Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, co-led the Telomere-to-Telomere (T2T) Consortium, which has released the first complete, gapless assembly of a human genome sequence. (Photo by Carolyn Lagattuta)
The first truly complete sequence of a human genome, covering each chromosome from end to end with no gaps and unprecedented accuracy, is now accessible through the UCSC Genome Browser and is described in six papers published March 31 in Science.
Since the first working draft of a human genome sequence was assembled at UC Santa Cruz in 2000, genomics research has led to enormous advances in our understanding of human biology and disease. Nevertheless, crucial regions accounting for some 8% of the human genome have remained hidden from scientists for over 20 years due to the limitations of DNA sequencing technologies.
“Ever since we had the first draft human genome sequence, determining the exact sequence of complex genomic regions has been challenging,” said Evan Eichler, Ph.D., researcher at the University of Washington School of Medicine and T2T consortium co-chair. “I am thrilled that we got the job done. The complete blueprint is going to revolutionize the way we think about human genomic variation, disease and evolution.”
Telomere-to-Telomere Consortium
The sequencing and analysis were performed by a team of more than 100 people, the so-called Telemere-to-Telomere Consortium, or T2T, named for the telomeres that cap the ends of all chromosomes. T2T was initially set up in 2019 by Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, and Adam Phillippy at the National Human Genome Research Institute (NHGRI).
The consortium’s gapless version of all 22 autosomes and the X sex chromosome is composed of 3.055 billion base pairs, the units from which chromosomes and our genes are built, and 19,969 protein-coding genes.
The new reference genome, called T2T-CHM13, adds nearly 200 million base pairs of novel DNA sequences, including 99 genes likely to code for proteins and nearly 2,000 candidate genes that need further study. It also corrects thousands of structural errors in the current reference sequence.
Complete sequence of a Y chromosome
The researchers also released this week the complete sequence of a Y chromosome from a different source, which took nearly as long to assemble as the rest of the genome combined, said Nicolas Altemose, a postdoctoral fellow at the University of California, Berkeley, and a co-author of four new papers about the completed genome. The analysis of this new Y chromosome sequence will appear in a future publication.
“In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their health care,” said Phillippy, one of the leaders of T2T and a senior investigator at NHGRI. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.”
The gaps now filled by the new sequence include the entire short arms of five human chromosomes and cover some of the most complex regions of the genome. These include highly repetitive DNA sequences found in and around important chromosomal structures such as the telomeres at the ends of chromosomes and the centromeres that coordinate the separation of replicated chromosomes during cell division.
New discoveries
The new DNA sequences reveal never-before-seen detail about the region around the centromere. Variability within this region may also provide new evidence of how our human ancestors evolved in Africa.
“Uncovering the complete sequence of these formerly missing regions of the genome told us so much about how they’re organized, which was totally unknown for many chromosomes,” said Altemose. “Before, we just had the blurriest picture of what was there, and now it’s crystal clear down to single base pair resolution.”
The new sequence also reveals previously undetected segmental duplications, long stretches of DNA that are duplicated in the genome and are known to play important roles in evolution and disease.
“These parts of the human genome that we haven’t been able to study for 20-plus years are important to our understanding of how the genome works, genetic diseases, and human diversity and evolution,” Miga said.
Many of the newly revealed regions have important functions in the genome even if they do not include active genes.
What they found in and around the centromeres were layers of new sequences overlaying layers of older sequences, as if through evolution new centromere regions have been laid down repeatedly to bind to the kinetochore. The older regions are characterized by more random mutations and deletions, indicating they’re no longer used by the cell. The newer sequences where the kinetochore binds are much less variable, and also less methylated. The addition of a methyl group is an epigenetic tag that tends to silence genes.
All of the layers in and around the centromere are composed of repetitive lengths of DNA, based on a unit about 171 base pairs long, which is roughly the length of DNA that wraps around a group of proteins to form a nucleosome, keeping the DNA packaged and compact. These 171 base pair units form even larger repeat structures that are duplicated many times in tandem, building up a large region of repetitive sequences around the centromere.
DNA sequences around the centromere could also be used to trace human lineages back to our common ape ancestors, he noted.
“As you move away from the site of the active centromere, you get more and more degraded sequence, to the point where if you go out to the furthest shores of this sea of repetitive sequences, you start to see the ancient centromere that, perhaps, our distant primate ancestors used to bind to the kinetochore,” Altemose said. “It’s almost like layers of fossils.”
Seeing the whole genome as a complete system for the first time
“There is a profound advantage to seeing the whole genome as a complete system. It puts us in a position to unravel how that system works,” said David Haussler, director of the UC Santa Cruz Genomics Institute. “We’ve gotten an enormous understanding of human biology and disease from having roughly 90 percent of the human genome, but there were many important aspects that lay hidden, out of view of science, because we did not have the technology to read those portions of the genome. Now we can stand at the top of the mountain and see all of the landscape below and get a complete picture of our human genetic heritage.”
The T2T genome sequence, representing the finished CHM13 genome plus the recently finished T2T Y chromosome (CHM13 includes an X but not a Y chromosome), is now a new reference genome in the UCSC Genome Browser. The T2T sequence is fully annotated in the browser, providing an efficient way for scientists to access and visualize a wealth of information associated with genes and other elements of the genome.
“We wanted to put the information out in a way that is accessible and familiar to researchers so they can begin to build on it and use all the tools and resources the browser provides,” Miga explained.
