Clinical pathology – Vet Clin Path Journal Mon, 21 Nov 2022 15:48:53 +0000 en-US hourly 1 Clinical pathology – Vet Clin Path Journal 32 32 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.

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
How does autism affect the brain? Study finds changes in ASD Wed, 16 Nov 2022 19:39:24 +0000

November 16, 2022

The brains of people with autism experience widespread molecular changes in the cerebral cortex. The most differential changes occur in the primary visual cortex, according to a recent study published in Nature which analyzed 11 cortical areas of the brain.1 Most molecular profiling studies show changes limited to the frontal and temporal cortex.

To better understand the brain pathology of autism spectrum disorders (ASD), the researchers performed RNA sequencing analysis on 112 post-mortem samples. Consistent transcriptomic signatures of TSA were found in all cortical regions analyzed in the study. The largest expression signal came from the primary visual cortex (BA17).

Compared to control samples, ASD brains demonstrated significantly reduced gene expression between regions of the cerebral cortex. The primary visual cortex and parietal cortex (BA39/40), which function as primary sensory regions, showed significant patterns of attenuation. These results suggest that cortical regions are more molecularly homogeneous in people with autism and pronounced in the posterior region of the brain.

“It is interesting to speculate that the substantial changes seen in primary sensory regions may be related to the generalized sensory processing differences in ASDs, which are so prevalent that they have been included in the DSM-5 diagnostic criteria,” the researchers wrote.

An attenuation in regional transcriptomic identity (ARI) results in a “reduced magnitude of gene expression” and was often used as a marker in the present study. By clustering up- and down-regulated ARI genes into co-expression modules, researchers identified consistent dysregulation that spanned cortical association regions in ASD samples. Neural changes (GeneM9), astrocyte reactivity (GeneM32) and disruption of the blood-brain barrier (GeneM24) were found to extend beyond the frontotemporal regions. Genetic risk variants of ASD (GeneM5 and IsoformM37) have also been identified.

“The results presented here significantly refine our understanding of the molecular pathology of ASDs beyond the previously established ‘down-regulated neuron’ and ‘up-regulated glia/immune’ functional categories seen in the frontal and temporal lobes.”

Of the 112 postmortem specimens, 49 were individuals with idiopathic ASD and 54 were neurotypically matched controls. A total of 725 brain samples were used. A diagnosis of ASD was confirmed using the Revised Autism Diagnostic Interview or based on clinical history. Samples were collected through the Harvard Brain Bank as part of the Autism Network Project, in addition to the University of Maryland brain banks.

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Folbigg’s life and advances in genetic research Sun, 13 Nov 2022 19:10:00 +0000

New South Wales will conduct a second inquiry into Kathleen Folbigg’s convictions. At the center of this new investigation is new data on the protein calmodulin – specifically one of its coding genes, CALM2 – and a mutated form of the gene known as G114R, which can cause heart arrhythmias in young children.

In this timeline, Cosmos compares the story of the Folbigg affair to advances in scientific understanding of the human genome; how genes code for functional proteins; and research on CALM2which will be presented to the survey.



Alfred Hershey and Martha Chase demonstrate that DNA contains genetic information, not proteins.



Hodgkin and Keynes suggest that there may be receptors in cells that move calcium, based on previous experience – in hindsight, this role can now be attributed to the protein calmodulin.

June 14, 1967


Kathleen Megan Donovan – later Folbigg – was born in Sydney.



Marshall W. Nirenberg, Har Gobind Khorana, and Robert W. Holley win the Nobel Prize in Medicine for their interpretation of the genetic code and its function in protein synthesis.

January 8, 1969


Folbigg’s mother murdered by her father.



The hypothetical Hodgkin and Keynes receptor is attributed to the calmodulin protein. At this point, genetic sequencing did not exist and so protein analysis did not shed light on genomics.



Frederick Danger develops a technique to sequence DNA – this is then used to sequence the first human genome.



James Gisella and his team find the location of a gene responsible for Huntington’s disease.



Kathleen marries Craig Folbigg.

February 20, 1989


Caleb Folbigg dies aged 19 days.



It aims to fully sequence the first human genome with a 15-year timeline.

February 13, 1991


Patrick Folbigg dies at the age of 8 months.



A technique is being developed to genetically test embryos for diseases such as haemophilia while they are still in the womb.

August 30, 1993


Sarah Folbigg dies at the age of 10 months.



