Worcester Medicine November/December 2021

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Volume 90 • Number 6 Published by Worcester District Medical Society November / December 2021

The Remarkable Journey from Desiccated Scabs to Genomic Vaccines Amplify Your Practice With Point of Care Polymerase Chain Reaction (PCR) Testing

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Contents

on the cover

NOVEMBER / DECEMBER 2021

Teenage Girl Having PCR Covid-19 Test photo by Milan Markovic

Game Changers in Medicine Editorial 4

Recent Cancer Advances from a Student Perspective 15

Peter T. Zacharia, MD

Charlotte Walmsley

The Remarkable Journey from Desiccated Scabs to Genomic Vaccines 5

From the Curator Breakthroughs in Medical Education 17

Anthony L. Esposito, MD and George M. Abraham, MD

B. Dale Magee, MD, Curator

Amplify Your Practice with Point of Care Polymerase Chain Reaction (PCR) Testing 8

As I See It EMR: Missed Opportunities and Unfulfilled Promises, Why Patients and Physicians Deserve Better 17

Craig Lilly, MD and Nathaniel Hafer, PhD

Teprotumumab (Tepezza), Game Changer in Thyroid Eye Disease 10 Teri Kleinberg, MD, MSc

No More Finger Sticks: Continuous Glucose Monitors 11 Nancy Sidhom MSN, ANP-BC, CDCES

Legal Consult MassHealth’s Uncivil Action 18 Peter Martin, Esq.

In Memoriam Dr. Richard L. Bishop 19

Herpes Zoster Vaccine: A Breakthrough in Preventing Shingles 12

Dr. Joel H. Popkin

Anna K. Morin, PharmD

Pushing the Evolution of Radiology: Informatics and What it Means for the Future Radiologist and Radiology Trainee 14 Tina Shiang, MD

Fred Baker, MD, FAAFP

Dr. Robert W. Finberg 19 Dr. Douglas Golenbock

Society Snippets Health Matters 22 Melissa Boucher

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Editorial Recent Game-Changing Developments in Health Care Peter T. Zacharia, MD

T

he term game changer was originally used to describe a

decisive play in a sports match. A 50-yard pass play setting up a touchdown for the eventual win during a low-scoring gridiron contest is one such example. An eighth inning, tie-breaking home run in a baseball game is another. Both would be lauded as game changers during postgame commentary on a Sunday evening sports analysis show. Important developments outside the world of sports which profoundly alter expected outcomes are also regarded as game changers.

Progress in scientific fields, and especially medicine, can often be compared to an 18-play scoring drive in football, with the information gained from the work of successive researchers and spanning decades resulting in game-changing advances. Historic examples of this include the work of several individuals during the late 19th and early 20th centuries culminating in the identification and purification of insulin for treatment of diabetes mellitus. Other game changers in medicine have been the result of astute observations by scientists and physicians whose curiosity led to development of life-improving substances and technologies. Alexander Fleming’s observation, the death of staphylococcal cultures surrounding an area of fungal contamination of a bacterial culture, had the makings of a game-changing observation, although it was not immediately recognized at the time. It would take years before the importance and life-saving significance of his observation, which eventually led to the isolation and production of penicillin, would be realized.

During World War II, Sir Harold Ridley, a British ophthalmologist, provided care for members of the Royal Air Force whose cockpit canopies shattered sending fragments of acrylic plastic into their eyes. His observation that these fragments failed to incite an inflammatory reaction inspired him to develop the first intraocular lenses for use in cataract surgery obviating the need for thick postoperative aphakic spectacles, mercifully changing the game and quality of life for millions of cataract patients during subsequent decades In this issue we examine several of the more recent game changing ideas in medicine and how they have extended and enhanced the lives of patients.

In an article entitled, “The Remarkable Journey from Desiccated Scabs to Genomic Vaccines,” Anthony Esposito, MD; and George Abraham, MD; impart the fascinating story of vaccine development beginning with the use of desiccated scabs in the practice of variolation in ancient China, jumping in time nearly 28 centuries to Edward Jenner’s work with cowpox in England, and weaving in the stories of Pasteur and others whose work led to development of other vaccines in the late 19th and early 20th centuries. They trace the path to the most recent vaccination technology using mRNA in the COVID-19 vaccine and dispelling myths and fears of mRNA integration within human DNA after injection. Along the way they also remind us of the origin of the political opposition to vaccines and compulsory vaccination in late 19th century England and the United States as well as the parallels to vaccine resistance in the news today.

In their article, “Amplify Your Practice With Point of Care Polymerase Chain Reaction Testing;” Craig Lilly, MD; and Nathaniel Hafer, PhD.; deliver an efficient summary explaining briefly the mechanism of PCR and discussing its use in various clinical applications as well

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as advances in technology. These advances have even allowed this tool to evolve into point of care PCR, helpful during the COVD-19 pandemic, no longer requiring the use of a central laboratory for analysis of specimens.

Supplementing their article is a concise and informative table listing the utility of this powerful technology which allows identification of specific organisms causing infectious disease, selection of antimicrobials to combat the infection, and monitoring the response to treatment.

Additional applications discussed for this versatile, gamechanging weapon include diagnosis of genetic disease, selection of therapy in oncology and monitoring for organ transplant rejection.

Teri Kleinberg, MD, a Worcester ophthalmologist discusses teprotumumab, a monoclonal antibody against the insulin-like growth factor I receptor which has been a game changer in the treatment of thyroid eye disease, which results in proptosis and can cause visual symptoms including double vison and loss of vision. She describes older techniques to treat thyroid eye disease prior to development of teprotumumab including lubrication, steroids, radiation and surgery. Dr. Kleinberg goes on to discuss the effectiveness of teprotumumab as determined in the multicenter OPTIC Trial, where a revolutionary treatment in reversing the proptosis and related symptoms which result from the disease were evaluated. Finally, she touches upon the sad truth which is the astronomical cost of this therapy and the limitations those fees put on its use.

Nancy Sidhom, MSN, ANP-BC, CDCES describes the game-changing role of continuous glucose monitoring in managing blood sugar levels in the treatment of diabetes mellitus and discusses advantages over fingerstick testing of blood sugar levels and the role CGM plays in educating a patient in the management of the disease. She reviews and compares three of the available CGM sensor devices and discusses studies showing the effectiveness of these devices in improving and facilitating diabetes management in patients.

Anna K. Morin, PharmD, in her article, “Herpes Zoster Vaccine: A Breakthrough in Preventing Shingles,” reminds us of the symptoms and clinical characteristics including sequelae of Herpes zoster, commonly known as shingles, which can be a devastating and very uncomfortable reactivation of the varicella zoster virus occurring more often with advancing age. She discusses the replacement of the older and less effective zoster vaccine live or Zostavax vaccine with the newer and much more protective recombinant zoster vaccine branded as Shingrix. She lists the recommendations of the Advisory Committee on Immunization Practices regarding who should get the vaccine, as well as contraindications in her article on a disease which threatens us all.

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Game Changers Editorial Continued Tina Shiang, MD, writes an article on informatics and the future of radiology. She discusses artificial intelligence algorithms developed and cleared by the U.S. Food and Drug Administration for clinical use in interpreting radiological images, but offers the opinion that AI is unlikely to replace human radiologists any time soon. Dr. Shiang encourages other radiologists to learn about and explore the field of informatics and utilization of AI to augment a radiologist’s interpretations of images for the purpose of improving patient care.

Charlotte Walmsley, a fourth-year medical student at University of Massachusetts T.S. Chan School of Medicine , gives us a student perspective on recent cancer advances after having worked at the Massachusetts General Hospital Cancer Center prior to starting medical school. She discusses the paradigm shift from the 20th-century surgery followed by chemotherapy to 21st-century treatments, which include targeted therapy and immunotherapy for cancer as well as more recently developed chimeric antigen receptor therapy, or CAR-T. She completes her article with encouraging data on the treatment of pediatric patients with leukemia and rare cancers exemplified by anaplastic thyroid cancer.

In addition to these articles discussing game changers in medicine, our society curator, Dale Magee, MD, gives us a brief history of medical education in the United States with a discussion of the first women to earn medical degrees and 19th-century educational institutions intended to train female physicians. Federic Baker, MD, FAAFP, laments the missed opportunities and unfulfilled promises of electronic medical records software, citing poor software designs and workflows. He blames dysfunctional EMR programs as a factor in physician burnout and advocates for policymakers to hold EMR vendors and third-party payors accountable for EMR shortcomings.

Peter Martin, Esq., in his column “Legal Consult” gives us an update on a recent Massachusetts Supreme Judicial Court decision regarding whether MassHealth is subject to a statute of limitations when it attempts to recoup overpayments for services rendered by a health care entity. Reassuringly, the answer is that there is a six-year limitation.

We hope you enjoy and learn from the articles in this issue, and that you continue to read Worcester Medicine which focuses on a different theme each issue. Previous issues exploring topics affecting the medical community and the general public are available on our website: www. wdms.org/publications. + Peter Zacharia is an ophthalmologist in private practice in Worcester who has been on the editorial board of Worcester Medicine for several years.

The Remarkable Journey from Desiccated Scabs to Genomic Vaccines Anthony L. Esposito, MD George M. Abraham, MD

T

he practice of immunization against communicable

diseases is centuries old. Evidence exists that by 1000 BCE, Chinese practitioners were immunizing against smallpox by grinding up desiccated smallpox scabs and blowing the material through long, silver tubes into the noses of children. Immunization may also have been achieved in Asia by scratching material from a lesion of a patient with a mild case of smallpox into the skin of a susceptible person, a practice referred to as variolation. Not surprisingly, the use of such crude preparations resulted not only in protection against severe smallpox but also in the transmission of both mild and serious infections. Variolation was also practiced in Turkey and Africa before arriving in Europe and the Americas.