Genome Reference Consortium
The new T2T reference genome will complement the standard human reference genome, known as Genome Reference Consortium build 38 (GRCh38), which had its origins in the publicly funded Human Genome Project and has been continually updated since the first draft in 2000.
“We’re adding a second complete genome, and then there will be more,” explained Haussler. “The next phase is to think about the reference for humanity’s genome as not being a single genome sequence. This is a profound transition, the harbinger of a new era in which we will eventually capture human diversity in an unbiased way.”
Human Pangenome Reference Consortium
The T2T Consortium has now joined with the Human Pangenome Reference Consortium, which aims to create a new “human pangenome reference” based on the complete genome sequences of 350 individuals.
“Pangenomics is about capturing the diversity of the human population, and it’s also about ensuring we’ve captured the whole genome properly,” said Benedict Paten, associate professor of biomolecular engineering at UCSC’s Baskin School of Engineering, a coauthor of the T2T papers, and a leader of the pangenomics effort. “Without having a map of these difficult-to-sequence regions of the genome across multiple individuals, then we’re missing a huge amount of the variation present in our population. T2T sets us up to look across hundreds of genomes from telomere to telomere. It’s going to be great!”
The standard reference genome (GRCh38) does not represent any one individual but was assembled from multiple donors. Merging them into one linear sequence created artificial structures in the sequence. The Human Pangenome Project will make it possible to compare newly sequenced genomes to multiple complete genomes representing a range of human ancestries.
More accurate assessments of genetic variants
An important outcome of the new T2T sequence is enabling more accurate assessments of genetic variants. When human genomes are sequenced for clinical studies to understand the role of genetic variants in disease or to study genetic diversity within and between human populations, they are nearly always analyzed by aligning the sequencing results with the reference genome for comparison. The T2T variant team documented major improvements in identifying and interpreting genetic variants using the new T2T sequence compared to the standard human reference genome.
“The new human genome is incredibly accurate at the base level, allowing us to flag hundreds of thousands of variants that had been misinterpreted by mapping them to the standard reference. Many of these new variants are in genes known to contribute to disease. We can now spot those because we have a more complete and accurate reference genome,” Miga said.
Miga’s research has focused on satellite DNA, the long stretches of repetitive DNA sequences found mostly in and around telomeres and centromeres. The centromeres separate each chromosome into a short arm and a long arm and hold duplicated chromosomes together prior to cell division.
“The centromeres play a critical role in how chromosomes segregate properly during cell division, and we’ve known for some time now that they are misregulated in all kinds of human diseases. But we’ve never been able to study them at the sequence level,” Miga said. “By far the largest portion of new sequences added to the reference are centromere satellite DNAs. For the first time, we can study ‘base-by-base’ the sequences that define the centromere and can start to understand how it works.”
Long-read sequencing a game changer
The T2T’s success is due to improved techniques for sequencing long stretches of DNA at once, which helps when determining the order of highly repetitive stretches of DNA. Among these are PacBio’s HiFi sequencing, which can read lengths of more than 20,000 base pairs with high accuracy. Technology developed by Oxford Nanopore Technologies, on the other hand, can read up to several million base pairs in sequence, though with less fidelity. For comparison, so-called next-generation sequencing by Illumina is limited to hundreds of base pairs.
“These new long-read DNA sequencing technologies are just incredible; they’re such game changers, not only for this repetitive DNA world, but because they allow you to sequence single long molecules of DNA,” Altemose said. “You can begin to ask questions at a level of resolution that just wasn’t possible before, not even with short-read sequencing methods.”
———
Karen Miga
Miga is a co-corresponding author of the main Science paper along with Adam Phillippy at NHGRI and Evan Eichler at the University of Washington:
She is also a co-corresponding author of the papers on:
and a coauthor of the papers on:
—————-
The t2t working group
https://sites.google.com/ucsc.edu/t2tworkinggroup
New ultrasound imaging technique accurately identifies atherosclerotic plaque volume
, /in Featured Articles /by panglobalA new imaging technique for real 3D vascular ultrasound could become a key tool in strategies aimed at preventing cardiovascular disease in apparently healthy persons, complementing traditional risk parameters, such as cholesterol and high blood pressure. The new results, published in JACC: Cardiovascular Imaging [1] show that real 3D vascular ultrasound is reliable, accurate, and […]
In major breakthrough, scientists complete first gapless sequence of a human genome, reveal hidden regions
, /in Editors' Picks, Featured Articles /by panglobalKaren Miga, assistant professor of biomolecular engineering at UC Santa Cruz, co-led the Telomere-to-Telomere (T2T) Consortium, which has released the first complete, gapless assembly of a human genome sequence. (Photo by Carolyn Lagattuta)
The first truly complete sequence of a human genome, covering each chromosome from end to end with no gaps and unprecedented accuracy, is now accessible through the UCSC Genome Browser and is described in six papers published March 31 in Science.
Since the first working draft of a human genome sequence was assembled at UC Santa Cruz in 2000, genomics research has led to enormous advances in our understanding of human biology and disease. Nevertheless, crucial regions accounting for some 8% of the human genome have remained hidden from scientists for over 20 years due to the limitations of DNA sequencing technologies.