Several studies refine the molecular function of the calmodulin protein gene family. Calmodulin is found to be a multifunctional protein that binds calcium to help regulate, among other things, the cell cycle and cell division. Like the characterization of genes, the function of a gene in the body does not illuminate the clinical relevance of the gene and protein.



The CALM2 gene is characterized – that is, the gene has been compared to others in its family to estimate small nucleotide differences. Gene characterization only infers related genes and does not show the function of the gene or the clinical consequences of mutations it contains.



The first fully sequenced human chromosome is published by the Human Genome Project.

March 1, 1999


Laura Folbigg dies at the age of 18 months.



The first draft of the human genome is published by the Human Genome Project, at a cost of US$300 million.



Human genome project completed with 99.99% accuracy. He reports about 20,000 to 25,000 human protein-coding genes.

October 24, 2003


Folbigg sentenced to 40 years in prison for murder; the period of unconditional release is 30 years, then reduced on appeal to 25 years.



Improvements in sequencing technology increase genome sequencing time by 70 times.



Launch of the 1000 Genomes project, with the aim of sequencing a large cohort of genomes. Next-generation sequencing dramatically reduces the cost of genome sequencing to US$16 million.



Study shoes that mutations in CALM1, a close relative gene of CALM2, can lead to sudden cardiac arrest. The subject of this study was a 23-year-old woman who suffered sudden cardiac arrest at the age of four, but was resuscitated. From there, many studies find correlations between CALM gene mutations and cardiac arrest.



Another study shows that calmodulin mutations are associated with multiple cardiac arrests in infants.



Newly identified mutations in CALM2 are linked to susceptibility to congenital arrhythmia – a genetically inherited irregular heartbeat or rhythm.



The cost of sequencing a complete human genome draft drops to less than US$1,500 and takes 4-12 weeks.

June 10, 2015


New South Wales Governor David Hurley receives a petition to review Folbigg’s convictions. The motion raises a reasonable possibility of his innocence based on forensic findings.



The 100K Genomes project is completing the sequencing of 100,000 genomes for patients with rare diseases or cancer.

October 20, 2018


NSW Conviction Inquiry opens.

March 2019


Inquest hearings are held and the genomes of Folbigg’s children are sequenced.

May 2019


The Calmodulin Registry reports that two American children have died from the mutation present in the Folbigg girls, Sarah and Laura.

July 2019


The investigating commissioner finds no reasonable doubt about Folbigg’s beliefs. Functional validation of the Folbigg mutation could not be completed before the end of the investigation.

November 2020


A research team led by Stephen Kingsmore from the Rady Children’s Institute for Genomic Medicine in San Diego (USA) estimates that infant mortality from genetic diseases is between 10 and 21%, but treatment guidelines only covered 70% diseases. They suggest that genomic sequencing of infants could help reduce mortality.


A paper, “Infanticide vs. hereditary cardiac arrhythmias”, is published, showing that the mutant variant of CALM2, G114R, was present in both Folbigg children. The authors also report that both male children had mutations in the BSN gene, associated with severe epilepsy in young mice and neurodegenerative disease in adulthood.

March 3, 2021


Petition for Kathleen Folbigg’s pardon presented to NSW Governor Margaret Beazley.

May 18, 2022


Beazley orders an investigation into Folbigg’s convictions.

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Prepare, transform, improve: digital transformation in the NHS | HSJ Partners Fri, 11 Nov 2022 06:27:26 +0000

How, where and when patient care is delivered is changing.

Sponsored by

There is a natural evolution towards smart health services, where technology is integrated into clinical pathways and the digital patient is the new normal. It is essential that our health services, staff and NHS patients are ready for this. Because ultimately, smarter healthcare means more efficient and safer patient care.

Healthcare organizations at any stage of their smart healthcare journey need a strong technology procurement strategy that establishes close collaboration between their procurement and ICT functions.

They will also need to optimize their resources through their purchases, adhering to clear integrated care system requirements and cost improvement programs, while keeping social value and net zero carbon programs in mind.

At Crown Commercial Service, the UK’s largest public procurement organization and an executive agency of the Cabinet Office, we’ve put together a step-by-step guide to buying digital transformation solutions in the NHS. We explore the three main phases, with a clear breakdown of program stages and projects along the way.