Vaccine development in the west began in 1796 when Edward Jenner, a country physician, inoculated an eight-year-old boy with pus taken from a cowpox lesion on a milkmaid’s hand. A few weeks later, Jenner inoculated two sites on the boy’s arm with variolous material, either desiccated smallpox scabs or fluid from pustules. The boy remained well after that challenge as well as after a second. On the basis of 12 such experiments and other clinical cases, Jenner published a report, “Inquiry Into the Causes and Effects of the Variolae Vaccine,” in which he concluded, “the cowpox protects the human constitution from the infection of smallpox.”

It was common knowledge milkmaids were unaffected by smallpox, a disease which killed 10 to 20% of the population in towns and cities. It is also of note that others in England and Europe had immunized subjects with material containing the cowpox virus. However, Jenner was the first to expose cowpox-vaccinated subjects to smallpox and to prove vaccination protected against the disease. Jenner’s investigations, and his efforts to disseminate what he learned, led to the eventual eradication of smallpox in 1979. It is not an understatement to say that Jenner’s work and the subsequent investigations it spawned have saved more lives than any other medical intervention in human history.

Programs designed to vaccinate large populations against smallpox in the 1800s were met with criticisms and resistance based on religious, scientific and political grounds. Some of the objections were easy to understand. For example, the concept of scoring a child’s arm and exposing the open wound to infectious material from another human would have been daunting in any era. Other objections were anchored in religious beliefs

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Game Changers Descciated Scabs to Genomic Vaccines Continued (i.e., the vaccine were “unchristian”), scientific skepticism (i.e., show me the data), and common knowledge of the era (i.e., smallpox was due to putrid humors in the air). In addition, others of the period resisted because of a general distrust in medicine or because vaccinations violated their personal rights. As governments, including those in the United States, created laws known as Vaccination Acts requiring vaccination and, in some cases, included penalties for non-compliance, resistance hardened as citizens demanded the right to control their and their children’s bodies. In England, the Vaccination Act spawned the London Society for the Abolition of Compulsory Vaccination and the Anti-Compulsory Vaccination League, which campaigned against “The Vaccination Humbug” and which became the National Anti-Vaccination League. Political theater of the time included the Leicester Demonstration March of 1885 in which 80,000 to 100,000 anti-vaccinators marched with banners, a child’s coffin, and an effigy of Jenner.

Resistance to mandatory vaccination spread to the United States and, in 1882, the New England Anti-Compulsory Vaccination League was formed followed in 1885, by the Anti-Vaccination League of New York City.

Using pamphlets, court battles and fights on the floors of state legislatures, the anti-vaccinationists succeeded in repealing compulsory vaccination laws in several states. The struggle between anti-vaccinationists and public health officials was protracted in the courts and beyond. Anti-vaccinationists were responsible in 1894 for instigating riots in Milwaukee which included the stoning of ambulances and public health workers.

Beyond the political arena, the 1880s and 1890s were periods of explosive microbial discovery when many of the bacteria causing human diseases were first isolated. These diseases included anthrax, first isolated

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by Robert Koch; cholera (Filippo Pacini and Robert Koch); diptheria (Edwin Klebs and Friedrich Löffler); tetanus (Arthur Nicolaier); and tuberculosis (Koch).

Other bacteria isolated from ill humans with respiratory tract infections during the period included hemophilus (Richard Pfeiffer) and pneumococcus (Louis Pasteur).

The identification of bacteria responsible for common infections coupled with the success of Jenner’s vaccine in controlling smallpox across the globe spurred subsequent efforts to develop vaccines against a range of human maladies. Examples of early successes include the work of Jaime Ferran who, in 1885 developed a live, attenuated cholera vaccine that, when administered into soft tissues of the arm was partially effective against the disease.

Also of note are the studies of Shibasaburo Kitasato and Emil von Behring who demonstrated serum derived from immunizing laboratory animals with heat-treated diphtheria toxin could cure other laboratory animals and, in 1892, proved these same positive results when given to humans with diphtheria.

The most successful vaccine of the era was Pasteur’s against rabies, an invariably fatal infection. Studies done in 1804 demonstrated saliva from a rabid dog could transmit the disease to a non-infected one and to other animals. Later investigations showed animals

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Game Changers Descciated Scabs to Genomic Vaccines Continued injected intravenously with saliva from a rabid animal would not develop the disease. Pasteur extended this work and showed the virulence of the microbe which was causing rabies became progressively attenuated when passed from a dog to a monkey and then from monkey to monkey. On the other hand, virulence could be increased when passed from rabbit to rabbit or guinea pig to guinea pig. He showed the exposure of neural tissues from a rabid animal to dry air also produced an attenuation in virulence. In 1885 using emulsions of spinal cords from rabid rabbits that had been kept in dry air for varying times, he “treated” successfully, i.e., administer a 9-year-old boy bitten by a rabid dog, thus demonstrating the efficacy of post-exposure prophylaxis. In 1886, Pasteur reported he had similarly treated 350 patients with only one fatality.

Pasteur’s contributions included discovering methods to attenuate the virulence of animal pathogens leading to vaccines that prevented outbreaks which decimated flocks and herds.

He demonstrated sheep and other domesticated animals could be successfully vaccinated with an anthrax bacillus exposed to high temperatures or carbolic acid and that chickens could be protected from fowl cholera by inoculation with old cultures of the bacterium that caused the disease. Unaware of the impact of genetic changes on a microbe’s virulence, he attributed attenuation to a depletion of some element crucial to growth. Pasteur’s demonstration that microbial attenuation could lead to useful vaccines became a mainstay in the subsequent development of human vaccines. By the end of the 19th and early 20th centuries, attenuated, whole cell vaccines had been developed against typhoid, plague and other bacterial diseases.

The 20th century process of vaccine development followed the paths established in the late 19th century: isolate or identify the offending microbe, identify potential virulence factors (i.e., exotoxins or capsular polysaccharides), and develop vaccines based on the administration of an attenuated microbe, the microbe’s exotoxin (e.g., inactivated diphtheria toxin or diphtheria toxoid), or a virulence factor potentially linked to a carrier molecule (e.g., protein conjugated pneumococcal, meningococcal or Hemophilus influenzae capsular polysaccharides). The development of a potential vaccine would be accompanied by trials to confirm safety and an adequate immune response followed by clinical trials to confirm efficacy or protection.

Unavailable to researchers in the 19th century, 20th-century vaccine researchers had tools to quantitate the humoral and cellular immune response to bacterial and viral antigens and to assess the effectiveness of that response in in vitro tissue cultures and in vivo animal models prior to introducing a vaccine into humans where measures of immune response, such as antibody titers, could be correlated with vaccine efficacy.

The value of the traditional process of vaccine development and introduction is highlighted by the impact vaccines had during the 20th century. The Centers for Disease Control and the National Institute of Allergy and Infectious Diseases report that prior to the introduction of effective vaccines and immunization programs,

500,000 cases of measles, 175,000 cases of diphtheria, 47,000 cases of rubella and 16,000 cases of polio occurred each year in the United States. What has been the impact of effective vaccines? In 2019, there were 1,282 cases of measles, a record high for the decade; two cases of diphtheria; and less than 10 cases of rubella reported in the United States. Polio, like smallpox, has been eradicated and a bacterium; Haemophilus influenza, type B, which only decades ago caused 20,000 infections annually and 1,000 deaths in infants and children; has largely become a disease of historical interest.

Vaccine development is a long process and 10 to 15 years are often required to move a potential vaccine through the customary stages of exploration; preclinical laboratory studies; Phase I, II and III clinical trials; and finally review and approval by the U.S. Food and Drug Administration.

In addition, the use of attenuated, whole microbes as antigens suffers from the limitation that the vaccinated host may respond to multiple antigens not relevant to protective immunity. Past pandemics have shown that vaccine development and introduction during outbreaks were not fast enough to have an impact on the disease at hand, even when the technology to produce the vaccine was available (e.g., H1N1 influenza pandemic of 2009). Indeed, recent Ebola and Zika epidemics ended before vaccines under development became available.

As we have witnessed with the current COVID-19 pandemic, the evolution of molecular biology and genetic engineering has changed the landscape of vaccine development. In early genetic vaccine development, bacteria, yeast or other cells were given the genetic sequences necessary to produce a desired antigen such as the hepatitis B surface antigen. Although the engineered cells may be able to produce substantial quantities of the antigen, the amount needed might not be met by the process. In particular, the failure to expeditiously produce a vaccine during the 2009 H1N1 pandemic led to a search for novel development and production platforms.

We have witnessed one such novel platform in action.

Within weeks following the release of the gene sequences of SARS-CoV-2, the cause of COVID-19, scientists had identified the genetic segment responsible for encoding the virus’ primary virulence factor, the spike glycoprotein. In turn, the molecular structure and chemical composition of the spike glycoprotein were quickly elucidated. Using an entirely synthetic processes, Moderna and Pfizer–BioNTech each created a vaccine that consisted of the mRNA sequence encoding a portion of spike protein; the receptor binding domain, or RBD; and a lipid envelope. In March 2020, within three months of the publication of the virus’ genome, Phase I clinical trials were underway.

Phase II and III trials quickly followed and, on Dec. 11, 2020, the Pfizer BioNTech vaccine was released under an emergency use authorization. The Moderna vaccine received the same

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Game Changers

Descciated Scabs to Genomic Vaccines Continued clearance the following week.

The platforms for synthesizing mRNA vaccines created an enormous number of doses. By the end of August 2021, approximately 350 million doses of the two mRNA vaccines had been administered to residents of the United States. Epidemiologists have estimated the two vaccines, which had demonstrated efficacies of greater than 90% in persons of all ages in reducing the risk of hospitalization and death, have saved tens of thousands of hospitalizations and lives.

