Vet Clin Path Journal Wed, 23 Nov 2022 15:49:04 +0000 en-US hourly 1 Vet Clin Path Journal 32 32 A multidisciplinary approach leads to a higher rate of completion of neoadjuvant treatment in pancreatic cancer Wed, 23 Nov 2022 15:05:45 +0000 Patients with localized pancreatic adenocarcinoma who received care in a multidisciplinary clinic had significantly higher neoadjuvant therapy completion rates than those treated in a specialty clinic.

Patients with localized pancreatic adenocarcinoma who received care at a multidisciplinary clinic had significantly higher neoadjuvant treatment completion rates than those treated at a specialty clinic, according to results of a retrospective study presented at Quality Care 2022 American Society of Clinical Oncology Symposium.1

Patients whose treatment was coordinated by a multidisciplinary clinic (n = 157) completed their neoadjuvant treatment regimen according to institutional standards at a rate of 71%, while the 83 treated in an individual clinic (surgical, medical or radiation). oncology) did so at a rate of 46.1% (P = 0.002). In addition, the enrollment rate in clinical trials was higher among the former (16.6%) than among the latter (7.2%) (P = 0.043).1

The adjusted odds ratio (aOR) for completion of neoadjuvant therapy by institutional standards for patients seen via multidisciplinary clinics versus standard oncology clinics was 3.35 (95% CI, 1.46- 7.07; P=0.004). In terms of clinical trial enrollment, the aOR in the multidisciplinary clinic cohort was 2.44 (95% CI, 0.94-6.35; P=0.067).1

Investigators used data from the Institutional Pancreatic Cancer Registry to compile a study population of patients diagnosed with localized pancreatic adenocarcinoma between 2018 and 2020 at Johns Hopkins Hospital in Baltimore, Maryland. To be eligible for the study, patients had to have a disease for which resection was ultimately undertaken and have come to Johns Hopkins either through its multidisciplinary pancreatic clinic or through one of its surgical, medical, or radiation clinics. oncology.

The primary outcome of the study was completion of neoadjuvant treatment according to stage-specific institutional standards. Clinical trial enrollment included only patients who had been admitted to an institutional clinical trial. The investigators noted that during the study period, it was standard practice for patients with resectable borderline disease to be treated with neoadjuvant chemotherapy for at least 4 months, with or without preoperative radiation therapy, before to explore. Patients with locally advanced disease received 4 to 6 months of chemotherapy, then radiotherapy, followed by possible exploration.

Baseline patient characteristics were well balanced across cohorts, with a median age of 67 years for those treated in standard clinics (range, 58-73 years) and multidisciplinary clinics (range, 61-73 years). The patients had a history of other cancers at a rate of 12% and 35.8%, respectively. Most patients in both arms had an ECOG performance status of 1 or less (63.9% versus 91.7%, respectively).

Additional findings showed that patients who came to Johns Hopkins through a multidisciplinary clinic experienced a survival advantage. Mortality rates were 28.7% in the standard clinic and 20.5% in the multidisciplinary clinic (P = 0.157).

More patients in the multidisciplinary clinic than patients in the standard clinic had neoadjuvant radiotherapy (59.7% versus 34.9%; P = 0.004). Patients in the standard clinical group had a slightly lower recurrence rate (38.5%) than those in the multidisciplinary clinical group (40.1%; P = 0.421).

The median number of visits to the multidisciplinary pancreatic clinic was 1 (range, 1-6) and the authors noted that multiple clinic visits were not associated with completion of neoadjuvant therapy.

Following the blueprint established by the Johns Hopkins Skip Viragh Center for Pancreatic Cancer Multidisciplinary Pancreatic Clinic, the team’s focus should combine the knowledge of medical and radiation oncologists, surgeons, radiologists, pathologists and other clinicians to provide a complete comprehensive review. The multidisciplinary clinic is also able to diagnose, educate and create personalized treatment plans for patients.2

Patients should meet with specialist clinicians based on their specific needs and then have their case reviewed by a panel of experts. The multidisciplinary clinic is best suited to patients with newly diagnosed and treatment-naïve disease, those with locally advanced unresectable or borderline disease, and those who have had surgery for a pancreatic cancer but who have not started chemotherapy and/or radiotherapy.

Study reveals new way to prepare imaging Wed, 23 Nov 2022 02:00:43 +0000

image: Dr. Benjamin Rotstein, Associate Professor in the Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa.
see After

Credit: Faculty of Medicine, University of Ottawa

Dr. Benjamin Rotstein and his collaborators unveil an operationally simple method for preparing carbon-labeled versions of drugs and diagnostics.

The development of new pharmaceuticals relies on the ability of scientists to elegantly design specific drugs for targeted clinical trials. And the isotopic labeling of drug candidates in research laboratories is crucial in this global effort.

In a new study, Laboratory of Dr. Benjamin Rotstein to University of Ottawa Faculty of Medicine collaborated with colleagues to unveil an operationally simple method for preparing carbon-labeled versions of drugs and diagnostics. They have developed a method to exchange a single amino acid atom – building blocks of proteins that are also used to make molecules – for its isotope.

