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Friday, August 24, 2018

New system for effective cancer diagnosis and treatment


A research group consisting of scientists from NUST MISIS, the Technical University of Munich, Helmholtz Zentrum München, the University of Duisburg-Essen, and the University of Oldenburg has developed a system that allows doctors to both improve the accuracy of diagnosing malignant cells and to provide additional opportunities for cancer treatment. The magnetoferritin compound is the main element of this new system. The research article has been published in Advanced Functional Materials.
The lack of accuracy (“contrast”) in imaging is a common problem of non-invasive diagnosis. “Contrast agents”, compounds that are introduced into the body before a diagnosis procedure to enhance the response and make affected cells more visible on a tomograph, can be used to solve this problem in magnetic resonance imaging (MRI). Paramagnetic gadolinium particles and superparamagnetic iron particles are among these agents. However, even in small quantities, these substances – alien to the human body – can potentially be dangerous.
“The international research team, including Dr. Ulf Wiedwald, a visiting Professor at the NUST MISIS Biomedical Nanomaterials Laboratory, has developed a unique injection diagnosis system based on magnetoferritin. The developed system will significantly improve the quality of MRIs and optical diagnosis”, — said Alevtina Chernikova, Rector of NUST MISIS.
Magnetoferritin is a compound consisting of endogenous human protein (ferritin) and a magnetic nucleus. The development and testing of the compound was conducted following the existing protocol for the synthesis of magnetoferritin, but was improved for the effective capture of tumor cells. The high concentration of magnetoferritin in tumor tissue made it possible to obtain a hypoallergenic contrast agent that is perfectly compatible with the human body.
“An intravenous injection of magnetoferritin has been proposed. Then, spreading with the blood flow, [the magnetoferritin] will be captured by the targeted tumor cells. As has been shown in a large number of studies, these cells actively capture transferrin – the protein responsible for transport of iron in blood. The same receptors are capable of capturing magnetoferritin as well. Once they get into the lysosomes of targeted cells, the magnetoferritin will further enhance the contrast signal”, — commented Dr. Wiedwald.
The system will also allow doctors to conduct therapy on tumor formations. If cancerous cells are identified, they can be targeted by an electromagnetic field or light, which will lead to their heating and subsequent death.

How Does Immunochemistry Work?


What is Immunochemistry?

Immunochemistry is a branch of chemistry that involves the study of the components and functions of the immune system such as the nature and interactions of antigen-antibody.
Immunochemistry involves the use of simple, rapid, robust yet sensitive automated methods for routine analyses in clinical laboratories. This biochemical field brought about a phenomenal change in laboratory and commercial testing with the invention of immunoassay equipment and a wide range of immunological reagents.
The beginning of immunochemistry dates back to 1790 when Edward Jenner discovered the vaccination against small pox. Almost 100 years later, in 1890, Emil von Behring, the German physiologist, discovered serum antibodies to cure diphtheria and tetanus. From there on, many researchers contributed to the field of immunochemistry by introducing crucial immunohistochemistry and immunocytochemistry techniques.
Enzyme-linked immunosorbent assay (ELISA), Immunology testing method in 96 wells microplate. Image Credit: Jarun Ontakrai / Shutterstock
Enzyme-linked immunosorbent assay (ELISA), Immunology testing method in 96 wells microplate. Image Credit: Jarun Ontakrai / Shutterstock

Immunohistochemistry (IHC)

This involves the use of monoclonal and polyclonal antibodies on histologically processed tissue sections in order to spot specific antigens in a healthy or diseased tissue. IHC makes use of labeled enzymes such as peroxidase and alkaline phosphatase and even colloidal gold at light microscopy and electron microscopy levels in the diagnosis of cancers and in surgical pathology. The steps involved in IHC are (i) deparaffinization of the tissue sections, (ii) use of hydrogen peroxide or free avidin for quenching of endogenous, enzymes peroxidase and alkaline phosphatase, (iii) retrieval of the antigen, (iv) blocking of non-specific binding sites, (v) binding with primary antibody and biotinylated secondary antibody, (vi) detection using polymer labeling. (vii) addition of the chromogen substrate DAB, and (viii) counterstaining, dehydration and covering of the slide.