The stunning introduction and efficacy of the mRNA vaccines have not been without controversy due to misinformation, especially regarding a belief that the vaccine can alter a recipient’s DNA. In fact, the mRNA injected into the muscle cells of the upper arm promptly instructs the cells to produce the RBD of the spike protein, but it does not enter the cell’s nucleus or comingle with the host’s DNA. Indeed, being a fragile molecule, the mRNA disintegrates about 72 hours after entering muscle cells. The spike RBD protein produced in response to the mRNA is seen as foreign and as such elicits a cellular and humoral immune response, the latter including the production of neutralizing antibodies. These antibodies bind to the spike’s RBD, which is responsible for attaching to host-cell receptors; the angiotensin converting enzyme, or ACE2; and initiating host-cell invasion. Thus, neutralized by antibodies, SARS-CoV-2 cannot infect targeted cells and the recipient’s DNA remains intact and unaltered.

Given the impact of global warming, the extent of human intrusion on ecosystems and the scope of international travel, the likelihood of another coronavirus or other viral pandemic appears almost certain. One reassuring lesson from the current crisis is that the scientific ability to swiftly characterize novel microbes to the atomic level is remarkable and without precedent. Similarly, the ability of dedicated researchers to elucidate interactions between microbe and host at the molecular level is equally breathtaking. Finally, the ability of governments and private industry to work together to produce and distribute life-saving vaccines is equally impressive.

In short, medical science has come a long way from using desiccated scabs to inoculate susceptible populations. However, it is worth remembering, “antivaxxers” agitating in 2021 were preceded by those in the 1800s who found the smallpox vaccine unacceptable and who resisted its introduction. So, while mRNA vaccines should be considered game changers in medicine, human nature appears sadly unyielding in its adherence to irrational, narcissistic and self-destructive impulses. + Anthony L. Esposito, MD Hospital Epidemiologist, Saint Vincent Hospital Professor of Medicine University of Massachusetts School of Medicine George Abraham, MD Chief of Medicine, Saint Vincent Hospital Professor of Medicine University of Massachusetts School of Medicine

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Amplify Your Practice With Point of Care Polymerase Chain Reaction (PCR) Testing Craig M. Lilly, MD Nathaniel Hafer, PhD

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xtraordinary advances in the ability to

rapidly and accurately determine the coding sequences of DNA have taken place in the past 25 years. A xerox-like technology called the polymerase chain reaction, or PCR, was developed that allowed minute samples to be amplified to an amount sufficient for sequencing (decoding). This advance won its inventor, Cary Mullis, the 1993 Nobel Prize in chemistry. Subsequently, the methods for determining the sequence of code letters of DNA and RNA in clinical samples has reached a new level of convenience.

PCR technologies have led to an increasing number of clinical applications and have recently been at the forefront of public health recommendations during the COVID-19 pandemic. Here, we will briefly describe how PCR works, and its potential pitfalls, followed by a description of tests available for clinicians to diagnose and manage diseases. We will also discuss the availability of these tests in a point of care format that can provide immediate access to test results at a patisent’s home or in their physician’s office.

PCR tests detect nucleic acid sequences by cyclical amplification. The specificity of the reaction is determined by a pair of “primers” that bind to sites on opposite ends of a DNA or RNA molecule. Enzymatic addition of complementary nucleotides to those of the target sequence fill in the space between the primers and generate a complementary strand comprised of nucleotides that correspond to those of the original target — i.e. guanine corresponds to cytosine. The target and complementary strands are then separated by heating the reaction mixture and the primers and then attaching both to the original target and the newly synthesized copies to generate an exponential number of copies during subsequent amplification cycles. A key feature of the method is that the copying enzyme, called a DNA polymerase, is a special in that it can withstand the repeated heating steps. It was discovered in a primitive organism that

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Game Changers

Amplify Your Practice Continued lives in hot thermal vents at Yellowstone National Park — an example of how research based on curiosity can pay off.

The sequence of the products of PCR reactions determines their chemical properties including size, charge and molecular weight.

When primer design is optimized, amplification of a single product that corresponds to a unique sequence of the target nucleic acid allows specific detection of undegraded target nucleic acid sequences in a clinical sample. Exponential amplification by increasing the number of cycles allows detection of very small numbers of undegraded target nucleic acid and is limited by inadvertent amplification of non-target sequences that compromise test specificity. Including more than one set of primers in a reaction mixture allows multiplex detection of more than one target sequence.

Traditional PCR has been supplanted by reverse transcriptase or RT-PCR in which amplification and detection are performed in a single reaction vessel. Detection of amplification- protocol- derived products, often by fluorescence or colorimetric methods, allows threshold detection for a present or absent result format or when reaction conditions are optimized such that detection signal intensity is directly related to the number of target sequences in the specimen the number of copies of the target sequence can be reported. Specificity can be increased by using a detection probe that requires sequence specific binding or the use of matrix assisted laser desorption/ionization (MALDI) technology coupled with time-of-flight mass spectrometry (TOF-MS). Many non-point of care format clinical PCR tests are classified as high complexity and require a provider order and must be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.

The flexibility and utility of PCR has led to a large and growing number of diagnostic tests. Biorepositories, such as the UMass Center for Clinical and Translational Science’s Biospecimen, Tissue and Tumor Bank, play a key complementary role by providing clinical or nucleic acid samples from normal and diseased tissue. Accordingly, while our discussion of the clinical application of PCR is intended to provide an extensive list of PCR-based tests currently available (Table 1) from our local, state and commercial laboratories, it is not intended to provide a comprehensive list of all available tests and does not focus on gene sequencing applications dependent on PCR technologies.

Clinical applications of available PCR-based tests include measurement of resistance to antibiotics, disease-specific diagnostic testing, assessment of common pathways for drug metabolism, toxicity risk assessment, measurement of response to antiviral therapies, selection of anti-neoplastic agents, and methods for monitoring rejection of transplanted organs (Table 1).

The largest category of clinical application is diagnostic testing and the largest therapeutic area is the detection of sequences specific for infectious agents (1). The high specificity of PCR testing for infectious agents is made possible, in part, by the presence of sequences not part of the human genome and allows for more easily developed dichotomous readouts than quantitative testing of human target sequences.

Limitations of test interpretation include the finding that colonizing organisms with pathogenic potential can be detected in healthy individuals by highly sensitive PCR tests. Indeed, the detection of bacterial

sequences in the blood of healthy volunteers has limited the positive and negative predictive power of broad-spectrum bacterial detection PCR assays. Clinical application has been widely adopted for some tests while others have not lived up to initial reports.

The clinical utility of quantitative PCR for monitoring responses to antiviral therapies is now well established, particularly for the management of HIV therapeutics. PCR-based detection of emerging variation of HIV sequences from a patient’s blood is now standard care for guiding antiviral treatment (2). Although viral genome tests are more complex than most antibiotic susceptibility tests, their sensitivity for detecting viral mutations is of great value for understanding and tracking variants with emerging drug resistance (3). Genotypic testing also has the advantage of detecting transitional mutations that do not themselves cause drug resistance but indicate the presence of selective drug pressure that allows proactive modification of antiviral care plans.

Application of PCR monitoring to organ rejection is attractive because both the extent of inflammatory gene expression and the presence of donor-organ-specific DNA in the serum can indicate inflammation and damage of the graft, the hallmarks of rejection. Despite the advantages of these noninvasive technologies, they have not, to date, provided information equivalent to that provided by organ biopsies (4). As of May 2021, a consensus panel found noninvasive laboratory testing using gene expression profiling, or GEP; nCounter Human Organ Transplant Panel, MMDX Heart, breath testing, (a.k.a Heartsbreath); and donor-derived, cell-free DNA testing, or MyTAIHeart Tests; can aid in the diagnosis of heart transplant rejection. However, further studies will be needed to determine the utility of these molecular diagnostic assays as a replacement for routine biopsies and other aspects of long-term management of heart transplant recipients (5).

Advances in microfluidics, detection technologies, miniaturization and the evolving availability of key reagents is enabling PCR point of care testing eliminating the need for central laboratory performance of some PCR-based tests. Experience during the COVID-19 pandemic has made the public aware of the advantages of immediate PCR test results and there is strong public support for making them available. In the absence of restrictive legislation, affordable test costs will allow accurate PCR-based tests to be performed in the office or the home. Clinical skills will need to include managing false positive and misinterpreted test results. Despite these occasional undesirable effects, we expect this wider availability of laboratory testing to lead to earlier diagnosis of many diseases and better outcomes for time-to-treatment sensitive infectious, neurological, cardiovascular and neoplastic disorders.

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Game Changers Amplify Your Practice Continued In summary, PCR tests are increasingly familiar in our clinical practices and daily lives and are best ordered and interpreted in the context of the clinical question that is being addressed. Patient-ordered testing represents a new starting point for provider-patient discussions. Clinical skill and an understanding of the limitations of these sensitive assays are necessary for the optimal use of PCR-based medical testing.

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Craig M. Lilly, MD Professor of Medicine, Anesthesiology and Surgery, University of Massachusetts Chan Medical School, UMass Memorial Medical Center, 281 Lincoln Street, Worcester, MA 01605 email: craig.lilly@umassmed.edu Nathaniel Hafer, PhD University of Massachusetts Chan Medical School, Morningside Graduate School of Biomedical Sciences, UMass Chan Medical School Center for Clinical and Translational Science and Program in Molecular Medicine references

1. Yang S, Rothman RE. PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings. The Lancet infectious diseases. 2004;4(6):337-348.

2. Hanna GJ, D’Aquila RT. Clinical use of genotypic and phenotypic drug resistance testing to monitor antiretroviral chemotherapy. Clin Infect Dis. 2001;32(5):774-782.