“It’s really important in drug development because we want to know where the drug goes in the body, how it’s metabolized and eliminated so we can plan appropriate dosing and toxicity studies,” says Dr. Rotstein, associate professor at the Faculty of Medicine Department of Biochemistry, Microbiology and Immunology.

The work has been described in an article in natural chemistry, a high-impact journal that also published a separate article on the study in which two Danish scientists from Aarhus University described the team’s methods as “important for the field”.

Dr. Rotstein’s lab originally designed his experiments to function as a catalyst used by our bodies: pyridoxal phosphate, which removes carboxylic acid from amino acids and is the active form of vitamin B-6. But he says they wanted to make it work in reverse, and it turned out the mechanism was a little different from what they originally expected.

“We’re actually adding carbon dioxide and then removing the acid. So it’s a different mechanism that allows us to look at even better catalysts and expand the scope beyond amino acids,” he says.

The research was carried out in collaboration with colleagues from the University of Alberta and chemists from Sanofi, the French pharmaceutical company. Dr. Rotstein’s lab did the studies on carbon-11 and worked with these collaborators to uncover the mechanism of the reaction. His lab uses carbon-11 because it’s radioactive in a way that works well for medical imaging.

What are the next steps for his lab at the University of Ottawa? Dr. Rotstein and his team are currently studying how to make the reaction produce a single “mirror image” version of amino acids so that researchers don’t have to separate them after the fact.

He says they’re particularly excited about using amino acids at carbon 11 to measure how quickly our bodies produce protein, as it can be an indicator of disease.

“We also use them in imaging studies to learn more about metabolism and rates of protein synthesis in different tissues,” says Dr. Rotstein, who is also director of the Laboratory of Molecular Imaging and Radiochemistry Probes at the University of Ottawa Heart Institute.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of press releases posted on EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

The community supports Meowth | Wyndham Tue, 22 Nov 2022 00:29:14 +0000

By Fatima Hallum

A crowd gathered outside the University of Melbourne U-VET Werribee Animal Hospital on November 21 to protest its proposed closure.

The hospital provides specialized care and services for pets statewide.

U-Vet veterinary nurse Merissa Grovers said she had been at the hospital for nearly six years and was devastated to hear it might be closed.

“My heart is broken. For me, it’s not just my job,” she said.

“We are the only animal hospital in the West, our staff have nowhere to go, our customers have nowhere to go.”

Ms Grovers said the veterinary industry was already ‘drowning’ and if the planned closure took place she expected the shortage to worsen.

“The veterinary industry is often overlooked, but our pets are our family. Don’t we want the best for them?” she said.

“I really hope we can at least create some noise to show how important this is.”

Ms Grovers said she was “very overwhelmed” by the supportive response from the rest of the community.

“[The U-Vet hospital] is important to a lot of people,” she said.

A spokesperson for the University of Melbourne said the university encourages people to continue submitting feedback through the form linked to the U-Vet Facebook page.

“This is only a proposal, and we are actively consulting with the university community to ensure that the final decision has considered all potential options,” the spokesperson said.

“The proposal to cease operating U-Vet is in no way a reflection of the hard work and excellent service that our U-Vet staff provide to our customers and the community,” the spokesperson said. .

The university also offers the only globally accredited Doctor of Veterinary Medicine program in the state.

“If the proposal to cease operating the U-Vet Veterinary Hospital in Werribee goes ahead, alternative arrangements would be put in place to maintain necessary clinical teaching,” the spokesperson said.


Castle Biosciences Receives College of American Pathologists Accreditation for its Pittsburgh Clinical Laboratory Mon, 21 Nov 2022 12:32:06 +0000

FRIENDSWOOD, Texas–(BUSINESS WIRE)–Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced that the Board of accreditation from the College of American Pathologists (CAP) has accredited its clinical laboratory in Pittsburgh. This achievement follows a recent on-site inspection under the CPA’s Laboratory Accreditation Program.

“This important accreditation reflects Castle’s commitment to excellence, safety and quality, driven by our dedicated laboratory team,” said Kristen Oelschlager, COO of Castle Biosciences. “We are proud that clinicians and patients can use our innovative tests knowing that our clinical laboratories have received this accreditation reserved for laboratories operating to the high standards required by CAP.

CAP’s laboratory accreditation program was initiated in the early 1960s and is recognized by the US federal government as equal to or more stringent than its own inspection program. During the CAP accreditation process, inspectors review laboratory records and quality control procedures from the previous two years. CAP inspectors also review laboratory staff qualifications, equipment, facilities, safety program and records, and overall management. CAP accreditation is then granted to facilities that meet the highest quality standards for laboratory services. Once achieved, on-site inspections take place every two years to assess continued compliance with CAP accreditation program requirements.

Castle acquired its lab in Pittsburgh through the Cernostics, Inc. acquisition in December 2021, and subsequently launched ongoing process improvements and lab expansion efforts. With this accreditation, all of Castle’s laboratories are now CAP accredited, reflecting the company’s commitment to high quality standards and excellence in patient care.

About Castle Biosciences

Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company that improves health through innovative tests that guide patient care. The Company aims to transform disease management by putting people first: patients, clinicians, employees and investors.