Picture 1

Year 1 – Preparation

The first step is to develop the technology strategy that aligns with your NHS trust’s organizational development plan and its intended outcomes. From there, you can develop your program, create your design and delivery structure, prepare outlines and full business cases, and allocate budgets.

Next, you will need to review your existing assets with the goal of getting the maximum value from what you already have. Where do you need to refresh your core infrastructure and networks? How can unified communications bring together phone, email, and instant messaging to complement each other and foster collaboration? You will also need to think about how your devices, applications and databases will be deployed and managed, and how cybersecurity requirements can be met across all aspects of the IT estate.

Years 2 and 3 – Transform

Take the example of digitizing patient records. These can be integrated into clinical software and systems, facilitating the digital delivery and receipt of patient data at the point of care. If you need to digitize historical paper documents, consider the other processes and resources needed. You will need a validation process to verify that scanned documents match the original paper versions and create new workflows to ensure they are securely available.

Smart technologies can also be deployed to enable patient engagement and empowerment throughout their clinical journey. You can integrate systems such as image archiving and communication, radiology, pathology, pharmacy and bedside monitoring, focusing on interconnecting and sharing data, using standards messaging systems such as Health Level Seven. Review your data warehouse and how a central data store could improve your reporting and analytics; you also need to build integration into your solutions, considering how you can safely extend use to other organizations such as primary, acute, mental health and social services.

Years 4 and 5 – Improve

The human element cannot be lost in any digital transformation process. Smart champions involved in the implementation stage of your training program will be able to take greater ownership of the process. Training providers can create tailored training programs that empower users and tackle resistance to change. Real-time data and intuitive dashboards can inform your decision-making, provide more accurate clinical coding, and improve analysis of current and future activity. You might even want to think about how apps could help improve the patient experience and facilitate access to clinical services.

At this point, you should aim to put the digital patient at the heart of everything you do. You can prescribe digital solutions to the most vulnerable and disadvantaged, but make sure all health services are inclusive and think about how you can help patients learn the basic digital skills they will need to access services autonomously – and support those who can’t. Focus on early intervention and prevention initiatives with your fellow integrated care system providers.

Learn more

CCS has developed a free, easy-to-use guide to digital transformation in the NHS. Learn more and download the guide from the CCS website.

DOJ Steps Up Review of EHR Vendor Agreements: What the ModMed Settlement Means for the Life Sciences Industry | King and Spalding Tue, 08 Nov 2022 23:33:58 +0000

On November 1, 2022, Modernizing Medicine, Inc. (“ModMed”), an electronic health record (“EHR”) technology provider, entered into a settlement agreement with the Department of Justice (“DOJ”), agreeing to pay $45 million to resolve allegations that he caused the submission of false claims in violation of the False Claims Act (“FCA”) in part by soliciting and receiving bribes from a pathology.1 The settlement represents the fourth resolution from the U.S. Attorney’s Office for the District of Vermont that focuses on EHR technology, underscoring the office’s commitment to investigating agreements around the development and use of EHR systems. The DOJ and other state and federal agencies recognize the growing role that EHRs play in the delivery of healthcare and, therefore, are focusing more on how life science companies could use them to promote their improperly produced. The growing scrutiny of EHR technology underscores the importance of closely reviewing agreements with EHR vendors to mitigate potential risks.

The settlement agreement. The settlement stems from a who tam lawsuit filed by the former vice president of product management at ModMed. The complaint alleged that ModMed violated the Anti-Kickback Act (“AKS”) and the FCA through three of its marketing programs. First, the DOJ alleged that ModMed solicited and received bribes from Miraca Life Sciences Inc. (“Miraca”) in exchange for recommending and arranging for ModMed users to use the services of Miraca pathology laboratory. Specifically, the complaint refers to a strategic marketing agreement between ModMed and Miraca, as set out in a draft letter of intent (“LOI”), in which the two companies “tried to make the partnership mutually beneficial and to allow Miraca and ModMed to share success and…tried to ensure the strategic and financial alignment of the two organizations.2 The draft letter of intent cited in the complaint also refers to “co-marketing/promotion” which includes recognizing Miraca and ModMed as partners, issuing joint press releases and co-developing marketing materials. .

Second, the DOJ alleged that ModMed conspired with Miraca to improperly give ModMed’s EHR platform to healthcare providers (“HCP”) in an attempt to increase lab orders to Miraca and simultaneously add clients to ModMed’s user base. In particular, the complaint notes the alleged exchange of sales leads and data between Miraca and ModMed that detail vendor behavior to target new customers for either or both companies and to maximize both companies’ return on investment through donations from Miraca’s EHR platform.

