Clinical pathology – Vet Clin Path Journal http://vetclinpathjournal.org/ Sun, 09 Jan 2022 19:19:37 +0000 en-US hourly 1 https://wordpress.org/?v=5.8 https://vetclinpathjournal.org/wp-content/uploads/2021/05/cropped-icon-32x32.png Clinical pathology – Vet Clin Path Journal http://vetclinpathjournal.org/ 32 32 Exagen Inc. and Queen Mary University of London Announce Exclusive License and Collaboration to Develop New Patented Molecular Signatures for Biologic Therapeutic Breeding in Rheumatoid Arthritis https://vetclinpathjournal.org/exagen-inc-and-queen-mary-university-of-london-announce-exclusive-license-and-collaboration-to-develop-new-patented-molecular-signatures-for-biologic-therapeutic-breeding-in-rheumatoid-arthritis/ Sun, 09 Jan 2022 17:00:00 +0000 https://vetclinpathjournal.org/exagen-inc-and-queen-mary-university-of-london-announce-exclusive-license-and-collaboration-to-develop-new-patented-molecular-signatures-for-biologic-therapeutic-breeding-in-rheumatoid-arthritis/

SAN DIEGO, January 09, 2022 (GLOBE NEWSWIRE) – Exagen Inc. (Nasdaq: XGN), a leading provider of autoimmune testing solutions, and Queen Mary University in London, today announced the signature of a research collaboration and an exclusive license agreement. The collaboration will focus on the development and optimization of patent-pending precision medicine approaches, based on RNA expression signatures, to personalize the selection of therapeutic agents for patients with rheumatoid arthritis. (PR). Both parties will contribute to the development of patent-pending tests, leading to the commercialization of new molecular tests that segment patients based on gene expression in their synovial tissue biopsies.

RA is estimated to affect approximately two million patients in the United States and is twice as common in women as in men and may be difficult to manage due to the variability in response to treatment of an patient to another. The selection of therapeutic agents for patients with RA remains a significant unmet need. Patients with RA often try several therapies empirically before finding one that decreases the activity of their disease. Placing a patient with RA on ineffective therapy risks advancing and aggravating the disease, further damaging the joints, and wasting a great deal of expense on expensive therapeutic agents. There is currently no reliable test to predict a positive patient response prior to the selection of commonly prescribed biological therapeutic agents.

Based on Professor Costantino Pitzalis and Dr Myles Lewis’s definition of molecular pathology of disease course and response to treatment, Exagen has acquired an exclusive worldwide license for a family of patent-pending tests relating to RNA expression models used in predicting patient response to prescribed csDMARDs and biologic therapies for RA. The tests use minimally invasive synovial tissue biopsies as input, which are then evaluated for RNA expression data. This data is then processed by proprietary algorithms that provide actionable information about the predicted csDMARD and the biological therapeutic response for patients with RA based on the RNA expression patterns of an individual patient.

Professor Pitzalis, Professor of Rheumatology in Arthritis and Deputy Director of the William Harvey Research Institute, Barts and the London School of Medicine and Dentistry at Queen Mary University in London, said: “I am delighted to be a part of this research collaboration with Exagen and I look forward to contributing to the development of diagnostics aimed at integrating molecular pathology into clinical algorithms to better define specific pathways leading to disease diversity in individual patients. This would better inform clinicians about patient prognosis and improve their ability to make informed decisions about prescribing drugs. Exagen’s track record in bringing diagnostics to market takes this opportunity to a whole new level, bringing the promise of precision medicine closer to clinical implementation.

Professor Pitzalis is a leading authority on rheumatoid arthritis. He leads a team of 50 clinical researchers and is the author of over 300 peer-reviewed publications in the field of inflammation, immunity and arthritis. Professor Pitzalis formulated this revolutionary approach to gene expression models with Dr Myles Lewis, head of the bioinformatics / biostatistics group at the Center for Experimental Medicine and Rheumatology. “We are delighted to be working with Professor Pitzalis and Dr Lewis of Queen Mary University in London to accelerate the development of their highly innovative RNA-based biomarker assays to better serve patients with RA. Professor Pitzalis is a well-respected thought leader in arthritis research, and Exagen looks forward to working with his group to deliver exciting and revolutionary products to improve the continuum of care for patients with the disease. rheumatoid arthritis, ”said Ron Rocca, President and CEO of Exagen Inc.“ Exagen is committed to developing and commercializing these tests to inform treatment decisions throughout the patient’s journey with RA. We intend to market the new tests under the name AVISE® RADR (Rheumatoid Arthritis Drug Response).

For more information on AVISE® RADR, please visit https://exagen.com/tests/avise-radr/.

About Exagen inc.

Exagen is dedicated to transforming the continuum of care for patients with debilitating and chronic autoimmune diseases by enabling rapid differential diagnosis and optimizing therapeutic intervention. Exagen has developed and markets a portfolio of innovative test products under its AVISE® brand, many of which are based on our proprietary Cell-Bound Complement Activation Products technology, or CB-CAPs. Exagen’s goal is to enable providers to improve patient care through the differential diagnosis, prognosis and monitoring of complex autoimmune and autoimmune diseases, including rheumatoid arthritis and lupus. For more information, please visit www.exagen.com.

About Queen Mary University of London and Queen Mary Innovation Ltd

Queen Mary University of London is a leading research intensive university with over 28,000 students representing over 160 nationalities.