Immunocytochemistry (ICC)

This branch involves the microscopic study of cell samples in a suspension or cells grown in a monolayer. Here, the staining process is the same as IHC wherein the enzymes catalyze the deposition of a dye at the antigenic sites within the cell sample. In ICC, the expression of protein in a cell or group of cell also aids in understanding its intracellular localization. ICC assays are of two types, i.e. the direct ICC and indirect ICC assay. The difference between these two assays is the use of secondary antibody. In indirect ICC assay, the cell samples undergo incubation with a primary antibody and secondary antibody whereas in direct ICC, secondary antibody incubation is not carried out.

Applications of Immunochemistry

Apart from the use of IHC in identifying prognostic markers in cancer, it is used to predict response to therapy, to identify infections as well as in muscular and neurodegenerative disorders. On the other hand, ICC, which involves the collection of cytological direct smears, is effective in identifying cancers such as metastatic merkel cell carcinoma and in lung adenocarcinoma.

Future of Immunochemistry

Many research studies have emphasized that IHC will play a significant role in the coming years. Genomic IHC would be used in targeted therapy to identify proteins and to develop better recombinant monoclonal antibodies. Immunochemistry is rapidly emerging as a reliable field that can aid in diagnosis of infectious and neoplastic processes and as a guide to appropriate therapy.

Demonstrating rapid immune system development in newborns


Using new analytical techniques, researchers from Karolinska Institutet in Sweden have shown for the first time the dramatic development of the human immune system after birth.

Our immune system protects us from infection by inactivating the invading bacteria or virus.
It recognizes invaders as being non-self through protein-protein interactions on the cell surface and elicits an immune response in which the invader is inactivated by the binding of antibodies or destroyed by cells of the immune system.
Importantly, the immune system remembers the pathogens it has previously encountered, allowing it to respond more rapidly when the same agent invades in the future.
Before birth, a fetus is mostly sterile. From the first intake of breath, a baby begins to be colonized by a host of bacteria and viruses.
In response, its immune system starts to change dramatically in order to protect it from this hostile new environment.
Studying the changes that occur in the immune system of new-borns has previously been limited to analyses of blood samples taken from the umbilical cord immediately after delivery.
The development of new immune cell analysis techniques that can be performed on samples of only a few drops of blood has enabled researchers to investigate changes to the neonatal immune system over a longer period.
Now, a team at the Department of Women’s and Children’s Health, Karolinska Institute, used mass cytometry in combination with extensive plasma protein analysis techniques to monitor the development of the immune system during the first 12 weeks of life in 100 babies.
The changes were found to follow a very similar pattern amongst all the babies studies, beginning in the lungs, gut, skin and mucosa; all the areas in contact with the outside world. The research was recently published in the journal, Cell.
This is the first time we’ve pinned down how the human immune system adapts itself to birth and the new environment…We saw drastic changes in the babies’ immune system between each sampling, which shows that it is highly dynamic early in life.”
Dr Petter Brodin, Lead Researcher
The research also highlighted that babies with abnormal gut flora also demonstrated a disorder of the immune system.
Next, the team plans to study immune development in more babies and continue to monitor them into childhood to determine whether there is an association between immune development and conditions such as diabetes, asthma and inflammatory bowel disease.
“Our results are important for better understanding the infection-sensitivity of newborn babies and the risks of premature birth”, said Dr Brodin.
If we can monitor the development of the immune system and steer it in different directions, we make it possible to prevent autoimmune diseases and allergies, which are partly related to the development of the immune system, and to even develop better vaccines, tailored to the neonatal immune system”.
Dr Petter Brodin, Lead Researcher