3. Demeter LM, Hughes MD, Coombs RW, et al. Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med. 2001;135(11):954-964.

4. Deng MC. The evolution of patient-specific precision biomarkers to guide personalized heart-transplant care.

Expert Rev Precis Med Drug Dev. 2021;6(1):51-63.

5.Wellmark. Laboratory Testing for Transplant Rejection; policy 02.04.75. Wellmark. https://www.wellmark.com/Provider/MedpoliciesAndAuthorizations/ MedicalPolicies/policies/Laboratory_testing_transplant_rejection.aspx. Published 2021. Accessed.

Table 1: Available for review in the digital edition at www.wdms.org/publications.

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Teprotumumab (Tepezza): a Game Changer in Thyroid Eye Disease Teri Kleinberg, MD, MSc

T

hyroid eye disease, or ted, is a beast with many names including

Graves’ ophthalmopathy, thyroid-related orbitopathy and dysthyroid orbitopathy. Regardless of what you choose to call this constellation of clinical findings, it is a disfiguring, debilitating and progressive disease that affects both psychological and functional well-being. TED affects 1.9 cases per 10,000 population per year (1) and can range from mild dry eye symptoms to massive proptosis, double vision and vision loss from compressive optic neuropathy. Many of us see these patients and work closely in multidisciplinary teams that may include internal or family medicine, endocrinology, ophthalmology, radiation oncology and otorhinolaryngology.

Prior to 2020, there was no medical therapy approved by the U.S. Food and Drug Administration for TED. As an oculoplastic specialist, I have had limited tools in my arsenal. Initial treatment usually consists of aggressive lubrication and treatments for the ocular surface. Clinical signs of inflammation would bring on the steroids, either oral or intravenous, along with myriad familiar side effects without meaningful improvements in reduction of proptosis or alteration of the natural progression of the disease. (2) Occasionally, I will send patients to my radiation oncology colleagues for orbital radiation to reduce inflammation. Once the clinical exam stabilizes, over sometimes two to three years, I can consider surgery for my patients. These procedures include orbital decompression to reduce proptosis, strabismus surgery to help with diplopia, and eyelid surgery for lid retraction and to improve cosmesis and eyelid closure. Infrequently, terrible compressive optic neuropathy will necessitate emergent orbital decompression along with pulse doses of steroids in the hopes of preventing irreversible vision loss.

The real game changer in this disease was FDA approval of teprotumumab in 2020. Teprotumumab, or Tepezza, is a monoclonal antibody against insulin-lik growth factor I receptor, IGF-1R, which has been implicated in the pathogenesis of this disease. (2) It is the only treatment shown to reduce double vision and proptosis in TED patients. In the phase-three multicenter OPTIC trial, 83% of treatment arm patients had reduction of proptosis of at least 2 millimeters versus 10% in the control group. A majority, 68%, of patients had reduction in diplopia versus 29% in the control group. (3) Teprotumumab has been shown to have clinically significant as well as durable treatment effects for at least one year with longer observational studies coming down the pipeline. (3) Use of this agenct involves an eight-infusion series performed every three weeks over a total treatment period of 24 weeks. Known contraindications are poorly controlled diabetes, irritable bowel syndrome, and pregnancy.

Significant side effects that occurred in over 5% of patients in the aggregate of both published studies include muscle spasms (25%), nausea

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Teprotumumab Continued

Game Changers

Left: Tepezza trial patient baseline photo demonstrating 24 mm of proptosis, eyelid swelling, conjunctival injection chemoses, and inflammation of the caruncle. Image reproduced with permission from Horizon Pharmaceuticals.

Right: Tepezza trial patient post-treatment (week 24) photo demonstrating reduction of proptosis to 19 mm and mild residual eyelid swelling. Image reproduced with permission from Horizon Pharmaceuticals.

No More Finger Sticks: Continuous Glucose Monitors Nancy Sidhom MSN, ANP-BC, CDCES

H

ave you ever tried to do something in the dark? no matter

(17%), alopecia (13%), diarrhea (12%), fatigue (12%), hyperglycemia (10%), hearing impairment (10%), dysgeusia (8%), headaches (8%) and dry skin (8%).

(3,4) It is worth noting that 89% of the treatment group completed the full course of treatment. (3,4) Unfortunately, as with most novel treatments, the most challenging part of this treatment is obtaining prior authorization and coverage from insurance companies. The estimated cost of the full series of infusions is approximately $200,000 (5). Insurance coverage of this medication will — at least in the near future — be the primary limiting factor for obtaining this game-changing treatment. + Teri Kleinberg, MD, MSc is an ophthalmologist and oculoplastic specialist in private practice at Worcester Ophthalmology Associates. She is a proud graduate of The University of Massachusetts Chan Medical School Class of 2010. She participates in medical student teaching through the Leadership & Professionalism fourth-year elective course in the Department of Family Medicine. She is also on the executive board of the Massachusetts Society of Eye Physicians and Surgeons. She can be reached at 508-421-2010 or via email at tkleinbergmd@ woadocs.com. references:

1. Smith, T. J., & Hegedüs, L. (2016). Graves’ disease. New England Journal of Medicine, 375(16), 1552-1565.

2. Slentz, D. H., Smith, T. J., Kim, D. S., & Joseph, S. S. (2021). Teprotumumab for optic neuropathy in thyroid eye disease. JAMA ophthalmology, 139(2), 244-247.

3. Douglas, R. S., Kahaly, G. J., Patel, A., Sile, S., Thompson, E. H., Perdok, R., ... & Smith, T. J. (2020).

Teprotumumab for the treatment of active thyroid eye disease. New England Journal of Medicine, 382(4), 341-352.

4. Smith, T. J., Kahaly, G. J., Ezra, D. G., Fleming, J. C., Dailey, R. A., Tang, R. A., ... & Douglas, R. S. (2017). Teprotumumab for thyroid-associated ophthalmopathy. New England Journal of Medicine, 376(18), 1748-1761.

5. https://www.aao.org/eye-health/news/tepezza-nonsurgical-treatment-thyroid-eye-disease

how simple the task, you quickly find it is nearly impossible until someone turns on the light. Continuous glucose monitor, or CGM, therapy is nothing less than that light switch for so many blindly grappling through their diabetes management.

Why is CGM such a game changer? Historically, we have asked patients to manage their blood sugar value, which in truth is an everchanging number they simply cannot see. On a very basic level, it’s akin to asking someone to abide by the speed limit in a car without a speedometer. Despite the availability of fingerstick testing, it essentially provides patients limited information from single moments in time rather than the big picture they need to see. Fingerstick tests are like the few pictures you snapped on your fishing trip while CGM sensor technology is the drone video footage of your day.

From a nursing perspective, education is the center point of every patient encounter. Many concepts can be difficult to understand including glycemic index, post prandial blood sugar spikes and insulin action times. CGM allows patients to watch these difficult concepts play out in real time, usually on an app conveniently available on their phones. The continuous streaming of blood glucose data allows for a much greater understanding of blood glucose trends, cause and effect, and it allows individuals to make more informed treatment decisions throughout the day to finally reach their goal. When a patient can visualize the effects of dietary choices or exercise on their blood sugars, it acts as a powerful form of biofeedback. CGM use has led many patients to reduce insulin use, revamp dietary choices, create exercise habits and effectively instill long-sought behavior change.

Historically, CGM therapy was reserved for patients with Type 1 diabetes. Fortunately, CGM therapy is now widely covered for patients with Type 1 and Type 2 diabetes. Medicare and MassHealth cover CGM therapy for most patients on more than three insulin injections per day who must adjust insulin intake based on blood glucose data. Many commercial insurance providers cover CGM therapy for patients with diabetes regardless of insulin use.

Currently, there are several CGM sensors available for personal use which are FDA approved for treatment decisions without additional fingerstick testing: Dexcom, Abbott Freestyle Libre and Senseonics Eversense.

The Dexcom G6 sensor allows for 10 days of continuous wear. The sensor continuously updates blood glucose data to an app/smartwatch/ receiver every five minutes. Blood sugars are displayed with an arrow indicating the direction they are trending along with a graph of blood sugars. The sensor offers customizable high and low alerts but has one low alert at 55 mg/dl that cannot be switched off.

Freestyle Libre sensor allows for 14 days of continuous wear. Abbott Freestyle currently has two sensors on the market, the Libre and Libre 2.

The main difference between the two sensors is the alarm option.

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Game Changers No More Finger Sticks Continued The original Libre does not have any low- or high-glucose alert features. The Libre 2 offers customizable high and low alarms.

Both the Libre and Libre 2 are flash CGM sensors meaning the data is not continuously sent to the reader or their phone, but rather the patient must scan the sensor with the reader or smartphone to view a blood glucose reading along with the blood sugar trend and graph.

The Eversense CGM sensor from Senseonics is the first longterm implantable sensor. The sensor is generally inserted under the bicep muscle and replaced every 90 days at an outpatient visit. Advantages of the implantable sensor include 90 days of continuous wear and the ability to remove the external transmitter without needing to change the sensor.

Several studies have demonstrated that use of CGM therapy significantly lowers HbA1c (1,2). Data from 248 patients — 182 with Type 1 diabetes and 66 with Type 2 diabetes — demonstrated a significant decrease in mean HbA1c from 8.2% at baseline to 7.1% at the end of the three-month study (P < 0.001). More than half of those with initial HbA1c values >7% experienced absolute HbA1c reductions of >1%. Additionally, significant reductions in diabetes distress and hypoglycemic concerns were observed (P < 0.001) (1).