“Ever since we had the first draft human genome sequence, determining the exact sequence of complex genomic regions has been challenging,” said Evan Eichler, Ph.D., researcher at the University of Washington School of Medicine and T2T consortium co-chair. “I am thrilled that we got the job done. The complete blueprint is going to revolutionize the way we think about human genomic variation, disease and evolution.”
Telomere-to-Telomere Consortium
The sequencing and analysis were performed by a team of more than 100 people, the so-called Telemere-to-Telomere Consortium, or T2T, named for the telomeres that cap the ends of all chromosomes. T2T was initially set up in 2019 by Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, and Adam Phillippy at the National Human Genome Research Institute (NHGRI).
The consortium’s gapless version of all 22 autosomes and the X sex chromosome is composed of 3.055 billion base pairs, the units from which chromosomes and our genes are built, and 19,969 protein-coding genes.
The new reference genome, called T2T-CHM13, adds nearly 200 million base pairs of novel DNA sequences, including 99 genes likely to code for proteins and nearly 2,000 candidate genes that need further study. It also corrects thousands of structural errors in the current reference sequence.
Complete sequence of a Y chromosome
The researchers also released this week the complete sequence of a Y chromosome from a different source, which took nearly as long to assemble as the rest of the genome combined, said Nicolas Altemose, a postdoctoral fellow at the University of California, Berkeley, and a co-author of four new papers about the completed genome. The analysis of this new Y chromosome sequence will appear in a future publication.
“In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their health care,” said Phillippy, one of the leaders of T2T and a senior investigator at NHGRI. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.”
The gaps now filled by the new sequence include the entire short arms of five human chromosomes and cover some of the most complex regions of the genome. These include highly repetitive DNA sequences found in and around important chromosomal structures such as the telomeres at the ends of chromosomes and the centromeres that coordinate the separation of replicated chromosomes during cell division.
New discoveries
The new DNA sequences reveal never-before-seen detail about the region around the centromere. Variability within this region may also provide new evidence of how our human ancestors evolved in Africa.
“Uncovering the complete sequence of these formerly missing regions of the genome told us so much about how they’re organized, which was totally unknown for many chromosomes,” said Altemose. “Before, we just had the blurriest picture of what was there, and now it’s crystal clear down to single base pair resolution.”
The new sequence also reveals previously undetected segmental duplications, long stretches of DNA that are duplicated in the genome and are known to play important roles in evolution and disease.
“These parts of the human genome that we haven’t been able to study for 20-plus years are important to our understanding of how the genome works, genetic diseases, and human diversity and evolution,” Miga said.
Many of the newly revealed regions have important functions in the genome even if they do not include active genes.
What they found in and around the centromeres were layers of new sequences overlaying layers of older sequences, as if through evolution new centromere regions have been laid down repeatedly to bind to the kinetochore. The older regions are characterized by more random mutations and deletions, indicating they’re no longer used by the cell. The newer sequences where the kinetochore binds are much less variable, and also less methylated. The addition of a methyl group is an epigenetic tag that tends to silence genes.
All of the layers in and around the centromere are composed of repetitive lengths of DNA, based on a unit about 171 base pairs long, which is roughly the length of DNA that wraps around a group of proteins to form a nucleosome, keeping the DNA packaged and compact. These 171 base pair units form even larger repeat structures that are duplicated many times in tandem, building up a large region of repetitive sequences around the centromere.
DNA sequences around the centromere could also be used to trace human lineages back to our common ape ancestors, he noted.
“As you move away from the site of the active centromere, you get more and more degraded sequence, to the point where if you go out to the furthest shores of this sea of repetitive sequences, you start to see the ancient centromere that, perhaps, our distant primate ancestors used to bind to the kinetochore,” Altemose said. “It’s almost like layers of fossils.”
Seeing the whole genome as a complete system for the first time
“There is a profound advantage to seeing the whole genome as a complete system. It puts us in a position to unravel how that system works,” said David Haussler, director of the UC Santa Cruz Genomics Institute. “We’ve gotten an enormous understanding of human biology and disease from having roughly 90 percent of the human genome, but there were many important aspects that lay hidden, out of view of science, because we did not have the technology to read those portions of the genome. Now we can stand at the top of the mountain and see all of the landscape below and get a complete picture of our human genetic heritage.”
The T2T genome sequence, representing the finished CHM13 genome plus the recently finished T2T Y chromosome (CHM13 includes an X but not a Y chromosome), is now a new reference genome in the UCSC Genome Browser. The T2T sequence is fully annotated in the browser, providing an efficient way for scientists to access and visualize a wealth of information associated with genes and other elements of the genome.
“We wanted to put the information out in a way that is accessible and familiar to researchers so they can begin to build on it and use all the tools and resources the browser provides,” Miga explained.
Genome Reference Consortium
The new T2T reference genome will complement the standard human reference genome, known as Genome Reference Consortium build 38 (GRCh38), which had its origins in the publicly funded Human Genome Project and has been continually updated since the first draft in 2000.
“We’re adding a second complete genome, and then there will be more,” explained Haussler. “The next phase is to think about the reference for humanity’s genome as not being a single genome sequence. This is a profound transition, the harbinger of a new era in which we will eventually capture human diversity in an unbiased way.”
Human Pangenome Reference Consortium
The T2T Consortium has now joined with the Human Pangenome Reference Consortium, which aims to create a new “human pangenome reference” based on the complete genome sequences of 350 individuals.