Castle’s current portfolio includes tests for skin cancers, uveal melanoma, Barrett’s esophagus and mental health issues. Additionally, the Company has active research and development programs for testing in other diseases of high clinical need, including its test in development to predict systemic therapeutic response in patients with moderate to severe psoriasis, atopic dermatitis and related conditions. To learn more, visit and connect with us on LinkedIn, Facebook, Twitter and Instagram.

DecisionDx-Melanoma, DecisionDx-CMSeqDecisionDx-SCC, Melanoma MyPath, DiffDx-Melanoma, DecisionDx-UM, DecisionDx-PRAME, DecisionDx-UMSeqTissueCypher and IDgenetix are registered trademarks of Castle Biosciences, Inc.

About the College of American Pathologists

As the world’s largest organization of board-certified pathologists and a leading provider of laboratory accreditation programs and proficiency testing, the College of American Pathologists (CAP) serves patients, pathologists, and the public in promoting and advocating excellence in the practice of pathology and laboratory medicine. worldwide. For more information, read CAP’s annual report on

Forward-looking statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “sphere of security” created by these sections. These forward-looking statements include, but are not limited to, statements regarding: the ability of clinicians and patients to use our innovative tests knowing that our clinical laboratories have received CAP accreditation. The word “may” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain such identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those contained in the forward-looking statements, including, without limitation, our ability to maintain compliance with accreditation program requirements. CAP on an ongoing basis; and the risks set forth under “Risk Factors” in our Quarterly Report on Form 10-Q for the three months ended September 30, 2022, and in our other filings with the SEC. Forward-looking statements speak only as of the date they are made, and we undertake no obligation to update any forward-looking statements except as required by law.

Pentagon promotes critical race theory, gender identity ‘madness’: GOP report Mon, 21 Nov 2022 07:00:37 +0000

The Biden administration launched sweeping diversity and equity initiatives in the military that popularized elements of critical race and gender identity theory and significantly weakened the US armed forces, according to a report obtained exclusively by Fox News Digital.

“The singular purpose of our military is to ‘provide for the common defence’ of our nation,” the report said. “It cannot be turned into a leftist social experiment. It cannot be used as a cudgel against America itself. And it cannot be paralyzed by fear of offending the sensibilities of the teachers’ lounge from the Ivy League or progressive pundits.

“The world is a dangerous place, and the madness of the Biden administration is eroding our greatest source of security.”


The United States Marine Corps tweeted a picture for Pride Month with rainbow bullets.
(United States Marine Corps)

The report by Sen. Marco Rubio, R-Fla., and Rep. Chip Roy, R-Texas, details how the military has allocated resources to root out extremism in its ranks as it promotes predominantly left-leaning ideas about race and sex. This includes records of how military employees promoted critical race theory and embraced anti-white views.

For example, less than a month after his nomination by President Biden, Secretary of Defense Lloyd Austin asked commanders and supervisors at all levels to schedule a day to discuss extremism. But a Biden administration report, “Countering Extremist Activity Working Group,” later identified fewer than 100 instances of extremism among the 2.1 million active forces, a rate of 0.005%.

The report finds that instructors at military academies use “anti-racist” approaches to education that push soldiers to center their understanding of American society on acknowledging its racist past and present, according to the report. The Department of Defense, however, stressed that it does not teach critical race theory and focuses on intellectually challenging its military students and rooting out extremism.


Defense Secretary Lloyd Austin has come under fire from Republicans for pushing

Defense Secretary Lloyd Austin has come under fire from Republicans for pushing “woke” social experiments on members of the military.
(AP Photo/Susan Walsh)

Rubio said these race-based initiatives are a distraction and a danger to American security.

“Rather than standing up for American greatness and protecting our nation, the military is repeating woke nonsense,” Rubio told Fox News Digital. “It’s stupid, it doesn’t work and it’s dangerous. We need to spend more time thinking about how to counter Chinese aircraft carriers and less time thinking about pronouns.”

A few examples of “woke” defense policies have spread in the press. Kelisa Wing, head of diversity equity and inclusiveness at the Department of Defense, tweeted that she was “exhausted by these white people” and suggested that black people are incapable of racism, comments that have sparked an ongoing investigation at the agency. Bishop Garrison, another diversity officer at the agency, promoted elements of critical race theory through his praise of the 1619 Project, a controversial education project that depicts slavery at the heart of the story. American.

This emphasis on diversity, the Republicans’ report notes, extends even to the United States Special Operations Command, which oversees special operations conducted for national security. That group’s strategic diversity and inclusion plan, which all agencies were required to submit in response to an executive order from Biden, stated that “leaders must integrate diversity and inclusion efforts into corporate goals. unit, mission objectives, talent management initiatives and operational priorities for success”. Implementation.”


Republicans say the Pentagon avoided patriotic appeals to the military, which made recruiting more difficult.

Republicans say the Pentagon avoided patriotic appeals to the military, which made recruiting more difficult.

The report also notes that the military covers the costs of transgender procedures for its members and allows them to serve as transgender and use the restroom of their preferred sex. Military recruiting videos in recent years have touted the military’s inclusivity towards LGBT members with the use of the rainbow pride flag.

A US military base in Germany scheduled a drag queen story hour for children in its library this year, but canceled the event after facing backlash from the public.


Roy said this broad politicization of the military is a distraction from its focus on national security.