Third, the DOJ alleged that ModMed bribed current HCP customers and other influential healthcare industry sources to recommend ModMed’s EHR platform and refer potential customers to ModMed. The complaint notes that in internal emails, ModMed employees openly acknowledged that the referral program was intended to drive sales. Further, the complaint alleges that ModMed’s compensation to certain influential sources was tied to the volume of business generated, as opposed to any fair market value for marketing activities.

Collectively, the allegations illustrate the increased scrutiny of EHR platforms by the DOJ and highlight that these vendors are subject to many of the same compliance risks as life sciences companies. The allegations also show how scrutiny of these tech companies can draw attention to their business partners, including pharmaceutical and medical device companies, who are often attractive targets for whistleblowers and government authorities. of law enforcement. Notably, Miraca paid $63.5 million to settle its own separate allegations that it violated the FCA by offering subsidies to healthcare professionals for EHR systems and free or discounted technology consulting services. .3

Implications for the life sciences industry. The ModMed settlement represents an emerging trend in enforcement that focuses on life sciences companies’ agreements with companies that offer point-of-care technologies used by healthcare professionals, such as of EHRs, which could influence the items or services that healthcare professionals prescribe. EHRs and similar technologies have been a staple for many years, and we are now starting to see application priorities catching up with the technology. The ModMed settlement notably follows the January 2020 Practice Fusion settlement which involved relationships between an EHR (Practice Fusion) provider and pharmaceutical manufacturers. Practice Fusion would have allowed pharmaceutical companies to participate in the design of clinical decision support alerts, including selecting the guidelines used to develop the alerts, defining the criteria that would determine when a healthcare professional would receive an alert and, in some cases, even the redaction of the language used in the alert itself. This settlement also involved allegations of Practice Fusion’s inappropriate focus on commercial interest and return on investment for manufacturers.4

Life sciences companies should carefully consider their relationships and agreements with EHR vendors and similar technology platforms that facilitate or could influence clinical decision-making. Relationships that might be perceived as improperly focused on commercial interests, rather than providing accurate and truthful education and information to EHR users, are particularly sensitive. Discussions and communications regarding the potential return on investment or business benefit for the parties to the arrangement will attract attention. Law enforcement authorities are also particularly skeptical of commercial messages inserted into EHRs when there is no transparency as to who sponsored the message, especially when a third party could benefit. commercially of the message (such as a manufacturer or a laboratory). Additionally, life science companies should be aware of the marketing practices of technology vendors with whom they have agreements. Suppliers’ communications and agreements with their customers could bring unwanted attention to suppliers and, therefore, to their agreements with life sciences companies.

1See ModMed Settlement Agreement (November 1, 2022), available at:

2See ModMed Complaint (November 1, 2022), available at:

3See DOJ press release (January 30, 2019), available at:

4See DOJ press release (January 27, 2020), available at -0.] ]]> Levels of macrophage migration inhibitory factors are associated with disease activity and possible complications of membranous nephropathy Thu, 03 Nov 2022 10:15:53 +0000

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    Trastuzumab plus FOLFOX for HER2-positive bile duct cancer refractory to gemcitabine and cisplatin: a phase 2 multi-institutional trial from the Korean Cancer Study Group (KCSG-HB19–14) Mon, 31 Oct 2022 23:48:50 +0000


    Overexpression or amplification of HER2, which is present in 15% of all cases of bile duct cancer, has been identified as a molecular drug target by genomic profiling. In the Phase 3 ABC-06 trial, the folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen showed a survival advantage over active symptom control as a treatment for second line of cancer of the bile ducts. Our objective was to evaluate the clinical activity of FOLFOX plus trastuzumab, an anti-HER2 antibody, as a second- or third-line treatment for HER2-positive bile duct cancer.