A member of the prestigious Russell Group, we work in the humanities and social sciences, medicine and dentistry, as well as science and engineering, with inspiring teaching directly informed by our research.

In the most recent Research Excellence Framework, we were ranked 5th nationally for the proportion of research results that were world-class or internationally excellent. We offer more than 240 degree programs and our reputation for excellent teaching has been recognized with a silver medal in the 2017 Teaching Excellence Framework (TEF) awards.

Queen Mary Innovation Ltd (QMI) is Queen Mary’s wholly owned technology transfer company and is responsible for the commercialization and management of the University’s intellectual property and portfolio of spin-off companies. QMI protects and exploits the intellectual property derived from Queen Mary’s research and helps to maximize the economic and societal impact of this research. QMI Biopharma’s Associate Director of Marketing, Dr. Michele Hill-Perkins, led the negotiation and licensing transaction for QMUL.

For more information on QMI, please visit http://www.qminnovation.co.uk.

Forward-looking statements

Exagen cautions you that statements in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Exagen’s current beliefs and expectations. These forward-looking statements include, but are not limited to, statements regarding the expected benefits of collaboration with Queen Mary University, London and any potential development and commercialization of new patented molecular signatures for the diagnosis, prognosis and surveillance of diseases. autoimmune. The inclusion of forward-looking statements should not be taken as a representation by Exagen that any of its plans will be realized. Actual results may differ from those presented in this press release due to the risks and uncertainties inherent in Exagen’s business, including, without limitation: the development of new molecular signatures involves a long and complex process, and the collaboration may not lead to new patented molecular signatures or generate significant commercial test products in a timely manner, or not at all; the COVID-19 pandemic may continue to negatively affect our business, financial condition and results of operations, including our collaboration and development activities; risks associated with maintaining the collaboration and license agreement; and other risks described in previous Company press releases and documents filed by Exagen with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in Exagen’s annual report on Form 10-K and any subsequent filing with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Exagen makes no commitment to update such statements to reflect events that occur or circumstances that occur. exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Investor Relations
Exagen inc.
Ryan douglas
rdouglas@exagen.com
760.560.1525

Society
Exagen inc.
Kamal Adawi, Chief Financial Officer
kadawi@exagen.com
760.477.5514

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Slight pH Adjustment May Turn Metabolic Inhibitor Drug Into Promising COVID-19 Treatment https://vetclinpathjournal.org/slight-ph-adjustment-may-turn-metabolic-inhibitor-drug-into-promising-covid-19-treatment/ Sat, 08 Jan 2022 02:24:00 +0000 https://vetclinpathjournal.org/slight-ph-adjustment-may-turn-metabolic-inhibitor-drug-into-promising-covid-19-treatment/

Professor of Mechanical Engineering and Materials Science David Needham has shown that a slight increase in the pH of the solution might be enough to transform a metabolic inhibitor drug, traditionally used to treat intestinal parasites, into a promising prophylactic / preventative nasal spray and an early throat treatment spray for COVID-19[FEMININE[FEMININE

The results appear online December 28 in the journal Pharmaceutical research.

Since 1958, niclosamide has been used to treat parasitic intestinal infections in humans, pets and farm animals. Supplied as oral tablets, the drug kills parasites on contact by inhibiting their crucial metabolic pathway and cutting off their energy supply.

In recent years, however, researchers have tested the potential of niclosamide to treat a much wider range of diseases, such as many types of cancer, metabolic diseases, rheumatoid arthritis, and systemic sclerosis. Recent laboratory studies in cells have also shown that the drug is a potent antiviral drug, inhibiting a virus’s ability to cause disease by targeting the host cell’s energy supply that the virus co-opts for self-replication. .

Niclosamide acts primarily on the host cell’s mitochondria, which are like energy-producing batteries in the cell. The drug stops the cell from making its main energy molecule, adenosine 5′-triphosphate, or ATP. Without the energy supply to the infected cell, the virus finds it difficult to replicate viable copies of itself to cause other infections. These effects are reversible and do not cause cell death.

“Niclosamide lowers a cell’s energy dimmer and essentially blocks the virus,” said Needham, the sole author of the new study. When used in conjunction with vaccines, masking and other mitigation measures recommended for COVID prevention, the new niclosamide solution has potential as a backup strategy, he said. “This development could enable safe and effective nasal and pharyngeal sprays that provide additional protection behind the mask. “

Pivot in times of pandemic

In an ongoing collaboration with Will Eward, a surgical oncologist at Duke, Needham had previously shown that niclosamide has activity in bone cancer in mice and dogs when turned into a nanoparticle which, as he puts it, , “makes the medicine look like cancer food.” In another collaboration with Christina Barkauskas, assistant professor of medicine in pulmonary medicine at Duke, they were starting preliminary studies on the potential use of the same formulation of niclosamide for pulmonary fibrosis when the pandemic struck.

Like many researchers around the world, Needham has switched to studies led by COVID. After a Korean article examining the effectiveness of existing drugs against COVID-19 identified niclosamide as a potential target, it spent the following year researching a range of solution formulations, nanoparticles and microparticles. Korean studies in animal cells have shown that a low concentration of niclosamide is sufficient before infection to completely stop the replication of the SARS-COV-2 virus.