Few things are truly as rewarding as the improvement in self-management seen after prescribing CGM therapy. In my experience, it is not unusual for patients who have struggled for years with uncontrolled sugars, many with HbA1c values > 10%, to return to the office two weeks after sensor placement with near normal glucose control. I recently asked one of those patients why CGM made the difference for her. She admitted, as a mother of five children, it couldn’t be easier for her to forget to care for herself, which included the arduous task of trying to measure her blood sugars and remember to take her medications. While wearing the CGM sensor, however, she simply couldn’t ignore the high blood sugars. It directly correlated to marked improvements in medication compliance and diet.

Diabetes is a chronic complex condition associated with a long list of complications and a high treatment burden. Fortunately, this technology offers patients a non-pharmacological tool to proactively address their glucose level and improve overall glucose control thus reducing their risk of long- term complications while improving their day-to-day quality of life. + references

1. WH;, Gilbert TR;Noar A;Blalock O;Polonsky. “Change in Hemoglobin A1C and Quality of Life with Real-Time Continuous Glucose Monitoring Use by People with Insulin-Treated Diabetes in the Landmark Study.” Diabetes Technology &amp; Therapeutics, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih. gov/33470882/.

2. Wright, Eugene E., et al. Use of Flash Continuous Glucose Monitoring Is Associated With A1C Reduction in People with Type 2 DIABETES Treated with Basal Insulin or Noninsulin Therapy. Diabetes Spectrum, American Diabetes Association, 1 May 2021, spectrum.diabetesjournals.org/content/34/2/184.

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Herpes Zoster Vaccine: A Breakthrough in Preventing Shingles Anna K. Morin, PharmD

H

erpes zoster, also known as hz or shingles,

is caused by the varicella zoster virus, or VZV, the same virus that causes chickenpox (1). VZV remains dormant in the body within the dorsal root ganglia and can reactivate years later, spreading along a sensory nerve to cause HZ. Not everyone who had chickenpox will develop shingles, but immunity to VZV declines with advancing age and the risk for developing shingles rises sharply after the age of 50. An estimated 1 million people get shingles annually in the United States with approximately one out of every three people developing shingles during their lifetime. The annual incidence for HZ in the U.S. is approximately five cases per 1,000 in adults aged 50-59 years. However, the estimated annual incidence among individuals 80 years and older more than doubles to 11 cases per 1,000 (1,2). Immunocompromised individuals are at greater risk of developing shingles (2). Because the risk of reactivation of vaccine-strain VZV is lower compared with reactivation of wild-type, non-vaccine strain, VZV, children who have been vaccinated against chickenpox have a lower risk of developing HZ (3). There is limited information on the impact of the chickenpox vaccine on the rate of HZ in those who received the vaccine as an adult. The economic and public health impact associated with HZ in the U.S. is significant. Estimated annual direct and indirect costs related to not being vaccinated for HZ in the U.S. are nearly $800 million and the costs associated with HZ in those over the age of 65 is projected to be $4.74 billion by 2030, if the incidence of HZ is not decreased (4).

Shingles presents as a painful maculopapular rash that commonly develops in one or two adjacent dermatomes and presents as a single strip on one side of the body, this is localized HZ (1,3). The rash most often appears on the trunk along a thoracic dermatome as blisters or vesicle clusters that typically scab over in seven to 10 days and fully clear within two to four weeks.

Less commonly, the rash can be more widespread and affect three or more dermatomes, this is disseminated HZ (1,3). Disseminated zoster generally occurs in those with compromised or suppressed immune systems and can be difficult to distinguish from chickenpox. Symptoms of pain, itching or tingling may precede the onset of an HZ rash by several days. Most individuals experience a single episode of shingles during their lifetime.

However, multiple episodes of shingles are possible.

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Game Changers

Herpes Zoster Vaccine Continued Additional symptoms of shingles can include fever, headache, chills, fatigue and gastrointestinal upset. Shingles is not contagious, however, direct contact with the fluid in the HZ vesicles can lead to infection of VZV in those who are not immune — i.e., those who have never had chickenpox nor received the chickenpox vaccine (3). These individuals will develop chickenpox and be at risk for shingles later in life. Infection with VZV is not a concern before the shingles rash blisters appear or after the rash crusts. To prevent spreading VZV to others, patients with shingles should cover the rash, avoid touching or scratching the rash, wash their hands often and avoid contact with the following high-risk individuals during the blister stage: pregnant women, infants and immunocompromised individuals (1,3).

The most common complication of shingles is postherpetic neuralgia, or PHN, which is long-term nerve pain persisting for at least 90 days following the resolution of the HZ rash. It can be so severe and debilitating that it interferes with daily life (1,3).

PHN can last for weeks, months and, rarely, for years after the rash clears. Overall, approximately 10 to 13% of persons 50 years or older who get shingles will experience PHN. Risk of developing PHN after HZ increases with age and older adults with shingles are more likely to experience longer lasting and more severe pain (2,3). Other predictors of PHN include the level of pain and the size of rash. Additional complications of HZ can include pneumonia, encephalitis, permanent pigmentation changes, skin scarring or bacterial superinfection at the site of the rash, hospitalization and, rarely, death. Shingles on the face can result in hearing or vision loss (3). In addition to being more likely to have severe, long-lasting rash, developing disseminated HZ and being at risk for re-developing shingles; immunocompromised individuals are more likely to experience complications and require hospitalization. Oral antiviral medications; such as acyclovir, valacyclovir and famciclovir; can be effective in shortening the length and severity of the rash when started within 72 hours of rash appearance but do not prevent pain or the development of PHN (1,3).

Pain medications can help manage severe pain and topical products such as wet dressings and lotions may help relieve itching.

PHN is challenging to treat and many patients do not experience adequate pain relief despite pharmacotherapy.

Vaccinating against HZ is the most effective way to prevent shingles and associated complications, including PHN (2,3).

The first HZ vaccine; Zostavax®, or zoster vaccine live ZVL; was approved by the U.S. Food and Drug Administration in 2006 but is no longer available for use in the U.S. as of November 2020.3 The effectiveness of ZVL in preventing HZ was 70% in individuals aged 50-59 years, 64% in those aged 60-69 years and 38% in those over the age of 70 (2). A newer HZ vaccine; Shingrix®. or recombinant zoster vaccine RZV; was approved by the FDA in October 2017 for the prevention of shingles in adults aged 50 and older. (5). Unlike ZVL, RZV is an inactivated vaccine comprised of VZV glycoprotein E, or gE, and an adjuvant suspension referred to as AS01B (5). Required for viral replication, gE is found on the surface of cells infected with VZV. The role of the adjuvant is to stimulate and induce a higher gE-specific, cell-mediated immune response. ZVL does not contain preservatives (5).

The Advisory Committee on Immunization Practices recommends RZV for the prevention of HZ in immunocompetent adults aged 50 years or older (2). RZV is also FDA approved for adults aged 18 years and older who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy (5). Testing for varicella antibody prior to or after administration is not required (3). RZV has not been evaluated in persons who are VZV-seronegative and the vaccine is not indicated for the prevention of chickenpox (varicella) (5). RZV is administered intramuscularly as a two-dose series at 0.5 mL each and is spaced two to six months apart. In clinical trials, two doses of RZV were 97% effective at preventing shingles and 91% effective in preventing PHN in adults aged 50 to 69. In adults 70 years or older, two doses of RZV were 91% effective in preventing shingles and 89% effective in preventing PHN, with protection continuing above 85% for at least the first four years after vaccination. (2,5). RZV is contraindicated in individuals who have had an anaphylactic reaction to any component of the vaccine or a previous dose. RZV should not be administered during an acute episode of HZ and is not recommended for use during pregnancy, in women who are breastfeeding or in severely compromised individuals as data to support use in these patient populations are lacking (2,5). While mild illness is not a contraindication to shingles vaccination, vaccination visits for patients with suspected or confirmed COVID-19, regardless of symptoms, should be postponed to avoid COVID-19 exposure (3). RZV can be administered concomitantly with other adult vaccines including influenza and pneumococcal vaccines at different anatomical sites (3,5). The ACIP recommends those who previously received ZVL also receive the two-dose series of RZV at least two months after ZVL (2). Common RZV adverse effects include pain, redness, and swelling at the injection site as well as muscle pain, tiredness, headache, shivering, fever and upset stomach. An increased risk of Guillain-Barré syndrome has been reported during the 42 days following vaccination (5).

RZV offers strong protection against shingles and PHN. Given the increased risk of morbidity, mortality and disability, as well as the significant economic and public health burden caused by HZ and PHN, all adults aged 50 or older should be counseled to receive and complete the RZV two-dose vaccine series. + references:

1. Cohen JL. Clinical practice: herpes zoster. N Engl J Med 2013;369(3):255-263.

2. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. January 26, 2018. Morbidiy and Mortality Weekly Report (MMWR), 67(3):103-108. Available at: https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm. Accessed: September 28, 2021.

3. Centers for Disease Control and Prevention (CDC). Shingles (herpes zoster).

October 5, 2020. Available at: https://www.cdc.gov/shingles/. Accessed: September 28, 2021.

4. FamuyiroT, Smith ST, Raji M. Making the case for universal herpes zoster vaccination in older adults. Ann Longterm Care 2018;26(2):27-31.

5. Shingrix® (zoster vaccine, recombinant, adjuvanted) prescribing information.

Research Triangle Park, North Carolina: GlaxoSmithKline, 2021. Available at: https:// gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Shingrix/pdf/SHINGRIX.PDF. Accessed: September 28, 2021.

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Game Changers Pushing the Evolution of Radiology: Informatics and What it Means for the Future Radiologist and Radiology Trainee Tina Shiang, MD

informatics is changing the landscape of radiology

I

t is an exciting time to be in the field of radiology. Our generation of radiologists and radiology trainees has witnessed several progressive technological advances that forever changed the way we practice medicine. In the 1900s, the internet was born and with the help of Google and various other digital resources, we have the largest spectrum of information available at just the click of a mouse (1). The 2000s brought widespread adoption of modern electronic medical records, popularization of the picture archiving and communication system, and improved standardization and integration of different health systems promoting the current model of a collaborative, team-based approach to patient care (1). Now, in the age of big data and machine learning algorithms, computer vision is offering breakthroughs in automation, optimization and efficiency that are transforming radiology and health care delivery. The possibilities are limitless, to the point where some fear artificial intelligence will make radiologists obsolete and disrupt the integrity of the medical imaging world (2,3).