Top VA EHR project leader resigns, says agency taking effort in new direction


Genevieve Morris, chief health information officer in charge of the Cerner transition at the Veterans Affairs Department, posted her resignation letter addressed to VA Secretary Robert Wilkie and HHS Secretary Alex Azar on Twitter Aug. 24, effective immediately.
Ms. Morris served as CHIO at the VA’s Office for EHR Modernization for about one month. She was on detail from her position as principal deputy national coordinator, where she led interoperability efforts at HHS’ ONC.
In her letter, Ms. Morris said she appreciated the opportunity to serve at the VA, but that the agency’s leadership “intends to take the EHR modernization effort in a different direction than we were headed.” Ms. Morris did not provide additional information.
“Since my service as CHIO was always intended to be an interim solution, I am offering my resignation to the administration effective immediately,” the letter reads.
The VA recently established the OEHRM to guide its transition to a new Cerner EHR. The agency has previously said it is working closely with the Defense Department, which is also switching to Cerner but has faced criticism over the new systems’ capabilities.
Ms. Morris’ resignation comes just days after the departure of OEHRM CMO Ashwini Zenooz, MD, effective Sept. 4.

Mission Health questioned for quick call on muni bonds


Mission Health’s handling of its municipal debt is becoming a growing headache for the North Carolina system, which is in negotiations to be purchased by HCA Healthcare.
The system’s plan to call debt it issued a little more than a year ago at a significantly lower price than it was sold for has investors in the debt crying foul, even if Mission is following the terms of the offering statement for the $100.3 million in borrowing.
Asheville-based Mission’s July 2017 issuance was sold in August 2016 without fanfare.
But because it set the coupon on the debt at 5%, the bonds were priced at a premium of 104.4 to 122.4, yielding $18.7 million above par. Mission plans to call the bonds back as part of its sale to HCA at a cool 100, meaning Mission or its buyer keeps the difference.
After the announcement of its plans, the bonds have since lost up to 15% of their value, and investors are skeptical.
One of them, Joseph Rosenblum, director of municipal credit research for the asset management firm AllianceBernstein, said he has a lot of unanswered questions. Chief among them is when Mission began its negotiations with HCA.
“There was a long process in there between the time we looked at the bonds to the time the bonds were delivered much later,” he said, “and then just shortly after that, the announcement that the system is selling itself to the for-profit. I’m raising the question of, ‘What was the timing of all of that?’ I’m unsure. All I can say to you is bondholders are pretty unhappy.”
According to a written statement from Rowena Buffett Timms, Mission Health’s senior vice president of government and community relations, at the time the bonds were offered and sold, Mission was not having any material discussions with HCA or any other healthcare entities related to specific mergers or acquisitions. Mission signed a letter of intent with HCA in March of this year, which the health system pointed out was well after the offering and sale of the applicable bond series.
Rosenblum said investors are not only upset with Mission, but with the North Carolina Medical Care Commission, which issued the bonds on Mission’s behalf. In the past, he said he’s observed North Carolina’s state regulators taking a more hands-on approach to bond issuances, but that doesn’t appear to be the case here.
In the future, Rosenblum said he’ll approach municipal bonds in North Carolina “with a little bit more skepticism.”
Kelly Haight, a spokeswoman for the North Carolina Department of Health and Human Services, which includes the commission, said the commission is merely a conduit issuer, and does not specify call provisions included in the bonds.
Mission said the bonds’ offering prices, coupon rates and yields were dictated by the underwriters it hired to sell the bonds, not by Mission or the commission, which “only accepted and approved the coupon rates and offering prices and yields offered by the underwriters,” Buffett Timms wrote in a June 12 statement.
Most municipal bonds contain provisions that allow issuers to redeem them before their final maturity date, usually 10 years. They also commonly contain extraordinary redemption provisions that allow the bonds to be redeemed in the event property is damaged—a hospital burns down, for example—or if a law change renders the project unfeasible. Mission’s 2017 series included both, that allow it to redeem its bonds at par under those circumstances.
Mission’s 2017 series also contained a provision that allows Mission to redeem the bonds at par if the health system is purchased or merges and does not take action to make its bonds taxable.
That latter so-called “taxability” clause is what caught bondholders off guard, as the sale of a not-for-profit health system to a for-profit entity is relatively unusual, said Bill Oliver, industry and media liaison with the National Federation of Municipal Analysts. Taxability call provisions are more common in corporate-backed bond deals, but less common among not-for-profit healthcare providers, he said.
The situation will likely cause investors to be more cautious about the redemption provisions for all types of bonds, especially if they are originally issued at premiums.
“It isn’t until you get burned like this that you start looking for something like this the next time,” Oliver said.
In response to a flood of questions from investors about how Mission plans to handle the situation, Mission said the call provisions were “clearly and full disclosed” to investors. The health system also said it has included the special tax call provision in its tax-exempt, publicly offered bond deals since 1998. Some of Mission’s top bondholders, according to Bloomberg, include TIAA, Franklin Templeton Investments, AllianceBernstein, Vanguard and BlackRock, who likely are managing on behalf of individual investors, many of whom likely live in North Carolina.
Even if Mission’s deal with HCA doesn’t ultimately take place, Oliver said the bonds are unlikely to regain their value, since the possibility of a merger would still exist.
“At that point, the market is going to be suspicious,” he said.
Meanwhile, HCA issued bonds on Aug. 23 from which the hospital chain said it intends to generate net proceeds of nearly $2 billion, a portion of which will go toward “general corporate purposes, which may include acquisitions.”
Julie Henry, a spokeswoman for the North Carolina Healthcare Association, wouldn’t say whether the current situation could affect the success of future bond issuances by not-for-profit hospitals in the state.
“There are many factors that affect bond issuances, particularly in today’s volatile healthcare environment, so it is difficult to speculate on the impact of one acquisition on the rest of the state,” she wrote in an email. “We are fortunate to have well-managed public and private hospitals in North Carolina making long-term investments in their communities to improve our state’s economic health and the health of our citizens.”