    This study was an open-label, non-randomized, single-arm, multi-institutional, investigator-initiated Phase 2 trial in participants 19 years of age or older with HER2-positive (defined as immunohistochemistry 3+ or immunohistochemistry 2+ and positive in situ hybridization or ERBB2 gene copy number ≥6 0 by next-generation sequencing) bile duct cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) that progressed on chemotherapy containing gemcitabine and cisplatin (with one or two lines previous authorized chemotherapy). During the first cycle, patients received trastuzumab-pkrb intravenously at 6 mg/kg on day 1, and FOLFOX (compound oxaliplatin intravenously [85 mg/m2]intravenous leucovorin [200 mg/m2]and fluorouracil [400 mg/m2 bolus] every day 1, and fluorouracil [2400 mg/m2 infusion] on days 1-2. During the second cycle, participants received trastuzumab-pkrb intravenously at 4 mg/kg and FOLFOX every 2 weeks until unacceptable toxic effects or disease progression. The primary endpoint of the study was objective response rate based on RECIST version 1.1, assessed in participants who completed at least one study cycle. The response rate threshold for a positive objective response rate was 25%. This trial is registered with (NCT04722133) and is ongoing.


    34 participants were enrolled between June 26, 2020 and September 1, 2021. At the time of data cutoff on May 1, 2022, the median follow-up was 13 0 months (IQR 11 0–16 9), with three participants remaining on treatment. Ten patients had a partial response and 17 had stable disease; the overall response rate was 29.4% (95% CI 16.7–46.3) and the disease control rate was 79.4% (95% CI 62.9–89, 9). The median progression-free survival was 5.1 months (95% CI 3.6–6.7); median overall survival was 10·7 (95% CI 7·9–not achieved). The most common grade 3 or 4 treatment-related adverse events were neutropenia (ten
    [29%] 3rd and 9th year participants [26%] grade 4), grade 3 anemia (five
    [15%] participants), and grade 3 peripheral sensory neuropathy (four [12%] attendees). There were no cardiac toxic effects or treatment-related deaths. The global health assessment score (EuroQoL-VAS) did not change significantly throughout treatment. Symptoms of sensory and motor neuropathy, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Chemotherapy-Induced Peripheral Neuropathy Questionnaire, did not change from significantly over time.


    For HER2-positive bile duct cancer, the second- or third-line biosimilar trastuzumab plus FOLFOX showed promising activity with acceptable toxicity, warranting further investigation.


    Boryung Pharmaceutical, Celltrion, National Research Foundation of Korea, National R&D Program for Cancer Control through the National Cancer Center, Yonsei University College of Medicine.

    A new approach to TMS may slow cognitive decline in Alzheimer’s disease Wed, 26 Oct 2022 21:00:34 +0000

    A new approach to repetitive transcranial magnetic stimulation (rTMS) that targets the precuneus appears to slow the progression of cognitive and functional decline in patients with Alzheimer’s disease (AD), according to new research.

    Results from a 6-month phase 2 double-blind randomized trial show that patients with Alzheimer’s disease who received rTMS during the 24-week trial maintained stable scores on the Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB), while the scores of those who received sham treatment declined over the 24 weeks.

    Dr Emiliano Santarnecchi

    “Our electromagnetic therapeutic approach is unique in that it primarily intervenes in the electrical rather than chemical side of the brain to treat AD,” said researcher Emiliano Santarnecchi, PhD. Medscape Medical News..

    “This allows for a non-invasive, safe and precision-based therapeutic approach, and it has the ability to adapt to each patient through an innovative approach,” he added.

    Santarnecchi is director of the precision neuroscience and neuromodulation program at Massachusetts General Hospital in Boston, Massachusetts, and co-founder of Sinaptica Therapeutics, which is currently developing an AD treatment system called the SinaptiStim-AD System in which TMS is used to treat patients with UN D.

    The study was published online October 25 in Brain.

    Preserved cognition

    Several small randomized controlled trials have compared rTMS to a dummy treatment for patients with AD. In 2018, a meta-analysis of these studies found that rTMS significantly improved cognition in people with AD, but showed no difference between the two groups in terms of functional performance.

    The current Phase 2 trial, with lead investigator Giacomo Koch, MD, PhD, enrolled 50 patients with AD from the Santa Lucia Foundation Hospital in Rome, Italy, between February 2018 and April 2020. Koch is also co-founder of SinaptiStim and director of the non-invasive brain stimulation laboratory of the Santa Lucia Foundation in Rome.

    Patients were eligible for the study if they had an established diagnosis of mild to moderate AD, met specific score criteria on the Clinical Dementia Rating Scale and Mini-Mental State Examination, and had evidence of CSF biomarkers for amyloid disease and tau for Alzheimer’s disease.