“The priority of the Department of Defense should be to train the men and women of our armed forces to be a united, lethal, combat-ready force, ready to defend the United States and its interests at all times” , Roy told Fox News Digital. “Instead, Biden’s woke Pentagon is using taxpayer dollars to promote blatant anti-American ideology.”

Kessler and BrainQ Join National Trial of Breakthrough Device to Improve Recovery After Stroke Sun, 20 Nov 2022 17:15:00 +0000

Researchers from the Kessler Foundation and the Kessler Institute for Rehabilitation (collectively “Kessler”) are enrolling participants in a nationwide trial of a breakthrough device to improve recovery after stroke. Kessler sites in West Orange and Saddle Brook, NJ, are among 20 sites across the United States participating in the EMAGINE Stroke Recovery trial, which combines therapeutic exercise with brain stimulation through an experimental wearable device . Steven Kirshblum, MD, is the principal investigator and Ghaith Androwis, PhD, is the co-principal investigator of the Kessler study.

Each year, strokes affect nearly 800,000 people in the United States, according to the Centers for Disease Control and Prevention. “Given the general impact of stroke on individuals, families and caregivers, as well as on health services and our economy, the benefits of improving stroke rehabilitation outcomes are substantial” noted Steven Kirshblum, MD, chief medical officer of the Kessler Foundation and Kessler Institute for Rehabilitation. Dr. Kirshblum is also chairman of the Department of Physical Medicine and Rehabilitation at Rutgers New Jersey Medical School.

“Too often, stroke results in long-term disability that negatively affects quality of life,” Dr. Kirshblum continued. “We now know that with early and intensive intervention, stroke survivors have the ability to regain function. The EMAGINE trial capitalizes on this neuroplasticity of the brain and spinal cord by augmenting standard rehabilitation with stimulation electromagnetic therapy and making the therapy available in different settings, including the home,” he explained.

Each site plans to enroll people within four to 21 days of moderate to severe ischemic stroke. At Kessler, three participants to date have been enrolled in the study, which is randomized, simulation-controlled and double-blind, according to Dr. Androwis, principal investigator at the Mobility and Rehabilitation Engineering Research Center of the Kessler Foundation and director of the Center’s Robotics and Rehabilitation Research Laboratory.

The first participant completed the nine-week protocol, which includes 45 one-hour sessions administered five times per week. During each session, the participant performs therapeutic exercises while wearing the device, which fits over their head and torso without interrupting the participant’s ability to perform functional tasks with their upper limbs.

“Given the promising results of our already completed BrainQ trial in people with chronic spinal cord injury, we are excited to investigate the potential benefits of this non-invasive brain and spine stimulation intervention in people disabled by stroke,” said Dr. Androwis.

Using machine learning, the BQ device targets affected areas of the brain with electromagnetic field therapy. The therapy, which is low intensity and regulated frequency, is administered with the current standard of physiotherapy and occupational therapy, with the aim of facilitating neurological recovery. Preliminary findings were promising, prompting the FDA to award Breakthrough Device designation to BrainQ’s device in 2021.

BrainQ’s developers see the device’s potential for a flexible therapy continuum, from acute care to rehabilitation and post-discharge for home use. “Being able to stay engaged in therapy throughout the recovery process is a unique aspect of the EMAGINE study,”

pointed out Dr. Androwis. “Participants can access this experimental therapy from home, under the supervision of a trained caregiver and remote monitoring by a member of the study team.”

We are delighted to have true leaders in rehabilitation research and clinical care, including the Kessler Foundation and the Kessler Institute, as our partners in the EMAGINE trial. Together, we are striving to achieve our common goal: to transform the future of stroke rehabilitation by restoring lost mobility through innovative technology applied to home solutions.”

Yotam Drechsler, CEO of BrainQ

Eligible participants are recruited from the Kessler Institute for Rehabilitation, a Select Medical inpatient rehabilitation hospital that provides rehabilitative care for stroke and other disabling conditions. The Kessler study team assesses the eligibility of patients hospitalized for stroke rehabilitation.

The study is funded by BrainQ, developer of the experimental device.

Northern Ireland protocol will block 51% of veterinary medicines in seven weeks – vets are giving a serious public health, food supply, animal welfare and trade warning, a leading vet has warned . Sat, 19 Nov 2022 19:55:39 +0000

Now, Dr. Esther Skelly Smith, junior vice-president of the North of Ireland Veterinary Association and the British Veterinary Association NI Region, says the grace period on protocol restrictions on bringing veterinary pharmaceuticals into NI should run out at the end of December.

An estimated 51% of all current veterinary drugs will be blocked from January 1, she said.

A leading veterinary association has warned that a blockage of Northern Ireland’s protocol on importing 51% of animal medicines from Britain after January 1 could have serious implications for salmonella and eggs in Northern Ireland. Esther Skelly-Smith says there are serious ramifications for public health and the broader agri-food economy.

“The mood is, we’re very worried,” she told the News Letter.

“This will affect all sectors – farm, equine and companion animals – and will have significant implications for animal health and welfare, public health, trade and agricultural economics. The drugs affected include anesthetics and vaccines, including the salmonella vaccine for poultry, the loss of which poses a significant public health concern.”

“But it will not only affect agriculture, it will also affect pets and the equine industry. And the botulism vaccines that we can currently order from South Africa, these require an import license special and we’re afraid we won’t be allowed once the grace period ends.”