The animal cells used, however, are extremely tough and durable. To find out how effective and tolerable niclosamide might be for human use to fight COVID-19, Needham and Barkauskas turned to cells that were more relevant for the initial nasal and bronchial infection; respiratory epithelial cells; and hired other clinical researchers from Duke.

With no live virus to test with, the researchers focused on measuring the amount of niclosamide reducing ATP levels in cells of the human airways. Based on the ATP inhibition measurements against the virus from the Korean study, Patty Lee, professor of medicine, cell biology and pathology at Duke, and his postdoctoral fellow Sojin Kim, found that a few micromolar concentrations of the drug can lower ATP levels enough to potentially shut down virus reproduction completely without damaging the cells themselves.

These studies, however, were performed on cells submerged in cell culture media, which slows the rate at which niclosamide is absorbed and can act in cells. In other bench-top cell studies with Barkauskas and Zach Kelleher, a lab technician in his lab, researchers focused on cells in the human airways treated with only niclosamide buffered solution. Funded by a grant from the American Lung Association, the study suggests that even lower doses are enough to positively affect cells in the airways.

But these three studies do not take mucus into account.

The need for reformulation

Traditional allergy medications such as Flonase and Nasonex contain about 6000 to 30,000 times more of their respective active ingredients in solution than it would take to affect cells in laboratory studies. This is because only a small amount of the active drug passes the protective layer of mucus that constantly covers the back of people’s noses and throats.

Niclosamide, however, does not dissolve easily in water-based liquids that can be sprayed into a person’s nose and mouth. The normal attainable solution concentration of the drug at a nasal pH of about 6 or 7 is near or even lower than what laboratory studies suggest is necessary to prevent the virus from replicating in cells without protective mucus.

Based on calculations of how molecules like niclosamide diffuse through a thin layer of mucus, Needham estimates that a solution concentration about 10 times greater than that which can usually be achieved is required to produce a prophylactic spray and treatment function, and that it can pass through the mucus layer in milliseconds.

The question for Needham, then, was how to achieve this concentration.

PH adjustment

In the new article, Needham demonstrates that it is enough to increase the alkalinity of the solution to cross the mucous barrier and enter the cells where a COVID-19 infection first sets in. He found that raising the pH of the solution to a slightly alkaline pH of 8.0; acceptable for a nasal spray; can dissolve enough niclosamide to meet the requirements of its calculations. And increasing the pH to 9.2, which is still tolerable for a throat spray, beats that benchmark 10 times more and could be used early in the infection.

While promising, Needham notes, these results have yet to be tested in cells actually infected with COVID-19, as well as such cells protected by a layer of mucus, which requires finding partner laboratories and agencies with the resources. biocontainment and live viruses required.

A protocol for making liter-sized batches that can be filled and sealed into sterile-capped 10ml vials has already been developed in Duke’s Prep Pharmacy by Vincent Gaver, Clinical Research Pharmacist, and Beth McLendon. -Arvik, director of Investigational Drug Services. And in its new patent application, Needham also described a method for extracting niclosamide from commercially available tablets into solution without using organic solvents.

Because it acts on cells rather than the virus, niclosamide may work as a respiratory viral prophylactic agent, not only against COVID-19 and all of its variants, but also against any new virus. Although the vaccines are clearly effective, a nasal preventative would add additional protection. And even if an infection has already set in, this formulation could be used as an early treatment spray for the throat that could stop the viral load from making its way to the lungs, causing the disease’s most devastating effects. “

David Needham, study author

Needham has already applied for a patent and is actively seeking partners from industry, government and infectious disease institutes to help continue clinical trials and commercialization.

Source:

Journal reference:

Needham, D., (2021) The pH dependence of niclosamide solubility, dissolution, and morphology: motivation for potentially universal mucin-penetrating nasal and pharyngeal sprays for COVID19, its variants, and other viral infections. Pharmaceutical research. doi.org/10.1007/s11095-021-03112-x.

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Why some cases lead to rapid decline and death https://vetclinpathjournal.org/why-some-cases-lead-to-rapid-decline-and-death/ Thu, 06 Jan 2022 01:09:08 +0000 https://vetclinpathjournal.org/why-some-cases-lead-to-rapid-decline-and-death/ An international team led by Case Western Reserve University School of Medicine has made a significant breakthrough in understanding why Alzheimer’s disease progresses so rapidly in some people that they die within three years.

Researchers found link between misshapen and rapidly replicating strains of tau protein and accelerated cognitive decline – a critical finding that sheds light on variations in Alzheimer’s disease and may help lead to more accurate diagnoses and therapies targeted.

Such work could lead to changes in the management of Alzheimer’s disease, potentially offering patients and families a more precise prognosis.

“For the first time, we have established the link between the behavior of the tau protein in the test tube and the clinical duration of the disease in patients,” said Jiri Safar, professor in the departments of pathology, neurology and Case neuroscience. Western Reserve School of Medicine. “What the research generally says is that Alzheimer’s disease is not a single disease. There is a spectrum and different cases have distinct biological drivers of progression – and they should be treated as diseases. distinct. “

Their findings appeared on January 5 in Science Translational Medicine.

“We have to understand the disease and then categorize it into the different subsets or categories,” Safar said, “and that is indeed where we are now with Alzheimer’s disease.”

Safar’s co-authors include CWRU colleagues Alan Lerner, professor of neurology, and Mark Cohen, professor of pathology and neurology; David Westaway, professor in the Department of Medicine at the University of Alberta and director of its Center for Prions and Protein Folding Diseases; and Rohan de Silva, professor of molecular neuroscience at the Queen Square Institute of Neurology at University College London.