    Participants were randomly assigned to receive either rTMS or simulation on the precuneus area of ​​the brain five times per week for 2 weeks, followed by a 22-week maintenance phase during which TMS was applied once a week to all patients.

    Investigators administered rTMS (or simulation) as an adjunct to standard treatment with acetylcholinesterase inhibitors and measured brain cortical activity with EEG at each treatment.

    Investigators who were blinded to the study group assessed patients with several cognitive and functional scales at baseline, 12 weeks, and 24 weeks.

    At 24 weeks, those who received the rTMS maintained a stable score on the CDR-SB, a global measure used to assess cognition and to stage the severity of dementia, while those who received the sham TMS experienced a drop in scores.

    “TMS treatment slowed cognitive decline by 82% during the trial compared to those who received the sham treatment. This represented a treatment difference in CDR-SB of 1.3 points (P = 0.009), which is considered clinically significant,” the researchers note.

    Those who received TMS also had better functional outcomes compared to those who received sham treatment. On the ADCS-ADL (Alzheimer’s Disease Cooperative Study–Activities of Daily Living) scale, those treated with TMS showed improved cognitive function compared to those who received sham treatment, with an estimated mean change in scores ADCS-ADL of -0.7 for the treatment group and 7.5 for the sham group, demonstrating a difference of 108% between the treatment and sham groups at 6 months.

    Patients who received the TMS also performed better on the Alzheimer’s Disease Rating Scale – Cognitive Subscale (ADAS-Cog) trial and the mini-exam. mental status (MMSE), demonstrating a slowing of functional decline, with an estimated mean change in ADAS-Cog score of -0.67 for the treatment group and -4.2 for the sham group. The estimated mean change in MMSE score was 0.30 for the treatment group and 1.8 for the sham group.

    Eight patients reported mild adverse events, such as mild headache, scalp discomfort, and neck pain/stiffness. Most of these effects disappeared on the day of surgery.

    The fact that the treatment group had minimal declines on several measures of cognition and was clinically stable during the study and improved, rather than decreased, on the primary outcome measure of functional ability (ADCS-ADL) is an impressive feat for any therapeutic in a randomized, double-blind, placebo-controlled study in AD, Santarnecchi said.

    The researchers target the precuneus as the main node of the default mode network, which has been shown to be impaired in AD patients in the early stages and even in the preclinical phases of AD.

    “We are impacting synaptic plasticity at the micro level and network connectivity at the macro level,” Santarnecchi said. “These electromagnetic pulses are able to fire neurons where we are targeting, inducing plasticity in that region of the brain. Essentially, you can think of this as rewiring and reconnecting around the growing damage caused by the [AD] to preserve both cognitive and functional abilities,” he noted.

    The researchers hope that, pending replication of the results in a larger sample, the new app will be approved by the US Food and Drug Administration (FDA) for use in patients with Alzheimer’s disease.

    No direct link to results

    Commenting on the findings of Medscape Medical NewsAlvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and medical director of the Deanna and Sidney Wolk Center for Memory Health at Hebrew SeniorLife, said while he believes the study presents a number of strengths, including the recruitment of well-characterized patients with tau biomarkers for AD, and while articulating a clear and compelling hypothesis, the researchers did not link the change in gamma activity or mode network connectivity. by default directly to the results.

    Dr. Alvaro Pascual-Leone

    “They recognize modulation activity in the default mode network, but it would be nice to see if the clinical benefit is taken into account by this activity, because that is the hypothesis of the study,” he said. -he declares.

    Pascual-Leone was not involved in the study and conducted his own research into rTMS and AD.

    He pointed out that the group that received a sham treatment “decreased to a surprising degree” over the 6-month trial, as evidenced by the assessment scores, which seems to explain that the differences between the two groups seem more pronounced.

    “The main clinical effect seems to be a lack of progression in the treatment group, but 6 months is a relatively short period, so it would be nice to see how these results hold up over a longer period. -he declares.

    The researchers plan to conduct a larger multicenter study of TMS in patients with AD in 2023.

    “We have received FDA Breakthrough Device designation after sharing our approach and supporting data and will discuss with the agency the design of a pivotal study that has the potential to replicate and hopefully , even improve those results,” said Santarnecchi.

    The study was funded by the Brightfocus Foundation and the Italian Ministry of Health. Santarnecci reports having patents on noninvasive brain stimulation applications in neurodegenerative diseases.