The loss of salmonella vaccines “could potentially mean that we won’t have certain egg products or eggs available due to public health concerns” and certain food products “could become more expensive” as a result, she warned.

Dr Esther Skelly-Smith warns the protocol will block 51% of veterinary drugs from Britain in seven weeks – with potentially serious public health ramifications, for example with salmonella.

“Our choice of veterinary medicines will be limited. So we could have welfare issues for your dog and your cat if we cannot use the veterinary medicine we want. This has a big implication on welfare.”

The NI protocol means that each batch of freshly manufactured veterinary medicinal product destined for the NI will need to be specially tested to confirm that it meets EU requirements.

“Longer term, the scale and costs of the changes needed to implement EU drug requirements mean that companies are likely to pull products from the NI market because it is too small for a viable commercial solution can be found.

The lack of Salmonella vaccines for poultry could also mean that NI products could be excluded from certain markets, for example the EU.

And even if a solution is found immediately, some veterinary suppliers have to buy the drugs well in advance.

“There doesn’t seem to be a will between the UK and the EU to deal with this issue, even though they are aware of it. That’s why my associations have been raising this issue for a considerable amount of time.”

“We want the government and the EU to agree on an extension of the grace period to mitigate the immediate effects. And in the long term, we would like them to come up with a solution to allow veterinary drugs to flow freely, similar to agreed for medicinal products for human use. medicinal products.”

The News Letter invited comments from the EU and the Irish government in response to Dr Skelly Smith and UFU President David Brown.

The UK government responded: “The UK’s priority is to protect the Belfast (Good Friday) Agreement, and our aim has been and always will be to preserve political stability in Northern Ireland.

“We are currently in talks with the EU to resolve the issues with the protocol. Our proposals would ensure that veterinary medicines are available across the UK at the same time as in the EU.”

The spokesman added that the UK’s preference has always been for a negotiated solution over protocol, but also said it was needed quickly, which is why he introduced the Protocol Bill. Northern Ireland in parliament.

An EU spokesman said he would not comment on Dr Skelly-Smith’s concerns.

He added: “The EU is engaging constructively with the UK to find common solutions regarding the implementation of the protocol. In this context, the Commission is ready to find a solution with the United Kingdom to ensure the long-term continuity of the supply of veterinary medicinal products to Northern Ireland.

“The Commission has already shown flexibility in the field of veterinary medicinal products. In an opinion published in December 2021, it gave companies more time to adapt. The Commission will keep the timetable set out in this opinion under review. .”

Meanwhile, UUP Agriculture spokesman Tom Elliott also sounded the alarm about it.

“The potential impact on our agribusiness industry is significant to say the least and it should never have happened,” he said on Friday. “We have an unrivaled agribusiness industry, with excellent markets in Britain, the EU and around the world, which contribute over £500million to the economy of Northern Ireland.

“This is a very significant issue, not only for animal health and welfare, but also for public health, the food supply chain and the farming community in Northern Ireland. potential for serious repercussions. The risks are very real and should be treated as a matter.” urgently and that is why I have written to Her Majesty’s Government to point out this inequality and ask them to do everything in their power to resolve this problem.

Meanwhile, DUP South Down MP Diane Forsythe met Taoiseach Micheál Martin during her visit to her constituency on Friday morning.

“As the only Unionist MP for South Down, it was a useful opportunity to impress on Micheál Martin the need to replace protocol,” she said. “No elected union representative from South Down supports the protocol. We operate power sharing, not majority rule.

International committee proposes MS progression framework guided by pathophysiological mechanisms, not clinical phenotype Fri, 18 Nov 2022 23:33:05 +0000

For years, multiple sclerosis (MS) has been defined by 3 clinical courses: relapsing-remitting, primary progressive and secondary progressive. Now, however, a recently published article by the International Advisory Committee on Clinical Trials in Multiple Sclerosis suggests that MS patients share qualitatively similar disease characteristics regardless of clinical course, and that the progression of disability is neither dichotomous nor genetically determined, which ultimately implies the need for a new framework for viewing disease.1

The article was authored by Tanja Kuhlmann, MD, associate professor in the Institute of Neuropathology at the University Hospital of Münster and part-time adjunct professor in the Department of Neurology and Neurosurgery at McGill University, and her colleagues. It offers a major first step towards eliminating the phenomenological classification of MS. Notably, Kuhlmann et al recognized that until the underlying mechanisms of the disease are better clarified, any new view of the course of MS will be flexible, and the adoption of biology-based definitions will present challenges. operational challenges, “as existing descriptors are deeply integrated into clinical research and healthcare systems” as well as regulatory processes.

“The goal is to move away from purely clinical descriptions of discrete phases, such as relapsing or progressive MS, and to understand MS as an ongoing process driven by mechanisms of nervous system damage counterbalanced by reserve and repair” , co-author Tim Coetzee, PhD, head of advocacy, services and science at the National MS Society, said NeurologyLive®. “Any new MS classification framework will require a step change in how all stakeholders understand and describe the disease. This will take several years and international collaborative efforts, but it would allow development and endorsement of approaches more biological treatment options for each individual with MME.”