Safar hopes the research will help dispel the public perception that people with Alzheimer’s disease are likely to decline slowly over eight to ten years; 10 to 30% have the rapidly progressive form of the disease.

“We’re talking about 600,000 to 1.8 million patients in the United States alone,” he said. “So now we can think of it the same way we clinically treat malignant tumors like breast cancer or lung cancer – that different cancers have very different prognoses and treatment strategies.”

The next step is to translate the tools used in the study into clinical practice and identify those at high risk for rapid disease progression, then tailor treatments to the diagnosis.

Alzheimer’s disease research follows Safar’s groundbreaking work on prion proteins. He and his colleagues have found that when prions are folded incorrectly, they can replicate and damage the brain. They used concepts and tools developed in the prion work to study the mechanisms of misfolded proteins and applied them to the tau protein and Alzheimer’s disease.

Prion research has helped create a new paradigm for understanding Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases.

They knew that genetic and environmental factors linked to the increased risk of developing Alzheimer’s disease explained about 30% of cases. In recent research, they have sought to understand the remaining 70%.

The study

Scientists looked at brain samples from 40 people who died of Alzheimer’s disease – about half had slowly lost cognitive functions over the years and the rest declined rapidly and died within three years.

The researchers found that in the rapidly evolving cases, the nuclei of the tau protein particles had a different shape, meaning they had different structural organizations. Additionally, using processes they developed previously, they found that these misfolded tau species – like prions – can replicate faster in test tubes. They also deepened their understanding of the impacts of different structures and characteristics of abnormal tau and determined the attributes that predicted the rate of replication.

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Bendigo Health’s Coroanvirus Testing Site in McLaren Street Sees High Test Demand | Bendigo Advertiser https://vetclinpathjournal.org/bendigo-healths-coroanvirus-testing-site-in-mclaren-street-sees-high-test-demand-bendigo-advertiser/ Tue, 04 Jan 2022 01:31:00 +0000 https://vetclinpathjournal.org/bendigo-healths-coroanvirus-testing-site-in-mclaren-street-sees-high-test-demand-bendigo-advertiser/

coronavirus,

Bendigo Health reminds people to only queue for PCR tests if they have symptoms of COVID-19 or a positive rapid antigen test. McLaren Street testing clinic continues to experience high demand for COVID-19 testing. The strong demand comes as Victoria recorded more than 14,000 new cases of coronavirus on Tuesday morning, including 28 new cases for Greater Bendigo. A spokesperson for Bendigo Health said rapid antigen testing is the best test for people without symptoms who are in close contact. Read more: Increase in the number of heavy trucks expected on the roads during the harvest season “RATs are the appropriate test for people without symptoms who have been in contact with a person positive for COVID or for people who wish to undergo a precautionary test. As in other parts of Victoria, people tested for COVID-19 in Bendigo must wait up to five days for test results. Read more: Eaglehawk Elderly Care Facility Remains Locked After COVID-19 Case “Please be patient if you wait for a test, bring water and a hat and know if you don’t not meet the criteria for a PCR test, you will not be tested, “the spokesperson said. On Tuesday morning, the Victorian government announced that four private sector pathology clinics would suspend their services in an attempt to erase a history COVID-19 test results. Testing commander Jeroen Weimer said the four companies – 4Cyte, Australian Clinical Labs, Melbourne Pathology and Dorevitch – will close 54 sites later this week. Of these, 41 are 4Cyte “They’re disappointed to have to do this, but they’re doing something pragmatic to protect their own systems and to make sure that labs can get back on top of their workload,” Weimar said. You can consult the Current clinic wait times here: https://www.bendigohealth.org.au/page/3441 – with AAP Our reporters work hard to provide local and up-to-date news to the community. Here’s how you can access our trusted content:

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Stop dementia in the nose – nasal spray to treat, prevent Alzheimer’s disease https://vetclinpathjournal.org/stop-dementia-in-the-nose-nasal-spray-to-treat-prevent-alzheimers-disease/ Sat, 01 Jan 2022 20:28:05 +0000 https://vetclinpathjournal.org/stop-dementia-in-the-nose-nasal-spray-to-treat-prevent-alzheimers-disease/

Via repositioning the drug, Osaka City University creates a combination of rifampin and resveratrol and has shown in mouse models that nasal administration improves cognitive function without the negative liver side effects of rifampin only.

Via repositioning the drug, Osaka City University creates a combination of rifampin and resveratrol and has shown in mouse models that nasal administration improves cognitive function without the negative liver side effects of rifampin only.

Dementia is thought to occur when proteins called -amyloid, tau, and -synuclein build up in the brain and form oligomers. A research group from the Department of Translational Neuroscience at Osaka University Graduate School of Medicine had previously shown in a study using mice that the antibiotic rifampicin clears oligomers from the brain and improves cognitive function. However, the drug has been linked with side effects such as liver damage. Resveratrol, an antioxidant found naturally in plants, is used as a supplement in Europe and the United States. “To combat the negative side effects of the existing drug rifampicin, we thought about combining it with the hepatoprotective effects of resveratrol,” says Professor Takami Tomiyama, who acted as principal investigator for the present study.