“Pangenomics is about capturing the diversity of the human population, and it’s also about ensuring we’ve captured the whole genome properly,” said Benedict Paten, associate professor of biomolecular engineering at UCSC’s Baskin School of Engineering, a coauthor of the T2T papers, and a leader of the pangenomics effort. “Without having a map of these difficult-to-sequence regions of the genome across multiple individuals, then we’re missing a huge amount of the variation present in our population. T2T sets us up to look across hundreds of genomes from telomere to telomere. It’s going to be great!”
The standard reference genome (GRCh38) does not represent any one individual but was assembled from multiple donors. Merging them into one linear sequence created artificial structures in the sequence. The Human Pangenome Project will make it possible to compare newly sequenced genomes to multiple complete genomes representing a range of human ancestries.
More accurate assessments of genetic variants
An important outcome of the new T2T sequence is enabling more accurate assessments of genetic variants. When human genomes are sequenced for clinical studies to understand the role of genetic variants in disease or to study genetic diversity within and between human populations, they are nearly always analyzed by aligning the sequencing results with the reference genome for comparison. The T2T variant team documented major improvements in identifying and interpreting genetic variants using the new T2T sequence compared to the standard human reference genome.
“The new human genome is incredibly accurate at the base level, allowing us to flag hundreds of thousands of variants that had been misinterpreted by mapping them to the standard reference. Many of these new variants are in genes known to contribute to disease. We can now spot those because we have a more complete and accurate reference genome,” Miga said.
Miga’s research has focused on satellite DNA, the long stretches of repetitive DNA sequences found mostly in and around telomeres and centromeres. The centromeres separate each chromosome into a short arm and a long arm and hold duplicated chromosomes together prior to cell division.
“The centromeres play a critical role in how chromosomes segregate properly during cell division, and we’ve known for some time now that they are misregulated in all kinds of human diseases. But we’ve never been able to study them at the sequence level,” Miga said. “By far the largest portion of new sequences added to the reference are centromere satellite DNAs. For the first time, we can study ‘base-by-base’ the sequences that define the centromere and can start to understand how it works.”
Long-read sequencing a game changer
The T2T’s success is due to improved techniques for sequencing long stretches of DNA at once, which helps when determining the order of highly repetitive stretches of DNA. Among these are PacBio’s HiFi sequencing, which can read lengths of more than 20,000 base pairs with high accuracy. Technology developed by Oxford Nanopore Technologies, on the other hand, can read up to several million base pairs in sequence, though with less fidelity. For comparison, so-called next-generation sequencing by Illumina is limited to hundreds of base pairs.
“These new long-read DNA sequencing technologies are just incredible; they’re such game changers, not only for this repetitive DNA world, but because they allow you to sequence single long molecules of DNA,” Altemose said. “You can begin to ask questions at a level of resolution that just wasn’t possible before, not even with short-read sequencing methods.”
———
Karen Miga
Miga is a co-corresponding author of the main Science paper along with Adam Phillippy at NHGRI and Evan Eichler at the University of Washington:
She is also a co-corresponding author of the papers on:
and a coauthor of the papers on:
—————-
The t2t working group
https://sites.google.com/ucsc.edu/t2tworkinggroup
Cleveland Clinic opens state-of-the-art hospital in London
, /in E-News /by panglobalCleveland Clinic London exterior
Cleveland Clinic opened their Cleveland Clinic London Hospital on 29 March. The 184-bed state-of-the-art hospital, at 33 Grosvenor Place in central London is the newest location in Cleveland Clinic’s expanding global footprint and the second in London, following the opening of Cleveland Clinic Portland Place Outpatient Centre in September 2021.
As part of one of the world’s top hospital systems – as determined in Newsweek’s World’s Best Hospitals 2022 list – Cleveland Clinic London provides patients access to a global network of physicians and specialists to provide the highest quality care, as well as world-class patient experience built around the best practices and core values of Cleveland Clinic. It will offer a doctor-led model of care that is innovative, empathetic and based on research and education.
The eight-story facility will treat a wide range of complex conditions, with a focus on heart and vascular, digestive disease, neurosciences and orthopaedics. The hospital has 184 inpatient beds, including 29 ICU beds and eight operating theatres, a 41-bed neurological rehabilitation ward and a staff of approximately 1,150 caregivers.
Cleveland Clinic London patient room
Patient safety and experience
Equipped with the latest technology, Cleveland Clinic London has the ability to care for a complex patient population, supported by an acute admissions unit and 24/7 intensive care specialists in the ICU, a model that enhances patient safety and experience. Alongside its core focus areas, the hospital also offers a full range of medical sub-specialties and comprehensive services for imaging, labs and interventional radiology.
The Cleveland Clinic health system, which employs more than 72,000 caregivers worldwide, has pioneered many medical breakthroughs, including coronary artery bypass surgery, the first face transplant in the United States, and most recently the first uterus transplant in the United States.
Cleveland Clinic London Hybrid Operating Room
“For more than 100 years, Cleveland Clinic has been at the forefront of medical innovation and specialized health care,” said Tom Mihaljevic, M.D., Cleveland Clinic CEO and President. “We believe that touching more lives is our ethical imperative. With the opening of Cleveland Clinic London, we are extending our unique model of care to more patients than ever.”
Brian Donley, M.D., CEO of Cleveland Clinic London, said: “This is an eventful moment for the entire Cleveland Clinic family. We are excited to be bringing our unique model of care to the U.K., combining London’s world-renowned physicians and research with Cleveland Clinic’s 100-year history of technological advances and clinical expertise. We will provide patients with an unparalleled experience and the highest quality care.”