The article focused on clarifying the 1996 and 2013 clinical course descriptors, commonly referred to as the Lublin-Reingold classification, with the aim of determining an approach to developing a new framework for describing disease. Overall, the idea is that disease progression towards progressive disease reflects a partial shift from acute, mostly localized injury to generalized inflammation and neurodegeneration, coupled with the failure of compensatory mechanisms such as neuroplasticity and remyelination.

A previously published study has shown that the existence of an ongoing intrathecal immune response is usually manifested at the time of diagnosis by the presence of central nervous system-specific oligoclonal bands.2 In the acute phase of the disease, activation of microglia and macrophage and lymphocyte infiltrates accompanies demyelination and plaque formation; however, these inflammatory mechanisms do not disappear in approximately 20% of lesions. Non-resolving inflammation not only leads to injury, but can also prevent repair, the study researchers noted.

Kuhlmann et al noted: “An open and critical question is whether inflammation must resolve before tissue repair can begin. The development of sensitive and specific non-invasive imaging markers that detect non-resolving inflammation , such as paramagnetic rim sign, future development of robust [cerebrospinal fluid] and blood biomarkers of the same processes, could answer this question.”1

Inflammation has also been closely linked to axonal and neuronal damage in MS patients. Although it remains a challenge to measure the cellular, molecular and metabolic mechanisms of neuroaxonal damage, the resulting global and regional brain atrophy – detectable early in the course of the disease – has been associated with an increased risk progressive accumulation of disability.3 Progression of long-term disability independent of relapse activity, also known as silent progression, is also correlated with accelerated brain atrophy. The international committee noted that, consistent with this thinking, several phase 2 trials including patients with progressive MS have begun to use induced atrophy as primary outcome measures.

Oxidative stress and mitochondrial dysfunction, another major topic discussed in the article, have been shown to contribute to glial and neuronal damage, loss of axonal energy, and loss of neural network function. Additionally, high levels of oxidative stress can induce damage to axons, neurons, dendrites, and oligodendroglia in MS lesions.4 Mitochondria, usually disrupted in MS, move from the cell soma to the demyelinated axon after demyelination; however, the peak of this potentially beneficial mitochondrial response is only reached after the onset of axonal degeneration.5

“Energy breakdown can practically be assayed in vivo using magnetic resonance spectroscopy, but a combination of laboratory and imaging techniques that can reliably assess ongoing oxidative injury and mitochondrial dysfunction in the lesions is necessary,” wrote Kuhlmann et al.1 “Thus, evidence for associations between molecular mechanisms of injury and progression of multiple sclerosis comes primarily from small proof-of-concept studies, and standardization of methods will be needed for implementation in clinical trials and the practice.”

Aging is another important factor that plays a role in the progression of MS. In adults, older age at diagnosis is associated with more rapid accumulation of ambulatory disability, which is currently a defining feature of progressive MS, and greater impairment. Telomere attrition length, a prototypical biomarker of aging, was associated with greater disability in cross-sectional and longitudinal analyses, independent of disease duration and chronological age.6

Reproductive aging can also affect the progression of MS. While women are at increased risk of developing MS, men with MS may have earlier and more rapid development of disability. Although not fully understood, several studies have suggested that the progressive pathology and disability of MS is accelerated during the period of Additionally, the loss of sex-specific steroid production could explain the phenomenon of women with MS appearing to catch up with men in terms of disability in later decades of life, the study authors noted.

Looking ahead, the researchers concluded that “consistent with current trends across medicine, we envision a future in which clinical benefits flow directly from biomarker-based, biology-driven treatment decisions,” noting that in addition to the ongoing modifications this new framework will require, “comprehensive patient education efforts will also be required. As such, the development of a roadmap for the implementation of any new framework will be a key future focus of the International Advisory Committee on Clinical Trials in Multiple Sclerosis.”1

1. Kuhlmann T, Moccia M, Coetzee T, et al. Progression of multiple sclerosis: time for a new mechanism-based framework. Neurol lancet. Published online November 18, 2022. doi:
2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions to the McDonald criteria. Neurol Lancet.2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2
3. Chard DT, Alahmadi AAS, Audoin B, et al. Mind the gap: from neurons to networks to outcomes in multiple sclerosis. Nat Rev Neurol.2021;17(3):173-184. doi:10.1038/s41582-020-00439-8
4. Lassmann H, van Horssen J. Oxidative stress and its impact on neurons and glia in multiple sclerosis lesions. Biochim Biophys Acta.2016;1862(3):506-510. doi:10.1016/j.bbadis.2015.09.018
5. Licht-Mayer S, Campbell GR, Canizares M, et al. Enhanced axonal response of mitochondria to demyelination provides neuroprotection: implications for multiple sclerosis. Acta Neuropathol.2020;140(2):143-167. doi:10.1007/s00401-020-02179-x
6. Krysko KM, Henry RG, Cree BAC, et al. Telomere length is associated with disability progression in multiple sclerosis. Anne Neurol. 2019;86(5):671-682: doi:10.1002/ana.25592
7. Kalincik T, Vivek V, Jokubaitis V, et al. Sex as a determinant of the incidence of relapses and the progressive course of multiple sclerosis.Brain 2013;136(part 12):3609-3617. doi:10.1093/brain/awt28
Jerry Radke Obituary – The Des Moines Register Fri, 18 Nov 2022 19:25:19 +0000