Anti-dementia collunarium

The combination of the generic drug rifampicin and the food supplement resveratrol, and their intranasal administration with a nasal spray, would provide safer and more effective prophylaxis against dementia. Credit: Takami Tomiyama

This time, the research group administered a fixed-dose combination of rifampin and resveratrol intranasally five days a week for a total of four weeks to model mice from Alzheimer’s disease, frontotemporal dementia and Lewy body dementia, and observed their cognitive functions and brain pathology. The results showed that the combination significantly improved cognitive function in mice, inhibited the accumulation of oligomers, and restored levels of synaptophysin – presynaptic proteins that facilitate synapses. In addition, blood levels of liver enzymes, a marker for liver damage that normally increase with rifampicin, remained normal in the fixed dose combination. In addition, increased levels of expression of brain-derived neurotrophic factor (BDNF) were observed in the hippocampus, which was not observed with rifampicin alone. These results indicate that this fixed dose combination is superior to rifampicin alone in terms of safety and efficacy.

The results of this study have been published online in the Swiss scientific journal Frontiers in neuroscience December 13, 2021.

“The number of patients with dementia has increased all over the world, with some sources predicting the number of patients to double every 20 years. However, there is still no effective treatment for the disease, ”says Tomohiro Umeda, specially appointed speaker and first author of the study. “Recent studies have shown that abnormalities start to appear in the brains of patients with dementia more than 20 years before the onset of the disease. By investigating new therapeutic uses with existing drugs in a process called drug repositioning, the research team hopes to diagnose and prevent dementia before neurons start to die.

Additionally, based on the team’s previous research experience, nasal administration of a fixed-dose combination of rifampicin and resveratrol would increase drug transferability to the brain and further improve safety and medicinal effects. . The dosage used in this study was 0.02 mg rifampicin per mouse per day, or 1 mg / kg / day assuming a mouse weight of 20 g. “Converted to a human dosage based on body surface area, it becomes 0.081 mg / kg / day,” says Prof. Tomiyama, “currently rifampicin is prescribed at 10 mg / kg / day as an antibiotic, and in relation to that, confirmed to us an effect at a much lower dosage.

The development of a fixed-dose combination of rifampicin and resveratrol nasal spray is currently being led by Medilabo RFP, a high-risk company that emerged from the research team’s laboratory. Following the publication of this article, Medilabo RFP began preparations for global clinical trials. In November 2021, with the support of the Japan Foreign Trade Organization (JETRO), Medilabo RFP established a subsidiary in Massachusetts, United States.

Reference: “Oligomer-targeted prevention of neurodegenerative dementia by the intranasal combination of rifampicin and resveratrol – A preclinical study in model mice” by Tomohiro Umeda, Ayumi Sakai, Keiko Shigemori, Ayumi Yokota, Toru Kumagai and Takami Tomiyama, 13 December 2021, Frontiers in neuroscience.
DOI: 10.3389 / fnins.2021.763476

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Prostatectomy without biopsy is feasible, German study finds https://vetclinpathjournal.org/prostatectomy-without-biopsy-is-feasible-german-study-finds/ Wed, 29 Dec 2021 16:53:09 +0000 https://vetclinpathjournal.org/prostatectomy-without-biopsy-is-feasible-german-study-finds/

Radical prostatectomy after cancer confirmation via two advanced imaging techniques without biopsy is feasible, according to a retrospective study of 25 patients who refused biopsies.

“The results of our case series may trigger the discussion on [radical prostatectomy] without prior biopsy as a possible option in well-selected patients, ”write Valentin H. Meissner, MD, and colleagues at the Technical University of Munich, Germany.

Current guidelines call for a prostate biopsy if an elevated prostate specific antigen or abnormal digital rectal examination suggests cancer. But biopsies can lead to complications, such as sepsis, urinary retention, and hematuria requiring catheterization.

However, the use of multiparametric magnetic resonance imaging (mpMRI) alone may not be sufficient to diagnose patients. Studies show that pMRI misses about 10% of significant prostate cancers and has low positive predictive value.

In the current case series, the authors reported their experience combining two advanced imaging modalities – pMRI and prostate specific membrane antigen (PET) positron emission tomography (PSMA) – as the primary diagnostic tool. to detect and treat prostate cancer in patients who have refused biopsy.

“Improving the accuracy of prostate specific membrane antigen (PSMA) positron emission tomography (PET) scanning raises the question of whether this imaging modality can complement mpMRI to safely avoid biopsy. before radical prostatectomy, “Meissner and colleagues write in their review, published Dec. 6. in European urology.

Recent studies have already suggested that the two combined imaging techniques are more precise than mp MRI alone, suggesting that “men with suspicious results from PSMA-PET and mpMRI could potentially avoid the biopsy and undergo definitive treatment” , write the authors.

In the current case series, Meissner and colleagues followed 25 patients who elected to undergo radical prostatectomy based on the results of mpMRI and PSMA-PET imaging without biopsy, despite the surgeon’s recommendation to undergo a biopsy.

The men had a median PSA level at diagnosis of 7.3 ng / mL and a median age of 71 years. ) score of at least 4 and a PET score of at least 4 (with a median standardized absorption value [SUVmax] of 9.5).

After undergoing radical prostatectomy, all patients had significant prostate cancer greater than grade 1 on histopathological assessment, as defined using the International Society of Urological Pathology (ISUP). Specifically, eight of the 25 patients were ISUP grade 2, 15 were ISUP grade 3, and two were ISUP grade 5.

