischaracterization of the long-term impact of myocarditis after a COVID-19 diagnosis and the need for well-designed clinical trials and careful, long term follow-up. The pandemic is requiring everyone make real-time decisions on how to best care for heart disease patients who may be impacted by COVID-19. The ACC is committed to helping synthesize and provide the most up-to-date, high quality information possible to the cardiovascular care team. We will continue to review and assess the scientific data surrounding cardiac health and COVID-19 and issue guidance to help our care team.”
While the open letter noted that some post-COVID patients have been asking for CMR, Walsh noted that primary care would likely see the brunt of any such influx. She personally has not had any patients ask to be screened.
Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial
Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence.
Methods
We did a randomised, double-blind, placebo-controlled trial of canakinumab in 10 061 patients with atherosclerosis who had had a myocardial infarction, were free of previously diagnosed cancer, and had concentrations of high-sensitivity C-reactive protein (hsCRP) of 2 mg/L or greater. To assess dose–response effects, patients were randomly assigned by computer-generated codes to three canakinumab doses (50 mg, 150 mg, and 300 mg, subcutaneously every 3 months) or placebo. Participants were followed up for incident cancer diagnoses, which were adjudicated by an oncology endpoint committee masked to drug or dose allocation. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT01327846. The trial is closed (the last patient visit was in June, 2017).
Findings
Baseline concentrations of hsCRP (median 6·0 mg/L vs 4·2 mg/L; p<0·0001) and interleukin 6 (3·2 vs 2·6 ng/L; p<0·0001) were significantly higher among participants subsequently diagnosed with lung cancer than among those not diagnosed with cancer. During median follow-up of 3·7 years, compared with placebo, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26–41% and of interleukin 6 of 25–43% (p<0·0001 for all comparisons). Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group (p=0·0007 for trend across groups), but was significantly lower than placebo only in the 300 mg group individually (hazard ratio [HR] 0·49 [95% CI 0·31–0·75]; p=0·0009). Incident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0·61 [95% CI 0·39–0·97]; p=0·034) and 300 mg groups (HR 0·33 [95% CI 0·18–0·59]; p<0·0001; p<0·0001 for trend across groups). Lung cancer mortality was significantly less common in the canakinumab 300 mg group than in the placebo group (HR 0·23 [95% CI 0·10–0·54]; p=0·0002) and in the pooled canakinumab population than in the placebo group (p=0·0002 for trend across groups). Fatal infections or sepsis were significantly more common in the canakinumab groups than in the placebo group. All-cause mortality did not differ significantly between the canakinumab and placebo groups (HR 0·94 [95% CI 0·83–1·06]; p=0·31).
Interpretation
Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Replication of these data in formal settings of cancer screening and treatment is required.
3D printing is a fabrication technique used to transform digital objects into physical models, which builds structures of arbitrary geometry by depositing material in successive layers on the basis of specific digital design. Even though, the use of 3D bioprinting in cardiovascular medicine is relatively new development, advancement within this discipline is occurring at such a rapid rate. Most cardiologists believed the costs would be too high for routine use such that the price tag was better for academic applications.
Now as the prices are starting to lower, the idea of using 3D printed models of organs vessels and tissue manufactured based on CT, MRI and echocardiography might be beneficial according to Dr. Fadi Matar, professor at University of South Florida. He and his cardiology colleagues use 3D printed models to allow them to view patient’s complex anatomies before deciding what treatments to pursue. The models allow them to calculate the size and exact placement of devices which has led to shorter procedure time and better outcome.
In a study published in Academic Radiology, David Ballard, professor at University School of Medicine appraised the costs of setting up a 3D printing lab including the commercial printer plus software, lab space, materials and staffing. According to Ballard’s team, the commercial printers start at $12,000 but can be as high as high as $500,000.
According to American Medical Association-approved Category III Current Procedural Terminology (CPT) codes allows cardiology relief from setting up a new 3D printing lab such as Codes 0559T and 0560T, for individually prepared 3D-printed anatomical models with one or more components (including arteries and veins) and Codes 0561T and 0562T, which are for the production of personalized 3D-printed cutting or drilling tools that use patient imaging data and often are used to guide or facilitate surgery.
These codes have been met with enthusiasm by teams eyeing 3D printing, but there are noteworthy limitations to Category III codes—which are temporary codes describing emerging technologies, services and procedures that are used for tracking effectiveness data. It is important to note that Category III codes are not reimbursed but often are a step toward reimbursement.
New and improved materials also might lead to a sharper focus on 3D printing in cardiology. Dr. Fadi Matar says companies are working on materials that better mimic elements of the heart. Such “mimicry” ought to enhance the value of 3D-printed models since they will give cardiologists more realistic insights into how specific devices will interact with an individual patient’s heart. Even with the complex modalities of using 3D bioprinting, in time there would be less obstacles to being able to set up a 3D bioprinter lab.
References in 
2012pharmaceutical
sjwilliamspa