Jerry Keith Radke, 84, of Nevada, Iowa passed away peacefully in heaven on November 1, 2022 at 6:30 p.m. from complications of a recurrent brain meningioma. He was surrounded by his loving family at Accura Healthcare, Ames, Iowa. Jerry was born in Ripon, Wisconsin on April 11, 1938, to Edward Ludwig and Vera Ione (Phillips) Radke, the eldest of four boys. Jerry grew up on the family farm, working with his grandparents’ dairy cattle, beef cattle, pigs, chickens, ducks and geese. The family grew corn, alfalfa, oats, barley, peas, tame hay and marsh hay. His father put him on a tractor when he was three years old. Jerry recounted how his feet touched the pedals as he leaned his head against the tractor seat! Jerry also talked about helping his grandmother quilt. He was, indeed, a Renaissance man. He attended Henderson School, a one-room school, until 8th grade. It was the boys’ job to walk to the nearest farm to get a bucket of water from the farmer’s dairy and pour it into the school tank for the drinking fountain. Jerry said one of the few times he was reprimanded by the professor was when he dipped a young woman’s braid in the ink well. His grandfather and father had also attended this school. He attended Ripon High School and during summers worked for Green Giant as a crop control inspector, checking crops and testing for moisture to determine if they were ready for harvest. He participated in Cub Scouts, Boy Scouts, football, track, 4-H and Future Farmers of America. Jerry retained his primary and secondary school report cards, which recorded excellent academics and a strong work ethic. Jerry was an accomplished musician, playing organ, piano and accordion. Jerry, 12, played the accordion and his brother Mike, 10, played drums at weekends and birthday parties in Ripon. At age 15, Jerry began giving accordion lessons. When Jerry was 16 and Mike was 14, their band, “The Rhythmaires”, featured Jerry on accordion, Mike on double bass, with a trumpet player and drummer. They have performed for parties, weddings, proms, after proms and at the exclusive Green Lake Country Club. In college, he taught accordion and piano lessons to help pay for his room and board. Later, Jerry’s accordion skills would always bring joy to his mother-in-law, Violet Charlson. His father, Otto Book, had played the accordion at many family gatherings. Jerry’s music reminded him of those special family times. Jerry earned a Bachelor of Science in Soils from the University of Wisconsin – Madison. During this time, he participated in the Army Reserve Officer Training Corps program. While commissioned, 1st Lt. Radke served with the U.S. Army Signal Corps at Fort Monmouth, New Jersey as an electronics instructor. Jerry received his Master of Science in Soil Physics from Iowa State University, Ames, Iowa. He returned to the University of Wisconsin, Madison, to earn his doctorate in soil physics. During his 35-year career as a soil physicist, Jerry worked at the North Central Soil Conservation Research Lab, Morris, Minnesota. He was also Assistant Assistant/Associate Professor, Soils, University of Minnesota, studying soil structure, soil temperature, and instrumentation automation. Jerry took a sabbatical at the Waite Agricultural Research Institute, University of Adelaide, Glen Osmond, South Australia. He was also an Associate Professor, Sols, at Pennsylvania State University when he worked at the Central Weather Station, conducted field studies, modeling, and electronic communications at the Rodale Research Center (Rodale Institute) in Kutztown, Pennsylvania. Jerry retired from the United States Department of Agriculture, Agricultural Research Service, National Soil Tilth Lab, Ames, Iowa. At this time, he was also a Collaborative Associate Professor of Agronomy at Iowa State University, teaching meteorological instrumentation. He has published research articles on soil freezing and thawing, including the effect of water and nutrient movement in soil profiles, which is necessary to develop improved management strategies. Additional research trips included Cali, Colombia, and St. Petersburg, Russia. Scientists from several countries have requested copies of his research publications over the years. Jerry was a member of the American Society of Agronomy, Soil Science Society of America, American Meteorological Society, and Soil Conservation Society of America. He served as Story County Soil and Water Conservation District Commissioner from 2000-2013 and Deputy Commissioner from 2013-2022. Jerry joined the Morris Lions Club in 1965 and transferred to the Nevada Lions Club when he moved to Iowa. He has held several positions with this service organization, most recently as webmaster for the Nevada Lions Club. Jerry married Barbara Thorndike, also of Ripon, Wisconsin, on August 4, 1962. They had three children, Greg, Earl and Katrina. They have taken their children on numerous camping trips across the United States and Canada to help them develop a love for adventure and nature. Jerry had been a member of the church since his youth, was baptized and confirmed to Grace Lutheran in Ripon. After moving to Nevada, he joined the Memorial Lutheran Church, serving on several committees. On June 4, 1994, Jerry married Susan (Charlson-McLain) at Memorial, where they had met while serving on the Outreach and Fellowship Committee. Their blended family includes Greg and Anne Radke, their children Chloe and Phoebe; Earl and Monica Radke, their children: Mackenzie Machovec, Nolan and Heather Machovec, their children Levi and Elyanah, Mason Machovec and his children Ethan and Marshall, and Kennadie Machovec; Katrina (Radke) and Ross Gerry and their children Brenner, Benjie, Shanti and Sanjay; Steve Pannkuk and Alicia Quella, their children Zach, Sam and Josh; Emily (McLain) and Sanjay Negi, their children Lenore and Imelda; Christina (McLain) and Joe Larson, their children Austin, Jenna and Tyler and Frank McLain, V. Jerry brought her family laughter, joy, love and many travel memories. He had a great sense of humor and could be a little mischievous. He served his church and community selflessly. Jerry is survived by his wife of 28 years, Susan and their blended family, his brothers Michael (Linda), Rodney (Jeannie) and Brian (Pam) Radke, numerous nieces, nephews and extended family. A celebration of Jerry’s life will be held November 19 at 11:00 a.m., Memorial Lutheran Church, 701 11th Street, Nevada, Iowa. A lunch and a time of remembrance will follow the service. A private family interment will be held at Madison Township Cemetery, Forest City, Iowa at a later date. In lieu of flowers, donations may be sent to Memorial Lutheran Church, Nevada Lions Club or the Watersheds and Wildlife Program (Prairie Rivers of Iowa),