Informatics is propelling major changes and is easily the hottest topic in radiology. AI algorithms have made great strides, as evidenced by the 136 U.S. Food and Drug Administration-cleared AI algorithms compiled by the American College of Radiology Data Science Institute (4). Just to name a few, these include intracranial hemorrhage detection in neuroradiology, pulmonary embolism detection in chest imaging and subtle fracture detection in musculoskeletal imaging (4). All of these have great potential in optimizing image pattern recognition and assisting the radiologist in more accurate and quicker diagnoses.

In addition, with the ongoing challenges posed by the COVID-19 pandemic, utilization of virtual learning and the remote workforce has truly taken off. On-demand video lectures such as APDR National Virtual Noon Conferences, AUR Diagnostic Radiology Resident Core Curriculum Lecture Series, virtual readouts, and virtual didactic and multidisciplinary conferences are being rapidly embraced to accommodate learning in the socially distanced setting. Remote work and virtual consultations through telemedicine provide more flexibility, convenience and safety to health care workers who are continuing to battle against the virus (2).

Despite the promising results of medical AI systems, “general artificial intelligence” that could “replicate average human intelligence” is still far from replacing the radiologist (3). The mastery that the trained radiologist has in deciphering complex image patterns and prescribing “clinical relevance in image interpretation” remains extremely difficult for computers to match, let alone surpass (3). However, AI can reduce

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the burden of time-consuming, mundane tasks often termed “scut work” such as protocoling or tracking down clinicians to communicate critical results. This would in turn buy the radiologist time and increased productivity to perform more valuable radiologic work that requires clinical expertise (3). No longer is AI constrained to the massive computing power of supercomputers. By harnessing average, cost-effective computers, AI can be accessible to everyone.

I believe the future of radiology will involve the seamless integration of technology through informatics. The radiologist-computer team will push the limits of human imagination and help us “tackle problems that doctors cannot detect and solve alone (3,5).” Informatics is changing the way radiology is practiced, and radiologists should have a voice in guiding its development. I strongly encourage radiologists and trainees to embrace every opportunity to learn, experience and immerse themselves in exploring what informatics has to offer. Although there is no imminent apocalyptic threat to radiologists’ job security, radiologists who can effectively leverage AI will have a significant edge over those who cannot or choose not to (3). As futurist Kevin Kelly astutely pointed out, “You’ll be paid in the future based on how well you work with robots (3).” We should see AI as a promising partner rather than the nefarious enemy. It should be high priority to determine the best way we can utilize innovative applications in informatics to augment the radiologist and improve patient care (3,5). my informatics journey and future plans

I had a late start in informatics, but it is never too late to pursue a new passion. Throughout residency, I strived to improve efficiency, reduce medical errors and find ways to enhance resident education. I led several quality improvement projects and collaborated with my residency program to optimize CT protocoling and improve the transparency of MRI protocols. These initiatives helped improve our clinical workflow, reduce operational inefficiencies and enhance the training of future radiologists at my institution. Through these projects, I realized many of the problems I wanted to solve necessitates bridging the gap between medical and computer science fields. After seeking out advice from practicing clinical-informaticists and an automation engineer, it became evident we had to speak the same language and develop a common ground for understanding medical and technical knowledge to collaborate effectively. To this end, this year I am taking the National

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Game Changers

Pushing the Evolution of Radiology Continued Imaging Informatics Curriculum Course-Radiology to improve my understanding of imaging informatics fundamentals and plan to further explore opportunities during informatics fellowship.

My vision is to combine my clinical knowledge in radiology, technical knowledge of computer systems and skills gained through collaborations to create optimal technical solutions for clinical problems.

I want to be at the forefront of shaping the role of informatics in radiology and as a future MSK-informaticist, I hope my colleagues in radiology share my enthusiasm in integrating radiology and informatics.

+

references:

1. Evans RS. Electronic Health Records: Then, Now, and in the Future. Yearbook of Medical Informatics.

2016;Suppl 1(Suppl 1):S48-S61. doi:10.15265/ IYS-2016-s006 2. Guilford-Blake, Roxanna. “Wait. Will AI Replace Radiologists After All?” Radiology Business, 18 Feb 2020, https://www.radiologybusiness.com/topics/ artificial-intelligence/wait-will-ai-replace-radiologists-after-all 3. Chan S, Siegel EL. Will machine learning end the viability of radiology as a thriving medical specialty? British Journal of Radiology. 2019; 92(1094):20180416. doi: 10.1259/bjr.20180416.

Epub 2018 Nov 1. PMID: 30325645.

4. “FDA-Cleared AI Algorithms.” ACR Data Science Institute. https://models.acrdsi.org/ 5. Reardon S. Rise of robot radiologists. Nature.

2019; 576(7787):S54-S58. doi: 10.1038/d41586019-03847-z. PMID: 31853073.

Tina Shiang, MD, is a PGY-5 Diagnostic Radiology Resident and Chief Resident at University of Massachusetts in Worcester, Mass. She is a future musculoskeletal radiology and intervention fellow at Brigham and Women’s Hospital and informatics fellow at the Center for Evidence Based Medicine in Boston. Email: tina.shiang@umassmemorial.org

Recent Cancer Advances From a Student’s Perspective Charolette Walmsley

P

rior to medical school, my first foray into

patient care occurred at the Massachusetts General Hospital Cancer Center, working one-on-one with cancer patients receiving first-in-human clinical trial drugs. The patients came in hopes of extending their lives or even finding the silver bullet at the cost of a host of side effects — anything from mouth sores to deadly immune reactions. Despite the high stakes and abundant side effects, the Henri and Belinda Termeer Center for Targeted Therapies was a hopeful and exciting place.

Everyone, patients and caretakers alike, knew the field of oncology was moving at light speed. Each year, groundbreaking treatments were shooting through the clinical trials pipeline, settling into clinical practice and saving lives. Observing this combination of bravery, hope, heartbreak and triumph inspired me to pursue my dream of becoming an oncologist. I would like to walk you through the recent advances in cancer treatments and hopefully instill you with some of my excitement for the field. The possibilities in oncology are truly endless.

Prior to the 2000s, first-line cancer therapy followed a similar formula: surgery, when possible, followed by chemotherapy. To the benefit of innumerable patients, this paradigm was upended following the arrival of immunotherapy and targeted therapy. Targeted therapy came on the scene slightly earlier than immunotherapy with the landmark approval of Herceptin as a treatment for early-stage breast cancer in 2006 (1). Herceptin, like other targeted therapies, is engineered to attack a specific protein on the surface of cancer cells providing a more targeted approach. In contrast, immunotherapy is a strategy centered around using the body’s natural defenses, the immune response, to target and kill cancer cells. Designated as the cancer advance of the year in 2016, the American Society of Clinical Oncology wrote: “clinical trials of promising approaches followed one after another (2).” Later that year, the U.S. Food and Drug Administration approved a wave of immunotherapies for the treatment of bladder cancer, Hodgkin lymphoma, and head, neck, and lung cancers.

However promising, a major shortcoming of immunotherapies — and a surprising turn of events for many oncologists — was the unpredictability of which patients would benefit from immunotherapy. A handful of patients would experience a major response, where others would see little to no benefit. Fortunately, the unprecedented

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Game Changers Recent Cancer Advances From a Student’s Perspective Continued success of immunotherapy continued in 2017 as new technologies were developed to detect which patients would benefit from immunotherapy based on the presence of genetic mutations (3).

In 2018, a new, groundbreaking type of immunotherapy known as chimeric antigen receptor T-cell therapy, or CAR-T, took the oncology world by storm. CAR-T is a technique that genetically reprograms patients’ immune cells to fight cancer. In this type of treatment, a patient’s T-cells are removed and genetically altered to find and kill cancer cells. Not only is it extremely efficacious in a number of patients, but CAR-T is also living therapy that continues to work over time (4).

There is no better demonstration of the power of CAR-T than its impact on pediatric acute lymphoblastic leukemia, or AL. For kids with ALL who do not respond to the first-line treatments, approximately 10%, survival is often measured in weeks. However, Kymriah, a type of CAR-T, sent 52 of 63 patients into remission in the ENSIGN clinical trial (National Clinical Trial number NCT02228096), prompting the FDA to approve Kymriah to treat pediatric ALL patients (5). This same treatment was also used on patients with recurrent non-Hodgkin lymphoma and multiple myeloma sending a large portion of those patients into lasting remission — a truly remarkable success (4). Despite the wondrous effects of CAR-T, a major drawback is the many serious and often unpredictable side effects of treatment which include inflammatory reactions and neurologic problems. Clearly no major breakthrough is without drawbacks, especially in the field of oncology.

Let’s continue. In 2019, the major advances occurred in the realm of targeted therapies, a type of treatment engineered to target a patient’s specific cancer genes or proteins. In the recent past, these therapies have been particularly efficacious for rare cancers, making up approximately 20% of all cancer cases (6). One notable example is anaplastic thyroid cancer. Known as one of the most insatiable and destructive cancers, anaplastic thyroid cancer had a median overall survival of 35% at four months, according to the Surveillance, Epidemiology and End Results database analysis (1986-2015) (7). A combination treatment of two targeted therapies, a BRAF inhibitor and an MEK inhibitor, led to durable responses in 69% of patients with recurrent anaplastic-thyroid cancer (8). That is a significant amount given the devastating prognosis of anaplastic thyroid cancer. Similar advances occurred in the treatment of soft-tissue sarcoma.