Cleveland Clinic London ICU
Cleveland Clinic’s latest facility combines the health system’s integrated care approach with its leadership in medical innovation to meet the unique needs of each patient. The hospital is equipped with the most advanced medical and surgical technologies, including innovative laser and robotic surgery capabilities. It will offer the most advanced minimally invasive procedures, such as transcatheter aortic valve implantations (TAVI); Cleveland Clinic was one of the early pioneering centres of TAVI and has since become a world leader in this specialized treatment.
Intraoperative imaging
Cleveland Clinic London is one of the first private hospitals in the U.K. that can conduct intraoperative imaging for brain and spinal cord disorders, a leading tool in preventing reoperations. The hospital is also equipped with a 41-bed neuro-rehabilitation suite with technologically advanced robotic equipment.
Cleveland Clinic London is also the first U.K. hospital to use advanced technology such as pharmacy barcoding and robot-powered medicine administration tracking, offering an additional level of safety in the delivery of medicine. Patients and caregivers will have access to the most advanced electronic medical records, allowing caregivers to make faster and more effective decisions about patient care, and giving the patient easier access to information about their treatment.
Cleveland Clinic London Operating Room
Comprehensive data publication
Cleveland Clinic is among the first hospitals in the United States to publish outcomes. Since 2004, it has required all clinical specialties to collect and publish comprehensive data every year. In 2008, the health system was the first to disclose industry relationships of its clinicians and again, in 2015, Cleveland Clinic was the first medical center to display patients’ ratings and comments about the care they receive. Cleveland Clinic London will report data and outcomes to key U.K. national registries. The hospital will publish detailed information on its treatment outcomes, with the goal of helping existing and future patients make informed decisions about their care options.
Virtual video tours of Cleveland Clinic London
International Hospital Federation Awards 2022 now open for entries
, /in E-News, Events /by panglobalThe IHF Awards are recognized around the world as the premier awards programme to honour hospitals and healthcare organizations.
In its seventh year, the International Hospital Federation Awards 2022 (IHF Awards) return to recognize the excellence and outstanding achievements of hospitals and health service providers around the globe.
A new category — American Hospital Association Excellence Award for Healthcare Workers’ Wellbeing – has been added to honour initiatives by hospitals to support their workforce. Workforce wellbeing had been much talked about even before COVID-19, and the pandemic has made this even more relevant. Many hospitals around the world have started initiatives and efforts to support their workforce. The IHF Awards deem it important to recognize and honour these initiatives.
Entries are now being accepted for the following award categories:
Submission Criteria and entries
Learn about the Categories, the Submission Criteria and submit your entry here: https://worldhospitalcongress.org/awards/
Entries must be submitted through the IHF online submission platform. Nominations will be accepted until 31 May.
The awards will be presented to the winners at a special Awards Ceremony at the 45th IHF World Hospital Congress which will be held on 9-11 November in Dubai, UAE
MEDICAL JAPAN Tokyo in October, 2022!
, /in Events /by 3wmediaJapan re-opened its borders! Are you interested in finding importers and expanding business in Japan? Join us at MEDICAL JAPAN Tokyo in October, 2022!
Interview: International Hospital speaks to PENTAX Medical about their new focus on ‘Power of Choice’
, /in Editors' Picks, Featured Articles /by panglobalHarald Huber, Global VP for Product and Category Management at Pentax Medical
International Hospital’s Twan Heesakkers speaks to Harald Huber, Global VP for Product and Category Management at PENTAX Medical, about the company’s new single-use bronchoscope, what they are focusing on this year and the ‘Power of Choice’.
Twan Heesakkers: What new products are you bringing to the market this year?
Harald Huber: This year we will bring a couple of new things to the market. We would like to put more emphasis on the [PENTAX Medical] ONE Pulmo, by creating more public awareness of the product. The ONE Pulmo is a single-use bronchoscope, our first product in the single-use area. We also have the PlasmaTYPHOON+, our unique solution for endoscope drying and storage, which we will also push forward. Furthermore, we are working very hard on providing innovative solutions, instead of following the traditional way the endoscope business was set up, which was more into products and endoscopic processors. We want to bring our way of thinking forward, which is more focussed on developing solutions rather than pure product business. So we want to interconnect these things, for example the PlasmaTYPHOON+ is part of our hygiene commitment. We are calling this the ‘Power of Choice’. This Power of Choice will also apply to our single-use endoscopes and has a compelling advantage for our customers. The idea behind ‘Power of Choice’ is that we do not want to dictate to our customers what kind of procedure they have to do. We want to allow them the highest possible freedom to pick the right equipment for their procedure. That’s why we want to offer as many solutions as possible in different areas and move away from the traditional thinking about products.
The PENTAX Medical ONE Pulmo single-use bronchoscope.
TH: You mentioned the single-use bronchoscope – the PENTAX Medical ONE Pulmo for which you received the CE mark last year? Can you tell us a little more about this product; what sets it apart from similar competitors’ products?