MpMRI and PSMA-PET had a sensitivity of 100% and a positive predictive value of 100%. PSMA-PET and mpMRI successfully identified four cases of seminal vesicle invasion, 4 of 6 cases of extracapsular extension, and 13 cases of locally contained disease. In four patients, researchers found lymph node invasion in the final pathology, and PSMA-PET correctly identified one of them preoperatively.

However, two patients whose cancer was suspected of extracapsular extension on mpMRI and PSMA-PET showed a disease locally confined to histopathology. Conversely, two patients with cancer suspected of a disease locally confined in these imaging studies showed extracapsular extension in histopathology.

The authors recognize “a risk of false positive results leading to unnecessary surgery”. But they argue that the risk could be minimized by experienced nuclear physicians using a validated SUVmax threshold.

“The results of the current retrospective case series were promising and showed that in patients with a strong suspicion of [prostate cancer] in mpMRI and PSMA-PET, avoidance of prostate biopsy before [radical prostatectomy] could represent a valid option in well advised and selected patients ”, write the authors.

However, they caution, “our case series is limited by retrospective design and small sample size. We want to make it clear that this practice should not be viewed as standard procedure at this time.”

As such, the authors requested a clinical trial with a larger patient population to validate the results.

Although Scott Eggener, MD, a urologist oncologist at the University of Chicago, Illinois, found the study stimulating and believes that a radical prostatectomy without a biopsy is worth considering, this option remains an academic question only at this stage. .

In Eggener’s experience, the only men who had radical prostatectomy without a biopsy sought prophylaxis because so many men in their families had died of prostate cancer.

But if enough men skip the biopsies, some will inevitably have surgery they didn’t need, he said. Medscape Medical News.

“It absolutely can fall in the trash of the history of prostate cancer. But if more studies are done thoughtfully, the combination of PSA, MRI and PET may someday help. ‘avoid biopsies for some men,’ said Eggener, who was not involved in the research.

A co-author, Matthias Eiber, reported consulting activities for Blue Earth Diagnostics, Progenics Pharmaceuticals, Keosys, Novartis, Telix Pharma, Amgen and Point Biopharma, as well as a patent application for rhPSMA. The other authors had nothing to disclose. Eggener did not report any relevant financial interest.

Eur Urol. Published online December 6, 2021. Summary

Laird Harrison writes on science, health and culture. His work has been published in magazines, newspapers, public radio and on websites. He is working on a novel on alternative realities in physics. Harrison teaches writing at Writers Grotto. Visit him on lairdharrison.com or follow him on Twitter: @LairdH.

For more news, follow Medscape on Facebook, Twitter, Instagram and YouTube.


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COVID-19 testing given priority at facilities in the local health district of West New South Wales | Daily Central West https://vetclinpathjournal.org/covid-19-testing-given-priority-at-facilities-in-the-local-health-district-of-west-new-south-wales-daily-central-west/ Tue, 28 Dec 2021 02:44:00 +0000 https://vetclinpathjournal.org/covid-19-testing-given-priority-at-facilities-in-the-local-health-district-of-west-new-south-wales-daily-central-west/

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Due to the high demand for COVID-19 testing and the resulting stress for New South Wales health pathology laboratories, the West New South Wales local health district has announced that it would prioritize testing at its facilities. From now on, inpatients in public hospitals and multi-purpose facilities, healthcare workers and elderly care facilities will be given priority. People with symptoms of COVID-19 will also be given priority treatment. People identified as close contacts of a confirmed COVID-19 case will be treated after these priority groups, and we urge patience if they have to wait after showing up for testing. COVID-19 testing for travel is not recommended at WNSWLHD facilities because due to the high demand for treatment, results are unlikely to be available within 72 hours. Any COVID-19 testing for travel will only be considered if capacity permits. This does not apply to clinics managed by external providers and turnaround times in clinics of these providers are also subject to demand. Anyone requiring a COVID-19 test to travel is advised to come to a clinic operated by an external provider such as Laverty Pathology, Histopath or Barratt & Forgeron. WNSWLHD cannot guarantee that results will be available within 72 hours if testing is performed by external providers. Testing is a strict priority to help reduce pressure on WNSWLHD facilities and NSW’s health pathology laboratories by limiting non-clinical or elective testing at these facilities. Our reporters work hard to provide local and up-to-date news to the community. Here’s how you can continue to access our trusted content: VOTE Send a letter to the editor using the form below

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Finding concentration in brotherhood https://vetclinpathjournal.org/finding-concentration-in-brotherhood/ Sun, 26 Dec 2021 11:02:36 +0000 https://vetclinpathjournal.org/finding-concentration-in-brotherhood/ Leslie S. Kersun, MD, MSCE, MSEd, discusses finding the right scholarship program; the challenge of balancing research, patient care and education as an intern; and find his center of interest during the fraternity.

Like many physicians, Leslie S. Kersun, MD, MSCE, MSEd, has known since childhood that she wanted to pursue a career in medicine. She found her calling in pediatric oncology as an undergraduate student at Dartmouth College in Hanover, New Hampshire, while volunteering with the child welfare department of a local hospital. The program provides developmental stimulation, support and advocacy for children’s emotional and psychological needs.