Back to our initial paradigm, we can’t leave out surgery. Given the array of new efficacious medical therapies, the role of surgery has adapted to better fit the needs of patients. Starting in 2019, clinical trials in advanced melanoma, kidney cancer and pancreatic cancer showed that treating patients with systemic therapies prior to surgery can improve outcomes and lead to more effective, less-invasive surgeries (9).

A win-win.

I hope, at the very least, I’ve expressed the exponential rise in cancer discoveries in the recent past. I also hope that my excitement for the field is evident in my words as I find enthusiasm is often contagious. Ultimately, I hope to live in a world where cancer is a chronic disease instead of a fatal one. It is truly a remarkable time to be embarking on a career in cancer medicine. +

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Charlotte Walmsley is a fourth-year medical student at the The University of Massachusetts Chan Medical School. references:

1. Bartsch, Rupert et al. “Trastuzumab in the management of early and advanced stage breast cancer.” Biologics : targets & therapy vol. 1,1 (2007): 19-31.

2. Dizon, Don S et al. “Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 34,9 (2016): 987-1011. doi:10.1200/ JCO.2015.65.8427 3. Burstein, Harold J et al. “Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 35,12 (2017): 1341-1367. doi:10.1200/ JCO.2016.71.5292 4. Heymach, John et al. “Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 36,10 (2018): 1020-1044. doi:10.1200/ JCO.2017.77.0446 5. Mueller, Karen Thudium et al. “Tisagenlecleucel Immunogenicity in Relapsed/Refractory Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma.” Blood advances, bloodadvances.2020003844. 25 Aug. 2021, doi:10.1182/bloodadvances.2020003844 6. Pal, Sumanta K et al. “Clinical Cancer Advances 2019: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 37,10 (2019): 834-849. doi:10.1200/ JCO.18.02037 7. Lin B, Ma H, Ma M, et al. . The incidence and survival analysis for anaplastic thyroid carcinoma: a SEER database analysis. Am J Transl Res. 2019;11(9):5888-5896.

8. Subbiah, Vivek et al. “Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.”

Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 36,1 (2018): 7-13. doi:10.1200/JCO.2017.73.6785 9. Markham, Merry Jennifer et al. “Clinical Cancer Advances 2020: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.”

Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 38,10 (2020): 1081. doi:10.1200/JCO.19.03141

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Game Changers Breakthroughs in Medical Education B. Dale Magee, MD, Curator

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state of medical education in the mid-19th century in the United States was poor. There were numerous schools and virtually no admission requirements, beyond having fees for courses. Medical schools taught theory but there was no clinical experience. Classes were held for about four months and the same lectures were repeated a second year. Those who passed exams were issued diplomas. Another approach was to undergo an apprenticeship for a few years and be granted a letter from the doctor certifying the apprentice’s qualifications. Even licensing wasn’t standard. For example, in Massachusetts, the Massachusetts Medical Society would have “censors” examine applicants, the Worcester District assumed this role for MMS locally, and issue certificates. A book containing the recommended reading list as well as logs of those examined are in the WDMS archives. It was not until 1894 that the Massachusetts Board of Registration in Medicine was founded.

In 1869, Charles Eliot, president of Harvard University, recommended that Harvard Medical School move to a three-year curriculum, extend the academic year and utilize written exams. He was cautioned against this because a majority of students at that time could barely write. Eliot persisted and a few years later his wish was granted. In subsequent years, the enrollment dropped by over 40%.

Students of medical education are familiar with the founding of The Johns Hopkins University School of Medical in 1893.

This raised the level of education and introduced a model that looks familiar today: a college education was required for admission, medical school started with two years of basic science and progressed to two years of clinical education using a hospital connected to the medical school.

Lost in this is the role of Elizabeth Blackwell and her sister, Emily, the first and third women in the U.S. to earn medical degrees.

Elizabeth was a strong advocate of mainstreaming medical education for women and having them attend the same schools and meet the same standards as men. But, in the mid-1860s, she became aware of the fact that women were getting a second rate education.

As a result, the two sisters started the Women’s Medical College of the New York Infirmary in 1868. They extended the length of the academic year, expanded to three years with each year progressing to new material. Clinical experience was provided by integrating their New York Infirmary for Indigent Women and Children, as well as other New York hospitals, into the curriculum. Students were examined by outside experts prior to graduation.

One of the first two women admitted to the WDMS in 1885, Rebecca Barnard, was an 1878 graduate of the Women’s College of the New York Infirmary.

As other, better-financed medical schools began admitting women, the Women’s Medical College of the New York Infirmary closed in 1899. In its tenure, however, It had not only opened doors for women but also elevated the level of medical education decades before Johns Hopkins. + he

EMR: Missed Opportunities and Unfulfilled Promises, Why Patients and Physicians Deserve Better Fred Baker, MD, FAAFP

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he joy derived from meaningful work that

positively, and perhaps profoundly, impacts people’s live inspires many to a career in medicine. Unfortunately, much of that joy is infringed upon by some of the execution and design of the electronic medical record, or EMR. According to the American Medical Association, for every one hour spent with the patient, two hours are spent on documentation. Many physicians cite the EMR as a major cause of physician burnout, particularly the often-expressed concern with the rise in perceived overwhelming non-meaningful tasks or workflows. The New England Journal of Medicine noted, “about 80% of physician burnout is really due to workflow issues and, as it turns out, the way the electronic medical records have evolved — unlike in other industries where automation has made work easier — [they] have added work.”

Nowhere is this egregious reality more evident than a scene that plays out in most physician offices, several times a day. A doctor electronically transmits a prescription during a patient visit, then the patient arrives at pharmacy where the pharmacist notes the medication is denied as insurance requires an alternative or preauthorization. Next, the pharmacist calls the physician’s office to request new orders and the physician and their staff must disrupt another patient’s visit, diverting time and resources, as they scramble for a new treatment with no clear direction of what’s available. Additionally, the initial patient must incur a delay in treatment and the added burden of having to return to the pharmacy. How is it possible that — with all the dedicated, highly trained professionals; sophisticated technology, resources and data available in real-time — inefficient and disruptive workflows can be found acceptable? The problem is not a lack of resiliency or desire on the part of the health care professional, rather much of the blame must fall on the two entities most complicit and responsible for the dysfunction — namely EMR

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Game Changers EMR Continued vendors and third-party payors, both of whom show no commitment nor priority for minimizing disruption of a therapeutic patient-physician relationship. As many physicians continue to feel overwhelmed, less valued and with far fewer opportunities to pursue the very basic, yet necessary, worklife balance they advocate for their patients, due to poor EMR designs and workflows, we will witness far more physicians retiring early, leaving medicine, cutting back on services, or see far fewer recruits pursue one of the most noble career paths. Corrections are critical to ensure patients have access to high-quality care.

Medical societies continue to pursue solutions and they must be relentless in demanding meaningful change.

Physician employers could heed the advice that for each 10% drop in task load, it’s estimated physician burnout decreases by 33%. Possibly more impactful, however, is ensuring the public and policymakers hold EMR vendors and third-party payors accountable — demanding all parties explore, share and implement ways to reduce inefficiency.

Frederic Baker, MD, FAAFP is a family medicine attending with UMASS Memorial Community Medical Group Physicians with an ambulatory outpatient practice in Holden. He is a delegate for the Mass Medical Society, a past president of the Worcester District Medical Society and a past president of the Massachusetts Academy of Family Physicians. The views expressed are those of the author and are not intended to reflect nor express the opinions of any particular organization

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Legal Consult MASSHealth’s Uncivil Action Peter Martin, Esq.

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ow long may a person wait to bring a legal claim against another? for some

especially egregious acts, such as the sexual abuse of a minor, Massachusetts law says 35 years. A civil action must be brought against the Commonwealth for the actions of a public employee within three years after the cause of action accrues.

What about actions instituted by the Commonwealth against its citizens? How about forever?

This was the issue addressed in a recent Supreme Judicial Court decision involving a MassHealth recoupment claim asserted against a home health agency. In 2005, MassHealth sent an audit notice to the Suburban Home Health Care agency but did not initiate recovery proceedings against the agency until 2016. According to the agency, in early 2006, MassHealth’s audit contractor advised the agency the audit did not disclose any issues. Nothing further happened until late 2016 when MassHealth issued to the agency an initial determination of overpayment of over $95,000. After the agency responded to MassHealth’s new audit contactor, the agency did not hear from MassHealth until September of 2019, when it received a final determination of overpayment of approximately $75,000. Shortly thereafter, the agency filed for an adjudicatory hearing with the MassHealth board of hearings.

At the same time, the agency filed suit against MassHealth, alleging MassHealth ought to be held to the six-year statute of limitations that applies to legal actions relating to contract disputes. MassHealth responded in part by arguing that since an overpayment recoupment procedure was not an “action” and the contractual statute of limitation applies only to “actions,” no statute of limitations of any length constrains MassHealth from pursuing providers for overpaid services, no matter how much time has elapsed since those services were rendered. At trial, the court ruled the agency failed to exhaust its administrative remedies, though it also found exhaustion was not required in this case, and the six-year contractual statute of limitations applied only to civil actions and not to administrative collection procedures. This case thus raises two legal issues: first, what exceptions apply to the general rule that prior to seeking judicial relief, the plaintiff must exhaust available administrative remedies; and second, is a MassHealth overpayment recovery procedure a kind of civil action to which the statute of limitations applies?