HH: When we came up with this solution we thought, ‘if we, as PENTAX Medical, come up with a single-use bronchoscope how will it be different?’ As you know, our company produces reusable products and everybody will ask, why are we coming up with a single-use bronchoscope? And that’s again in line with our idea of providing the Power of Choice. So the difference, I think, to other single-use bronchoscopes that you see on the market is that this is probably the first one that is purely developed by an endoscope company. So, with our expertise in image development we were able to develop a camera in such a way that on one side its single-use, while on the other side it can provide comparable image quality to our reusable scopes. This is kind of the red line throughout the whole design process and differentiates us from the competition. It also continues with the design of the control body, with the handle actually. We want to provide a real Power of Choice. Doctors should not have to care if they use the single-use scope or the reusable one. They want to have the same familiar touch and feel that they are used to when doing an endoscopy procedure. That’s why we mimic the reusable scope, so it has the same properties of a reusable scope, and we develop it in such a way that it can be offered as a single-use solution.
The PENTAX Medical ONE Pulmo is a single-use bronchoscope with superior suction power and HD image quality. The sterile-packed scopes are ready to use. Manoeuvrability and device insertion are easy and intuitive, creating a seamless user experience.
TH: Besides offering the ‘Power of Choice’, what other reasons are behind PENTAX Medical choosing to develop a single-use disposable bronchoscope?
HH: ‘Choice’ is an important factor as to why we did this. The other thing is that there is of course concern about contamination. There are special patient populations where it definitely makes sense to go for a single-use scope. We know that it does not make sense for all patient populations. Also, you have the sustainability factor, you have the cost of cleaning, pricing of the product, etc. There are multiple factors which tell you that single-use doesn’t make sense for all patients. However, it makes sense for a certain population – for example patients who are immunocompromised. Imagine somebody who has a very high health risk if somehow cross infected with a germ that is transmitted during the procedure. For this patient do we go with a reusable cope or will we take a single-use scope? And that’s the doctor’s decision, but what we want to make sure as a provider/manufacturer that there is little difference in the choice of scope so the same quality of care can be provided to the patient. Because if you do it the other way around and you are a pure single-use provider you cannot offer this choice.
The PENTAX Medical Video Duodenoscopes ED32-i10 and ED34-i10T2 combine a sterile disposable elevator cap (DEC™) for single-patient use and simple disposal that advances cleaning capability of the duodenoscope to help reduce the risk of cross-contamination and improve patient care with High-Definition image quality for detailed endoscopic visualization during ERCP procedures.
Distal end of the PENTAX Medical Video Duodenoscope ED32-i10
TH: PENTAX Medical is leading the collaborative i-scan imaging processing project. Can you explain what this project is about and the purpose of it.
HH: “i-scan is one part of our general solutions approach. For i-scan there are different modalities which support doctors in each step of the diagnostic process. These i-scan modalities include SE – or Surface Enhancing mode – that improves detection, particularly of the shadowed parts of the lesion. There is TE – or Tone Enhancement – which helps in the characterization of the lesion by amplifying the colours so the doctors understand better what they are seeing and can make an informed medical decision. Then we have OE – or Optical Enhancement – an optical filter which helps in demarcation, to understand the actual size of the lesion in the macule that the doctor sees.
This is an example of how we support doctors each step of the way and that’s part of our solution-driven thinking. We are also involved with many physicians for the i-scan project all across Europe and some parts from the US. They add to the project by sharing their insights on how they can benefit from i-scan in their medical procedures. We also use this as part of our learning initiative. Whenever they have tricky images they have identified, they bring them to a forum where they can be discussed.
TH: PENTAX Medical has developed their own data management and software solutions for their medical imaging devices. Can you tell us more about these solutions?
HH: We are deprioritizing data management and hospital software solutions. We are now more focussed on a solutions approach by combining our products and services.
TH: PENTAX Medical’s latest image and video processor is the Optivista Plus. I understand it can also be used as an educational platform with its “TwinMode” setting. Can you tell us more about this device?
HH: The TwinMode is an interesting feature! As part of the educational setting, it is possible to show a previously recorded image on the screen so the doctor, or the students in training, can compare these images with the current ones they are seeing. So, for example with the i-scan project, images enhanced with one of the modalities can be compared to the same image without any enhancements. That’s how students learn when they can compare.
TH: What else is in the pipeline for PENTAX Medical?
HH: Our focus is set in the hygiene cosmos, where we have initiatives such as Power of Choice. We also have our World of Intelligence initiative that is focussed on the digital arena, like AI, which supports our solutions-driven approach. We ask the question, what kind of solution can we provide with our different products if you, the customer, combine them together. We have the processors and we have the scopes, we have the single-use scope, we have the semi disposable scopes, we have different image modalities which can be used in different combinations in order to provide the right solution for their particular case. So all that comes together with us being able to provide this choice for doctors.
The International Hospital Federation issues statement in support of Ukraine
, /in E-News, Editors' Picks /by panglobalThe IHF stands with hospitals during conflict, calls on members to provide support
The situation in Ukraine is a major concern for all of us, and the escalation of violence that has been reported on many different channels is alarming.
On 25 February, we released a message of solidarity with the people and the healthcare community in Ukraine.
The escalation of violence impacting hospitals and healthcare personnel is being reported by many authorities including:
Attacks on hospitals, healthcare workers, and ambulances are not acceptable. No matter the context. No matter the reasons. It is a violation of International Humanitarian Law, and we firmly stand against it.
Many international organizations and local actors are working hard, both inside Ukraine and in the neighbouring countries, such as Poland, Hungary, Slovakia, Moldova, and Romania to support refugees, mainly women and children. The UN Refugee Agency (UNHCR) has issued an alert that the number of refugees could reach 4 million rapidly.