    Brain. Published online October 25, 2022. Full text

    Eve Bender is a Pittsburgh-based medical journalist who has previously written for Psychiatric News, Neurology Today, and MedPage Today.

    For more information about Medscape Neurology, join us on Facebook and Twitter.

    Diagnosis is the Next Battleground: How Dr. Lal Pathlabs, SRL is Trying to Hold On Mon, 24 Oct 2022 06:48:24 +0000

    As large conglomerates gradually enter the diagnostics market, dominant players such as Dr. Lal Pathlabs and Metropolis Healthcare are developing plans to maintain their leadership position in the game.

    The diagnostic majors are eyeing inorganic growth for their network expansion, further intensifying the competition. For example, Dr. Lal PathLabs acquired Suburban Diagnostics in 2021 for Rs 925 crore in Western India. It also plans to expand into South India with a reference lab in Bangalore which is a major market for Metropolis Healthcare.

    In the same year, Metropolis Healthcare acquired Dr. Ganesan’s Hitech Diagnostic Center (Hitech) and its subsidiary Centralab Healthcare Services (Centralab) for Rs 636 crore. SRL completed the acquisition of DDRC-SRL JV in April 2021, allowing it to consolidate its market share in Kerala and strengthen its B2C presence.

    Hyderabad-based Vijaya Diagnostics also said it plans to expand into Andhra Pradesh and Telangana, and is keen to acquire lucrative diagnostics companies in eastern India to explore business opportunities. In the region.

    Diagnostics companies are focusing on new segments and trying to penetrate new geographies that have become all the more important after the pandemic. Dr. Lal PathLabs focuses on Tier II and Tier III cities, especially in the northern and eastern regions of India, as well as metros and Tier I cities in southern and eastern India. west of India. With covid testing no longer a profitable area, Dr. Lal PathLabs aims to invest in IT and digital and focus on wellness packages. The noted diagnostic channel also focuses on bundled and preventative health check packages.

    “We identify and focus clinical segments such as allergies, autoimmune diseases, etc. We also want to strengthen the online retail segment. As far as our expansion plans are concerned, we want to look to the South and West markets,” says Dr. Om Manchanda, Managing Director, Dr. Lal Pathlabs. “India is a very under-penetrated market. After Covid, the penetration of diagnostics will increase as the practice of medicine becomes more evidence-based, especially in Tier II and Tier III cities,” he says.

    Likewise, for SRL Diagnostics, another major player in diagnostics, the expansion of the test menu to offer more diagnostic solutions, the expansion of the network to gain market share and new customers, and the constant supply of high-quality diagnostic services continue to drive growth. Developing a strategy for growth, in FY22, SRL added over 1,000 centers to its network and in the first quarter of FY23, it added approximately 250 more.

    “These new touchpoints are part of our strategic growth plan. We are investing in our capabilities to offer services through digital touchpoints and strengthening our home collection units to respond to changing customer behavior post-pandemic,” says Anand K. CEO, SRL Diagnostics.

    According to market analysts, India’s diagnostics industry is estimated at Rs 675 billion, with the industry growing at an annual rate of 8-9%. Domestic players hold around 15% of the market share and hence there are ample opportunities for growth. Recent acquisitions by large laboratory chains and the entry of new players will allow the industry to consolidate at a faster pace.

    Metropolis Healthcare Ltd has also made clear that it aims to develop and expand the reach of oncology, prenatal testing, transplant immunology and infectious and chronic diseases through next generation sequencing and intelligence artificial.

    “To achieve this goal and catalyze optimal patient care, we have created an innovation cell for molecular genomics, super specialized pathology and the expansion of companion diagnostics. We will continue to build our capacity in different areas and look for more opportunities to offer ‘affordable’ testing to patients as we move further into Tier 2 and Tier 3 cities,” said Ameera Shah, Developer and Director. General of Metropolis Healthcare. ltd.

    Shah is aware that over the past 2-3 years due to the Covid-19 pandemic, the industry has gone through several structural changes and consumer behavior towards health has changed to a greater extent. Shah noted that new players have jumped into diagnostics and are primarily focused on the bigger cake in the “Chronicle and Wellness” segment.

    “People have become more health conscious and have started to proactively invest in health packages and want to keep tabs on their health. Therefore, our goal will now be to focus on 100% of the population, which includes chronic and wellness patients. We aim to target them through well-priced wellness packages, loyalty programs, etc. says Shah.