DOJ takes Anthem to court on Medicare Advantage fraud probe noncompliance


The Department of Justice is asking a court to force Anthem to turn over information related to an ongoing fraud investigation involving the insurer’s Medicare Advantage plans that brought in nearly $215 million using retrospective chart reviews over a two-year period.
Anthem, meanwhile, argues investigators are overstepping their authority by asking for information that is protected by attorney-client privilege and falls outside the scope of the DOJ’s probe.
The legal spat may be a precursor to more substantial litigation as new court filings also reveal federal prosecutors may be close to filing a complaint against the insurer.
The two sides have reached an impasse following several letters exchanged between the DOJ and Anthem’s attorneys. The legal squabble revolves around a civil investigative demand (CID) issued (PDF) to Anthem March 22 by the U.S. Attorney for the Southern District of New York. Prosecutors requested depositions from Anthem’s corporate representatives about how the company calculated risk adjustment data, particularly around Medicare Advantage beneficiary diagnosis codes.
This week, New York prosecutors filed a petition of summary enforcement with the U.S. District Court for the Southern District of New York requesting that Anthem comply with the demand. That same day, a federal judge ordered (PDF) Anthem to explain why a court order should not be issued.

Under the MA program, insurers are reimbursed by the federal government based the overall health of each beneficiary. Diagnosis codes are used to determine how much is necessary to care for each patient.
Prosecutors say their investigation is focused on whether Anthem violated the False Claims Act by failing to ensure diagnosis codes were valid while taking hundreds of millions of dollars in federal reimbursement.
Court documents show Anthem obtained more than $102 million in additional risk adjustment payments in 2014 from the Centers for Medicare & Medicaid Services following a retrospective chart review using a third-party vendor known as Verscend while incurring just $18.1 million in “program expense.” In 2015, a retrospective review brought in more than $112 million on an $18.8 million cost.
“Each dollar Anthem spent on its retrospective chart review program generated more than $5 in additional risk-adjustment payments,” the DOJ said in its petition (PDF).
The DOJ said one reason for the high profitability may be because Anthem “chose to disregard” whether Verscend’s results identified certain codes already sent to CMS were invalid.
Anthem has resisted turning over information about the retrospective reviews. After receiving the March demand, Anthem challenged the U.S. Attorney’s Office request for testimony involving internal auditing procedures Anthem used to determine which diagnosis codes to submit to CMS, the company’s policies and training to ensure codes submitted were valid, and any personnel Anthem relied on to ensure compliance with those policies. Anthem argued the requests were overly burdensome, vague and ambiguous.
Prosecutors later agreed to limit the scope of the testimony. In a letter (PDF) to Anthem’s attorneys on Aug. 1, U.S. Attorney Geoffrey Berman said the investigation is focused on conduct related to the DOJ’s prior case against UnitedHealthcare in prosecutors claimed the insurer submitted erroneous diagnosis codes without conducting reasonable diligence.
The DOJ abandoned that whistleblower lawsuit in October and abandoned most of a second case against UnitedHealthcare that included similar allegations. Several other insurers, including Humana, Cigna, Health Net and Aetna have been swept up in the DOJ’s probe.