“I have met a lot of children with cancer because they were in the hospital a lot more often,” she said. “Then I noticed in medical school that I was really interested in cancer and blood disorders while we were doing these sections. Things all fit together over time. I didn’t have a lot of decisions to make; each step of the way fell into place.

She received her MD from Albany Medical College in New York and was a pediatric resident at Children’s Hospital of Philadelphia (CHOP) in Pennsylvania. She completed her first year of Pediatric Hematology / Oncology Fellowship at Children’s Regional Medical Center, now Seattle Children’s Hospital, Washington, and returned to CHOP to complete her training. During her training and early in her appointment to the faculty, she realized that she had a passion for medical education.

“As a scholar, I enjoyed teaching residents and medical students,” she said. “Shortly after completing my fellowship, I had the opportunity to help rotate residents in our oncology unit. It was my job to understand and adjust the way residents were educated when they attended their oncology internship.

Shortly thereafter, she became medical director of inpatients in oncology, in addition to becoming more involved in the scholarship program. She was later appointed Associate Director of Fellowships and is now Program Director for one of the largest pediatric hematology / oncology scholarship programs in the country. With the exception of her year in Seattle, Kersun has been with CHOP since 1996.

She recently assumed the role of Associate Designated Institutional Manager and, along with the Senior Medical Education Leadership Team, helps oversee more than 70 training programs at CHOP. Working at CHOP is fantastic, she says. “It’s a great place to work. There is a lot of expertise and dedication to education there. We have a great culture and there is always someone to help you with a patient or a question.

Kersun spoke with oncology fellows to discuss finding the right fellowship program; the challenge of balancing research, patient care and education as an intern; and find his center of interest during the fraternity.

Oncology fellows: You haven’t had a hard time finding your career path, but how do you help fellows focus when they enter the program?

Kersun: One of the most important things to consider when considering a scholarship program is the type of mentorship available to help you grow professionally. You need to think about the clinical mentoring structure of the program, as these faculty members will help you learn how to care for patients. Two of the three years of fellowship training focus on research. Depending on the type of research you are interested in, whether it is strictly laboratory research, more translational research, or clinically oriented research, you need to determine the type of mentors and resources available. This is essential when planning your career and determining who in this institution can help guide you down the path you want.

Then, of course, there are the life mentors. These may not be one of your assigned mentors for a particular area. They are teachers who have chosen a similar path, have structured their lives in a way that suits you, or have tips that can guide you.

What should residents look for in a scholarship program?

The scholarship is, for most, the last step in their training before moving on to a teaching position. It is essential to have mentors, resources and a program that can help you support your professional interests and a culture that allows you to thrive during training. These are very important questions to ask when considering applying for a program or going for a program interview; [it’s important] at [understand whether] this program can support your development and the areas of your career that are most important to you. It’s a little different from residency training. The interview process and the aspects that are most important to the program can be very different.

Typically, people who go for a scholarship are looking to get into academic medicine, but is the scholarship useful for people who want to become community physicians?

There is value in whatever you choose to do, so we don’t think doctors doing research in an academic center are more valuable than doctors who choose to have primarily clinical careers. Our scholarship will definitely train you for any career path that interests you. In pediatric oncology, there are far fewer opportunities in community medicine or private practice — that’s just not how most practices are structured. Children with cancer and blood disorders are most often seen in hospital settings because you need a blood bank; laboratory diagnostics; multiple specialties such as radiology, pathology, surgical specialties, radiation oncology; and various disciplines to better care for patients. It’s not that there aren’t community or private practices available; it’s just less common.

Some guy who comes to you in the middle of his third year and says, “Dr Kersun, I don’t know how to find a job. What do you tell them to take the next step to work as a doctor and researcher?

We talk to them about it from the start. Our division manager gives a talk on the job search process that is suitable for each intern. He explains how he can help read cover letters and contact potential employers to help our fellows find opportunities that will achieve their career goals. It also reviews what fellows should think about accomplishing during the training, and then how to choose a faculty position that will help them continue to advance their careers. Our research mentors and clinical mentors engage with fellows as they progress in shaping their interests and the opportunities that may be available to them.

Our program also has instructor positions, which serve as a transition period that lasts 1 to 3 years before obtaining a teaching position. This type of position is primarily intended for fellows who are interested in research. With only 2 years of scholarship dedicated to research, many interns did not have enough research experience to apply for a grant to support their salary upon completion of the training. They can use this transition time to further develop their projects and work with their mentors to move towards independence. They can also serve as attending physician during this period while further developing their research projects. When they have completed this period, they are ready to apply for a job.

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Top 5 Most Read Full Genomic Profiling Articles of 2021 https://vetclinpathjournal.org/top-5-most-read-full-genomic-profiling-articles-of-2021/ Wed, 22 Dec 2021 13:05:39 +0000 https://vetclinpathjournal.org/top-5-most-read-full-genomic-profiling-articles-of-2021/ The 5 most-read full genomic profiling articles of 2021 on AJMC.com mainly focused on the use of liquid biopsy and how biomarkers can offer providers new ways to help predict related outcomes. treatment and identify therapeutic targets.

In 2021, the 5 most-read full genomic profiling (CGP) articles of 2021 on AJMC.com primarily focused on the use of genomic profiling as a means of identifying possible treatment-related outcomes and targetable biomarkers. Two articles discussed how liquid biopsy can be used to improve providers’ ability to make treatment decisions for patients with non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC).