Posted on November 18, 2022

Posted in the Des Moines Register

Lab-grown red blood cells used for mini-transfusion by Cambridge researchers in trial that could transform treatments Fri, 18 Nov 2022 07:45:00 +0000

Two people have been transfused with lab-grown red blood cells in a first global trial involving Cambridge researchers.

If proven safe and effective, engineered red blood cells could revolutionize treatments for patients with blood disorders such as sickle cell disease and those with rare blood types, for which it is difficult to find suitable matches.

Chief investigator Professor Cedric Ghevaert, professor of transfusion medicine and consultant haematologist at the University of Cambridge and NHS Blood and Transplant, said: ‘We hope our lab-grown red blood cells will last longer than those from of blood donors. If our trial, the first of its kind in the world, is successful, it will mean that patients who currently need regular long-term blood transfusions will need fewer transfusions in the future, helping to transform their care.

red blood cells

The manufactured blood cells were grown from donor stem cells and transfused into volunteers in the RESTORE randomized controlled clinical trial, which involves a number of partners.

Professor Ashley Toye, Professor of Cell Biology at the University of Bristol and Director of the NIHR Blood and Transplant Unit in Red Blood Cell Products, said: “This challenging and exciting trial is a huge stepping stone for manufacturing blood from stem cells. This is the first time that lab grown blood from an allogeneic donor has been transfused and we are excited to see how well the cells are performing at the end of the clinical trial.

When patients receive a standard donation, they receive red blood cells of different ages. But the lab-grown cells are all fresh, so they should work better and potentially last longer, which would mean fewer transfusions for patients who regularly need blood. This would reduce the risk of iron overload due to frequent transfusions, which can lead to serious complications.

Although the trial is a step towards the future availability of laboratory-grown red blood cells as a clinical product, for the foreseeable future engineered cells can only be used for a very small number of patients with very complex needs, which means that blood donations remain of crucial importance.

Co-lead researcher Dr Rebecca Cardigan, NHS Blood and Transplant Component Development Lead and Affiliate Lecturer at the University of Cambridge, said: ‘It’s really fantastic that we are now able to grow enough medical grade red blood cells to allow this trial to begin. We are really looking forward to seeing the results and knowing if they work better than standard red blood cells.

No adverse effects have yet been reported in the two healthy volunteers involved in the NIHR BioResource who received laboratory-grown red blood cells. The amount of lab-grown cells infused into the assay ranges from approximately 5ml to 10ml – one to two teaspoons.

To grow them, the stem cells were separated from blood donated to the trial and then used to grow red blood cells in a laboratory at the NHS Blood and Transplant Advanced Therapies Unit in Bristol.

At least 10 participants will receive two mini-transfusions at least four months apart, one of donated standard red blood cells and the other of lab-grown red blood cells, to find out if young red blood cells made in the lab last longer than the cells made in the body.

Further trials will be necessary before any clinical use.

John James, chief executive of the Sickle Cell Society, said: “This research offers real hope for difficult-to-transfuse sickle cell patients who have developed antibodies against most donor blood types. However, it should not be forgotten that the NHS still needs 250 blood donations every day to treat people with sickle cell disease and this figure is increasing. The need for normal blood donations to provide the vast majority of blood transfusions will remain. We strongly encourage people of African and Caribbean descent to continue to register as blood donors and begin donating blood regularly.

Dr Farrukh Shah, Medical Director of Transfusion for NHS Blood and Transplant, said: “Patients who need regular or intermittent blood transfusions may develop antibodies against minor blood groups, making it more difficult to find blood. donor that can be transfused without the risk of a life-threatening reaction. This world-class research lays the foundation for making red blood cells that can be safely used to transfuse people with conditions like sickle cell disease. The need for normal blood donations to provide the vast majority of blood will remain. But the potential of this work to benefit difficult-to-transfuse patients is very significant.

The trial is a joint research initiative of NHS Blood and Transplant and the University of Bristol, in collaboration with the University of Cambridge, Guy’s and St Thomas’ NHS Foundation Trust, the NIHR Cambridge Clinical Research Facility and the Cambridge University Hospitals NHS Foundation Trust. It is partially funded by a grant from the National Institute for Health and Care Research (NIHR).