In its response, Anthem’s attorney Jim Bowman, a partner at O’Melveny & Myers, maintained the government’s request would “require dozens of witnesses and several months to provide accurate and complete testimony.” He also argued Anthem has “cooperated fully with the government’s investigation from the outset,” but the company ended an agreement to waive its right to dismiss litigation after prosecutors indicated they intended to file a complaint.
“In early 2018 … DOJ informed Anthem that a ‘decision to move forward has been made’ and that SDNY would move forward with ‘drafting the complaint and filing the case’ against Anthem related to its chart review practices,” Bowman wrote (PDF).
In a subsequent letter (PDF), Bowman said Anthem is “baffled” by the DOJ’s “repeated refusal to explain how the testimony you seek relates to the subject matter of your investigation.” He added that prosecutors have declined “no fewer than ten separate requests” to meet with Anthem’s legal team.
“There is no basis for Anthem to refuse to provide testimony on an issue directly relevant to this investigation,” Berman wrote in an Aug. 10 letter (PDF).

CVS, Walgreens Stress Face-To-Face Care Amazon Doesn’t Yet Have


While Amazon’s entrance into pharmacy captivates customers and Wall Street, brick-and-mortar rivals Walgreens and CVS Health are stressing their face-to-face connections to patients.
Walgreens is testing myriad partnerships and this summer launched a digital marketplace that links its customers to medical care providers and their prices beyond services inside the drugstores. And CVS Health is touting its relationships with medical care providers and the potential to add more services once its acquisition of the health insurance giant Aetna is completed in the coming weeks.
Without mentioning Amazon by name, the strategies unfolding at CVS, Walgreens and Walmart are designed to stress the patient connection beyond the ability to order something online and have it delivered overnight or within hours.
“With a physical presence in almost every community across the country, we have the unique ability to meet patients where they are and provide the care and services they need either face to face or with the unique set of virtual and physical delivery service capabilities that extends our physical presence in real time to meet their needs,” CVS Health CEO Larry Merlo told analysts earlier this month on the company’s second quarter earnings call. “You see, it’s not simply about selling products. It’s about delivering quality care and driving superior outcomes, both of which require expertise that our clients and members have come to trust.”
CVS operates more than 1,100 MinuteClinics staffed by nurse practitioners and isn’t ruling out offering more services at its more than 9,800 drugstore once its deal with Aetna is completed. CVS, like Walgreens, has relationships with medical care providers in the communities it serves and Walmart is reportedly discussing a partnership with the health insurer Humana, which has been gobbling outpatient care sites across the country. These local ties are what CVS and Walgreens view as key to the move away from fee-for-service medicine to value-based models that measure health outcomes and ensure medical care is delivered in the right place, in the right amount and at the right time.
So far, Amazon bought the small online pharmacy PillPack in June and earlier this year launched its Basic Care brand of over-the-counter medicines. And Amazon is working with Berkshire Hathaway and JPMorgan Chase & Co. on improving healthcare for 1 million employees.