The year also brought news of Foundation Medicine’s partnership with Epic to streamline vendor decision-making capabilities by integrating CGP and other testing services in a central location.

5. Liquid biopsy of cerebrospinal fluid may improve therapeutic considerations in NSCLC

The researchers found that the unique genomic variations found in cerebrospinal fluid could be used as a fluid biopsy to safely and effectively improve the ability of providers to make decisions about treating patients with NSCLC with leptomeningeal metastasis. The results may represent a better surrogate endpoint for molecular analysis in patients with NSCLC whose tumor tissue is not available.

Read the entire article.

4. Study: Serial liquid biopsy may be useful to identify RAS Genetic mutations in mCRC

Serial liquid biopsies could serve as a useful tool to identify changes in the mutational state of genes in the RAS according to the results of the study. The retrospective analysis supported the notion that mCRC is an evolving condition and that mutational changes in RAS genes can be induced by antiangiogenic therapy in mCRC patients.

Read the entire article.

3. Study reveals biomarkers predictive of toxicity and efficacy of chemoradiation in NSCLC

Using CGP, several predictive biomarkers could be exploited to predict the efficacy and toxicity of chemoradiotherapy in patients with NSCLC, according to these September results. The results also showed that progression-free survival and overall survival were associated with some of the identified genes and that chemoradiation was limited by individual variations in radiosensitivity and the risk of radiation-induced chest toxicity.

Read the entire article.

2. Pathologists Discuss Mutations and Workable Tests in Metastatic Breast Cancer

Diagnostic tools and options for patients with recurrent or advanced metastatic breast cancer were presented at the National Comprehensive Cancer Network 2021 Virtual Congress: Biomarkers in Solid Tumors. Kimberly H Allison, MD, director of breast pathology at Stanford Cancer Institute (SCI), and Melinda L Telli, MD, director of the breast cancer program at SCI, used real-life examples to demonstrate how genetic profiling of these cancers could give rise to an actionable, targetable biomarker.

Read the entire article.

1. Foundation Medicine, Epic partner on access to genomic profiling in EHRs

Foundation Medicine has announced a partnership to integrate its CGP and other testing services with Epic’s electronic health record (EHR) system, which allows providers to electronically order genomic tests for patients within the Epic network. The optimized integration will support oncology practices, academic medical centers and other health systems by consolidating clinical and genetic information in a single location, enabling providers to make more streamlined clinical decisions.

Read the entire article.

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Australian Clinical Labs Continues To Raise Money From COVID Testing; again improves its orientations https://vetclinpathjournal.org/australian-clinical-labs-continues-to-raise-money-from-covid-testing-again-improves-its-orientations/ Tue, 21 Dec 2021 00:27:38 +0000 https://vetclinpathjournal.org/australian-clinical-labs-continues-to-raise-money-from-covid-testing-again-improves-its-orientations/

The arrival of omicron in Australia has led to a further increase in COVID testing volumes and Australian Clinical Laboratories (ASX: ACL) is one of the beneficiary companies.

This morning, the company improved its forecast for the first half of fiscal 22 for the second time in four months.

Once again, he credited the strong demand for COVID testing but also a positive performance from its non-COVID pathology business.

Previously, its revenues were between $ 437.5 million and $ 454 million, and profit between $ 86.3 million and $ 94.9 million.

But now he estimates revenue will be between $ 497.3 million and $ 517.2 million, and profit between $ 116.3 million and $ 128 million.

Australian Clinical Labs noted that NSW and Victoria were strong where the number of COVID-19 cases is higher in other states, but also where residents can travel between states once again but generally require COVID testing before. departure.

“We expect increased COVID-19 testing volumes to continue through the remainder of FY22 due to the impacts of new variants and outbreaks, the lifting of travel restrictions, and increased demand for commercial and travel testing. Said CEO Melinda McGrath.

However, Australian Clinical Labs did not provide guidance for the entire year, noting that COVID test numbers were often volatile.

The company’s shares are up 9% this morning and more than 35% since its IPO earlier this year.

Australian Clinical Labs Stock Price Table (ASX: ACL)

Other businesses benefiting from COVID testing

While Australian Clinical Labs recently passed the $ 1 billion market cap, it is still a minnow compared to Healius (ASX: HLS) and Sonic Healthcare (ASX: SHL) which are currently capitalized at $ 3.35 billion and $ 21.48 billion respectively.

Both companies, like Australian Clinical Labs, achieved outstanding results in FY21 using COVID testing as well as their other pathology departments.

Sonic was the most recent to provide a trading update, stating that revenue and profit for the first four months of FY22 was 5% and 16% higher, respectively, than in the previous corresponding period.

This followed a one-time profit for fiscal year 21, in which its net income grew 149% to $ 1.3 billion and revenue rose 28% to $ 8.8 billion.

Healius also recorded a one-time profit in FY21, recording pre-tax profit of $ 252.8 million, up 103% from the previous year.

And the two companies, along with Australian Clinical Labs, have recently been on the M&A trail with Healius buying Agilex Biolabs for $ 301.3 million and Sonic buying ProPath for an unspecified amount – both deals coming to light. last week.

A small cap stock benefiting from the COVID testing boom is Atomo diagnostic (ASX: AT1) which provides rapid tests.

Rapid tests have only been authorized by the TGA in recent months and Atomo is one such vendor. After selling less than 5,000 units in fiscal 21, it sold 100,000 units in the September quarter alone.

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