IHF Members want to help, but the Ukrainians have limited logistical capacity to manage donations. We are recommending to the IHF community to get involved (either with financial or supplies support) through organizations acting in the field in neighbouring countries, or to the headquarters of these organizations. These trusted organizations have the capacity to redistribute the donations in a strategic manner.
Many organizations are providing emergency assistance in the region. The IHF would suggest supporting the following:
There are also initiatives that our members and partners have shared with us that we believe you will be interested to discover and support. For example:
Direct financial donations can be made via the PMM website.
If you are a healthcare professional who wants to volunteer, or if you want more information, you can contact Rafael Gotsens, International Medical Director, Teladoc Health, Inc. (rgotsens@teladochealth.com).
International study proposes stool analysis for early detection of pancreatic cancer
, /in E-News /by panglobalA genetic signature of 27 microorganisms in stool defines the high-risk population for pancreatic ductal adenocarcinoma, the most common pancreatic cancer, and could be used for early detection of the disease.
Núria Malats
Pancreatic cancer is not one of the most frequently diagnosed cancers, but it is one of the most lethal due to its early local extension and metastatic behaviour. Some of the reasons for this high fatality rate are late diagnosis of the disease, especially since symptoms are unspecific and appear rather late, and limited therapeutic options.
Using patient samples provided by a number of clinical collaborators, researchers from the Spanish National Cancer Research Centre (CNIO), led by Núria Malats, and the European Molecular Biology Laboratory (EMBL) in Heidelberg, led by Peer Bork, have found a molecular signature of 27 microorganisms in stool samples that could predict whether patients are at high risk of pancreatic ductal adenocarcinoma, the most common pancreatic cancer, and even diagnose patients with earlier stages of the disease.
A patent has been applied for to develop a pancreatic cancer diagnostic kit that detects these microbial genomes in stool samples in a rapid, non-invasive, and affordable way. The study was published in the journal Gut [1].
Detecting pancreatic cancer early
The symptoms of pancreatic cancer are silent and often appear in the late stages of the disease, when tumours usually cannot be removed through surgery. Therefore, there is an urgent need for non-invasive, specific, and affordable tests that are able to detect the disease early and improve patient survival.
“In many cases, once pancreatic cancer is detected, it is too late. We need to diagnose the disease at a much earlier stage, before symptoms appear. To do this, we need to identify and define the population at risk and have good screening tests to detect the cancer when it is still curable,” the researchers pointed out.
Recent data suggest that the microorganisms that coexist with cells in the human body – the microbiome – may play a role in the origin and development of pancreatic ductal adenocarcinoma.
To study this possible relationship in depth, the researchers conducted a unique case-control study with 136 individuals (57 newly diagnosed patients, 50 controls, and 27 patients with chronic pancreatitis) who were deeply characterized at epidemiological and clinical levels and from whom samples of saliva, faeces and pancreatic tissue were taken to analyse their microbiome. The subjects were recruited from two Spanish hospitals in Madrid (Ramon y Cajal Hospital) and Barcelona (Vall Hebron Hospital).
Most comprehensive study of the microbiome in pancreatic cancer
Contrary to common belief, the oral microbiome was not found to be associated with pancreatic cancer but faecal microbes were. “Sophisticated biostatistical and bioinformatics analyses have allowed us to construct a signature of 27 stool-derived microbes, mostly bacteria, that discriminates very well between cases with pancreatic cancer and controls, both in their most advanced and earliest stages,” said Malats and Bork. This gene signature was validated in an independent study carried out in two German centres, Frankfurt (Goethe University Hospital) and Erlangen (University Clinic Erlangen), and in 5792 faecal metagenomes from 25 studies in 18 countries. It is currently being studied in a Japanese population.
However, pancreatic cancer is a disease with a very complex aetiology and multiple risk factors such as age, obesity, diabetes, chronic pancreatitis, smoking, high alcohol consumption, blood type, and family history of cancer. To avoid biases and to ensure that the microbes identified are associated with pancreatic cancer and not with obesity, diabetes, or other risk factors, the authors controlled for these clinical and demographic variables in the analysis.
“This level of analysis is unprecedented in pancreatic cancer metagenome studies,” the investigators said.
As the researchers write in the pages of Gut, the high predictive value of this stool gene signature could serve as a biomarker to define the population at risk and, if validated in clinical trials, it could be used for early diagnosis of pancreatic cancer. “Currently, screening programmes are targeted to families with pancreatic cancer aggregation, which represent only 10% of the burden of the disease. The inclusion in these screening programmes of a stool analysis to identify the identified microbial signature could help to detect the rest of the population at risk,” they added.
The study
This research has been carried out in collaboration with the CNIO Epithelial Carcinogenesis Group led by Paco Real, the CNIO Molecular Cytogenetics Unit led by Sandra Rodríguez, the Ramón y Cajal University Hospital Oncological Department led by Alfredo Carrato, the Vall d’ Hebron University Hospital Digestive Disease Department with Xavier Molero, the Translational Hepatology Section in Goethe University Hospital led by Jonel Trebicka, and the group of Stephan Kersting in University Clinic Erlangen.