As to the first issue, the Court noted the rationale for the administrative exhaustion rule is to preserve the integrity of both the administrative and judicial processes, which allows the agency to apply its specialized expertise to the issue presented and preserves judicial resources. An exception to the rule may apply where the underlying facts are not in dispute so the issue posed is of a purely legal nature suitable for judicial resolution. An exception may apply also where the issue posed is one of wider public significance. The court ruled the exception applied to Suburban Home Health Care’s case because it did not dispute the overpayment determination or its factual basis, but solely MassHealth’s right to pursue recoupment, and because of the importance of the issue posed by the case.

Regarding the second issue, the Court evaluated MassHealth’s actions and concluded its cause of action against the agency accrued no later than 2005, when it sent the audit notice and received records from the agency. MassHealth then failed to follow up for over 10 years. The court also reviewed the purposes of statutes of limitation. Such statutes encourage litigants to commence actions while evidence and witnesses are available and before memories fade. Application of a statute of limitations to MassHealth recoupment procedures would serve those purposes, as

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In Memoriam

Legal Consult Continued

well as aligning with MassHealth’s “financial incentive to detect and recover all overpayments as quickly as possible.” Next, the court noted Massachusetts does not have a specific statute of limitation applicable to MassHealth’s recoupment efforts and in that case the analysis turns to “the essential nature of the right” at issue. Given the relationship between providers and the MassHealth program is governed by a provider agreement, the court concluded the essential nature of the right at issue was a contractual one, thereby justifying application of the six-year contractual statute of limitations to MassHealth recoupment proceedings.

The court rejected MassHealth’s contention that an overpayment recovery proceeding is not an “action” as used in the limitations statute and noted other administrative proceedings are subject to statutes of limitations. The court also noted when, in other cases, it determined that no statute of limitations was intended to apply, there was clear legislative guidance to that effect. MassHealth had argued that because the legislature had imposed a statute of limitations on proceedings involving other violations of MassHealth rules, its failure to do so with respect to MassHealth overpayment recoupment proceedings demonstrated a specific legislative intent not to so limit such proceedings. Normally, this is a compelling argument, but the court rejected it in part because “we discern no reason why the legislature would not want to impose a statute of limitations.” The court here, attributing to the legislature a state of mind founded on no specific factual findings, appears to be straining toward a desired outcome based not upon technical legal doctrine but common sense and fairness.

That conclusion is supported by the following passage, where the court addressed the obvious unfairness and impracticality of allowing an administrative agency to commence a proceeding long after the acts underlying that proceeding have taken place: “We also are struck by the absurd consequences of MassHealth’s argument. Taken to its logical conclusion, MassHealth’s argument would mean that no administrative proceeding would have a time deadline for commencement or conclusion unless the legislature expressly imposed a statute of limitations. Like Rip Van Winkle, an administrative agency could wake up 20 or even 100 years later and bring enforcement proceedings against a provider or other party doing business with the government.

We do not believe that was the legislature’s intention.”

Sometimes, the court will note an absurdity resulting from legislation and conclude the best solution is to have the legislature fix the problem it created. Here, the court seems to have been swayed by the same sense of absurdity and unfairness health care providers often feel when they discern rules of procedure unfairly burden them but do not apply to government agencies. This decision, though it may not have been arrived at through the most exacting legal analysis, comes as a welcome relief to all health care providers. They will no longer be forever at risk of MassHealth recoupment claims.

Dr. Robert W. Finberg Dr. Robert W. Finberg was the true triple threat in academic medicine.

He was a brilliant teacher, an accomplished researcher and an astute clinician. His sudden death on Aug. 30, 2021, at the age of 71 left the University of Massachusetts T.H. Chan Medical School bereft of one of the finest scholars and physicians in America. Until last year, Bob was the chair of the department of medicine.

Prior to coming to UMass, he was chief of infectious diseases at the Dana-Farber Cancer Center. Anyone who remembers the year 2000, when Bob arrived at the medical school, will recall the department of medicine was a small, albeit talented, cluster of clinicians and researchers. Bob transformed the department into a renowned provider of high-quality medical services as well as a world-class research engine with tremendous success at high profile discoveries and research funding.

Bob had numerous talents. First and foremost, he was mentor to a legion of successful academic physicians, physician scientists and other scholars. His trainees literally populated the academic community with highly talented physicians, scientists and clinician-scientists. Second, he had a consummate ability to get the job done. Whether a difficult research project or the restructuring of a clinical department, important problems were resolved under his management. It was no surprise Bob organized numerous research projects to answer the challenge of SARS-CoV-2, nor that his operation ran smoothly under his spectacular organizational skills. Perhaps Bob’s most inspiring gift to his family, friends and colleagues was the passion he had toward all aspects of life. Bob was as happy tackling the numerous challenges of the COVID-19 pandemic as the innate immune response to respiratory syncytial virus, climbing Mount Kilimanjaro or achieving a deep learning of the history of architectural innovation in the city of Chicago. Bob’s untimely death resulted in great sorrow in the UMass community. We know the pain his family feels must be far greater and wish to comfort them with the knowledge that Bob will not be forgotten. He was a great man and we will all miss him.

Douglas Golenbock, MD The Neil and Margery Blacklow Chair in Infectious Diseases and Immunology, Professor and Chief, Division of Infectious Diseases and Immunology, The University of Massachusetts Chan Medical School

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In Memoriam Dr. Richard L. Bishop On the morning of Sept. 10, we lost a giant among us: Richard Bishop, MD, preeminent and model cardiologist, teacher, administrator, thinker, humanist, husband, father and dear friend. After three years of a tenacious struggle, he succumbed to cancer – the day after his 56th wedding anniversary to Sande.

Writing about Dick means trying to think of what he didn’t do. A graduate of Tufts University Medical School, he served his residency and chief residency at Baltimore City Hospitals, leading to his cardiology fellowship at Johns Hopkins University. He arrived at St. Vincent Hospital/ Fallon Clinic in 1974, immediately established himself as an astonishing teacher to myself and my co-residents. He served as director of the non-invasive cardiology lab until 1985, at which point he became director of cardiology at St. Vincent Hospital and Fallon Clinic. In 1981, he created and directed the first electrophysiology lab at the University of Massachusetts Medical School, the institution where he remained professor emeritus until his passing.

Aside from his unquestionable role as the absolute go-to cardiologist at Fallon Clinic and St. Vincent Hospital for the most bewildering cardiac, and general medical cases, he also squeezed in many years on the boards of directors of Fallon Clinic, Fallon Community Health Plan and the Fallon Foundation – aside from co-directing the Myers Primary Care Institute, serving as vice president of Fallon Clinic, president of the St. Vincent Hospital medical staff and as the chief medical officer of St. Vincent Hospital. For many years post-retirement, he ran a high-powered, much sought after weekly journal club for the cardiology fellows and attendings.

Dick’s go-to role so frequently extended to providing many colleagues with general advice or walking them through personal crises. His care for family, friends, associates and patients was unceasingly exemplary, fueled by humanism, skill and humbleness. And somehow, his worldliness also included impressive athleticism and a simply amazing knowledge of history, philosophy, literature and the arts. This was exemplified, for example, by serving as a corporator of the Worcester Art Museum, a board member of the Worcester World Affairs Council and a casting director of the Shakespeare Club of Worcester.

My entire family spent invigorating decades with Dick and his family, sharing a ski house among many other things. Aside from the fun, and our endless discussions, it was simply astonishing to observe his truly unique ability to concentrate and watch him rigorously analyze whatever subject caught his interest. You would not want to

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have debated with him about anything, including motherhood and apple pie.

His wife, Sande, a long-time medical history contributor to Worcester Medicine, was his anchor. She and their two daughters, Crisse and Cami, their son-in-law Jeff, and their three grandchildren, were his constant source of joy.

The major teaching lecture room of St. Vincent Hospital, The Richard L. Bishop Conference and Educational Center, could not have been more aptly named. For anyone attending a meeting there, please think of Dick and his family – and be inspired.

Joel H. Popkin, MD, MACP Director of Special Services for the St. Vincent Hospital medical residency and a Professor of Medicine at The University of Massachusetts Chan Medical School.

upcoming events

December 14, 2021

Med Moth – Winter/Holiday Stories

February 16, 2022

226th Oration – Dr. Kimiyoshi Kobayashi, Chief Quality Officer, UMMHC

April 22, 2022

Ballet Hispanico at The Hanover Theatre

Stay up to date on event at wdms.org/event-calendar

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WORCESTER MEDICINE

Society Snippets Health Matters Health Matters is a television program produced in collaboration with The Worcester District Medical Society and WCCA TV in Worcester. Offering valuable information on disease prevention, treatment options, current public health issues and more, Health Matters is produced in a ½ hour interview format and the program airs on WCCA TV Cable Channel 194: Wednesday- Noon and 7:30 pm, Thursday– 7:00 pm and Friday – 9:30 am.

To view episodes of Health Matters: Click the show numbers Visit our website: https://www.wdms.org/ (Community Services/Health Matters) Show Number 213 "Mental Health in Pregnancy and the Year After Pregnancy" Host: Dr. Lynda Young and Guest: Dr. Tiffany Moore Simas Show Number 214 "Infertility and the Introduction of IVF Care to Worcester" Host: Dr. James Broadhurst Guests: Drs. Armando Arroyo, Shaila Chauhan and Katherine Rotker Show Number 215 "COVID-19 Study” Host: Dr. Bruce Karlin Guest: Dr. Robert Finberg Show Number 216 "Section 12” Host: Dr. Bruce Karlin Guests: Peter Martin, Esq., Lt. Sean Murtha and Officer Angel Rivera, Jr.

If you have an idea for a topic or guest, or wish to be a guest, please contact MBoucher@wdms.org or call 508-753-1579.

30th Women In Medicine Breakfast “Panel on Mentoring” Event held on Friday, September 24, 2021 Co-Sponsored by Physicians Insurance The Panelists

Click here to view this event

You can also visit our website: https://www.wdms.org/ (Event Calendar/Past Events)

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