This study has been funded by the World Cancer Research, the European Research Council, the European Regional Development Fund, Spanish Ministry of Science and Innovation, the Carlos III Institute of Health, AESPANC-ACANPAN (Carmen Delgado and Miguel Pérez-Mateo grant) and the European Union (#018771-MOLDIAG-PACA, #259737-CANCERALIA).
Reference:
[1] Kartal E, Schmidt TSB, Molina-Montes E, et. al. A faecal microbiota signature with high specificity for pancreatic cancer. Gut. 8 March 2022.
https://doi.org/10.1136/gutjnl-2021-324755
What to know about prescribing cannabis medicines to patients with epilepsy
, /in E-News /by panglobalThere’s considerable interest in using cannabis-based medications to help treat drug resistant epilepsy, but clinicians have little guidance on how or when to prescribe these products. A working group comprised of paediatric and adult epilepsy specialists, clinical pharmacists, pharmacologists, and cannabis researchers from across Australia recently developed an interim “consensus advise” for prescribers and published it in the British Journal of Clinical Pharmacology [1].
The document provides an overview of the different cannabis medicines currently available for treating epilepsy in children and adults, with information on dose, drug interactions, toxicity, and type and frequency of symptom and seizure relief. The consensus advice will be updated as new evidence emerges and will provide the structure for a more definitive guideline in the future.
“In the absence of a registration dossier, scientific experiments and case reports are helpful to provide some guidance to optimized dosing. However, as in this guidance, observational data obtained from clinical practice, which often includes information not included in scientific experiments or even early clinical trial data, such as treating patients with other comorbidities, taking multiple medications, and patient diversity, can be very helpful to clinical practice,” said senior author Jennifer H. Martin, MBChB, MA, PhD, FRACP, a researchers at the University of Newcastle and the Director of the Australian Centre for Cannabis Clinical and Research Excellence.
The authors write: “Although interim, this consensus advice addresses much of the current practice gap by providing an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy in paediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure and frequency of symptom relief.”
Reference:
[1] John Lawson, Terry O’Brien, Myfanwy Graham, et. al. Expert advice for prescribing cannabis medicines for patients with epilepsy – drawn from the Australian clinical experience. British Journal of Clinical Pharmacology. 8 March 2022.
https://doi.org/10.1111/bcp.15262
Why public access to bleed control kits is essential
, /in E-News /by panglobalIn the United Kingdom there have been growing calls recently for increased access to publicly available bleed control kits. Easily accessible bleed control kits housed in public areas can provide a lifesaving tool and minimise the risks of critical injuries that can escalate into life-threatening catastrophic blood loss.
Increasingly, medical equipment and consumables are being developed for scenarios that could empower members of the public to take urgent action when responding to a range of common injuries and accidents, as well as criminal assaults.
The conversation around public access to bleed control kits is starting to gain traction globally, particularly for use in high population areas, such as shopping malls, arenas, and nightclubs.
Why public access to Bleed Control Kits is needed
Early medical intervention with a bleed control kit by a member of the public can make all the difference in saving a life if the injury is severe and there is the risk of significant blood loss.
In the UK, public access to Automated External Defibrillators (AEDs) is relatively commonplace, but access to lifesaving medical devices such as bleed control kits is only just starting to gain attention, with the first publicly accessible bleed control kit installed in Birmingham in November 2020.
Anthony Marsh, Chief Executive of West Midlands Ambulance Service, speaking to Birmingham Live, explained: “The average time it takes an ambulance crew to get to the scene is seven minutes. Catastrophic bleeding from a trauma injury such as a stabbing, shooting or road traffic collision can prove fatal in three to five minutes.”
“The bleed control kits can provide a few vital minutes until the ambulance arrives. If someone has access to one of these kits before a crew are able to arrive, they could potentially save a life.”
Bleed control kits can be housed with AEDs in public areas, in cabinets that alert emergency services when opened.
Bars, nightclubs and pubs are also becoming more aware of the need to provide emergency care in situations where alcohol becomes an aggravating factor.
What’s in a bleed control kit?
Bleed control kits contain lifesaving supplies, such as tourniquets, trauma wound dressing, examination gloves to prevent infection, scissors to remove clothing as well as chest seals and foil blankets. The kits also include essential information on how to use the kit. As with AEDs, some kits contain spoken instructions, while others contain visual instructions.
According to Reuters, research suggests that bleed control kit supplies should be stocked to support around 20 cases, which will cover minor injuries and more severe accidents that involve multiple people.
Why bleed control matters now
Small injuries involving cuts, scrapes and grazes will not require urgent treatment for bleeding, but bleed control becomes extremely important when an injury is severe.
In the UK, between September 2020 and September 2021 there were 46,239 knife or sharp instrument related offences recorded by police. While the aim is to reduce the number of stabbings, the reality is that venues need to be prepared for the worst case scenario.
The easy availability of life-saving resources, such as bleed control kits, are essential to provide medical assistance and treatment, particularly in the event of injuries that could result in catastrophic bleeding.
Bleed Control Kits in the public domain
According to a report in The Guardian, bleed control kits have been critical in helping the public respond to injuries as a result of assaults in the UK, including knife attacks. This has led to calls for the kits to be installed “in every village, town and city”.
In London, the City of London Police have helped to install over 320 bleed control kits in late night venues, and in other cities in the UK, police forces are providing the same kits to venues seen at risk.
For private companies, Aero Healthcare provides bleed control kits starting from £63.
Training is provided for free through various charity initiatives, including Control the Bleed.