ACMS Bulletin March 2023

Down Syndrome:

It’s Mitochondrial and It’s Treatable Doctor Mode vs. Patient Mode

MArCh 2023

What is the Proposed Patient Safety Board, and How Can It Can Benefit Physicians

Cardiac expertise for your patients.

When your patients need the best possible specialty care, AHN has physicians like Dr. Lally and his team of cardiovascular experts as a part of our nationally recognized heart program.

Dr. Lally provides patients with customized treatments for optimal outcomes. He sees patients at North Fayette and Sewickley.

Francis Lally, MD, FACC

Cardiologist

Locations: North Fayette 200 Quinn Drive, Suite 210

Pittsburgh, PA 15275

Sewickley 301 Ohio River Boulevard Suite 301

Sewickley, PA 15143

Specialties : Coronary artery disease, structural heart disease, and cardiovascular disease prevention

To refer your patient, call (412) DOCTORS.

Most major insurance plans are accepted.

Allegheny County MediCAl SoCiety

Opinion Departments

Editorial....................................5

• Spring Nourishment Deval (Reshma) Paranjpe, MD, MBA, FACS

Associate Editorial ..................8

• Doctor Mode vs. Patient Mode

Andrea G. Witlin, DO, PhD

ACMS Article ..........................10

• What Is the Proposed National Patient Safety Board, and How Can It Benefit Physicians?

Karen Wolk Feinstein, PhD Jewish Healthcare Foundation

Editorial ..................................12

• Medical Historic Vignette:

Sir Godfrey Hounsfield and CT

Richard H. Daffner, MD, FACR

Perspective ............................16

• Down Syndrome: It’s Mitochondrial and It’s Treatable

Michael G. Lamb, MD

Foundation Featured Grant Recipient ................................22

• Family House

ACMS Honors .......................24

ACMS Holiday Luncheon ......26 On

Materia Medica ......................28

• Daprodustat: The First Oral Agent for the Treatment of Anemia in Chronic Kidney Disease Maley Zents, PharmD Candidate and Tucker Freedy, PharmD, BCPS

Legal Summary.......................32

• The Benefits of Pre-Litigation Mediation

Lourdes Sanchez Ridge

ACMS in the Press ................34

Lessons from Babies with Trisomies .......................37

• Dr. Marta Kolthoff

ACMS Meeting Schedule ......40

John Hyland, MD

John Hyland, MD specializes in Radiation Oncology.

2023

Executive Committee and Board of Directors

President

Matthew B. Straka, MD

President-elect

Raymond E. Pontzer, MD

Secretary

Keith T. Kanel, MD

Treasurer

William Coppula, MD

Board Chair

Peter G. Ellis, MD

DIRECTORS

Term Expires 2023

Michael M. Aziz, MD

Micah A. Jacobs, MD

Bruce A. MacLeod, MD

Amelia A. Paré, MD

Adele L. Towers, MD

Term Expires 2024

Douglas F. Clough, MD

Kirsten D. Lin, MD

Jan B. Madison, MD

Raymond J. Pan, MD

G. Alan Yeasted, MD

Term Expires 2025

Anuradha Anand, MD

Amber Elway, DO

Mark Goodman, MD

Elizabeth Ungerman, MD

Alexander Yu, MD

PAMED DISTRICT TRUSTEE

G. Alan Yeasted

COMMITTEES

Bylaws

Raymond E. Pontzer

Finance

William Coppula, MD

Nominating

Raymond E. Pontzer, MD

Medical Editor Deval (Reshma) Paranjpe (reshma_paranjpe@hotmail.com)

Associate Editors

Douglas F. Clough (dclough@acms.org)

Richard H. Daffner (rdaffner@acms.org)

Kristen M. Ehrenberger (kehrenberger@acms.org)

Anthony L. Kovatch (mkovatch@comcast.net)

Joseph C. Paviglianiti (jcpmd@pedstrab.com)

Andrea G. Witlin (agwmfm@gmail.com)

ADMINISTRATIVE STAFF

Executive Director

Sara Hussey (shussey@acms.org)

Vice President - Member and Association Services

Nadine M. Popovich (npopovich@acms.org)

Manager - Member and Association Services

Eileen Taylor (etaylor@acms.org)

Co-Presidents

Patty Barnett Barbara Wible

Recording Secretary Justina Purpura

Administrative & Marketing Assistant Melanie Mayer (mmayer@acms.org)

Director of Publications Cindy Warren (cwarren@pamedsoc.org)

Part-Time Controller

Elizabeth Yurkovich (eyurkovich@acms.org)

ACMS ALLIANCE

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Doris Delserone Treasurer

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EDITORIAL/ADVERTISING

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Spring Nourishment

Deval (Reshma) PaRanjPe, mD, mBa, FaCs

Although snowflakes are still falling, the blustery winds of March will soon give way to April, and if all goes well, flowers and fair weather. All the better, I think, to dodge the pollen and explore the culinary offerings of Pittsburgh as the sun returns to our city for a long sojourn.

Here’s a brief roundup of the new kids on the culinary block, and some openings to look forward to:

Blue Sky Kitchen and Bar

211 North Whitfield Street, East Liberty

Eatbluesky.com

412-941-1232

Enjoy killer craft cocktails and casual fare while enjoying outdoor patio seating and a game of cornhole as the weather warms! Four kinds of chicken sandwiches, burgers, Banh Mi, Chimichurri Cheesesteaks and Shazam Shrimp Tacos await, all served with shoestring fries. In the mood for something lighter? Seven entrée salads plus a variety of inventive apps and dips ensure that there is something for everyone. Sweet potato tater tots with chipotle romesco sauce and Peruvian shrimp with Aji Amarillo sauce are

just a few of the offerings. A seriously decadent and hearty brunch menu cements Blue Sky’s status as a solid all-around choice.

Sally Ann’s

136 Sixth Street, Downtown (Cultural District)

Sallyannspgh.com

412-338-1876

Wed-Fri Breakfast and Lunch; Brunch Sat-Sun. No reservations.

You know there will be love involved when the chef (Richard DeShantz) has named his restaurant after his mother. Sally Ann’s serves “elevated childhood favorites” and offers an espresso and regular bar, arcade games, and retro décor. Enjoy sandwiches like the custard battered Monte Cristo with jalapeno jam, the Pastrami Reuben with housemade sauerkraut, or the whipped ricotta toast with date jam, pistachio, and mint. The requisite crispy chicken sandwich, grain bowl, salad, and avocado toast are also on offer. Patio dining available.

Continued on Page 6

Mambo Italia

424 Broad Street, Sewickley Village

Mamboitalia.net

412-741-3777

Dinner 4pm onwards, closed Monday. Reservations recommended. BYOB.

And ready to enjoy in the near future:

Barcelona Wine Bar (coming soon)

922 Penn Avenue (the site of the former Sharp Edge Bistro)

Those mourning the loss of the Sharp Edge Bistro can take consolation in the 2023 arrival of this chain wine and tapas bar. With locations in major cities across the Eastern Seaboard, Pittsburgh is the next outpost for this oft-acclaimed business. Its branch location in Boston is a mecca for afterwork food and wine connoisseurs of all ages, and the vibe is respectable, elegant and mature. A seasonal menu and award-winning Spanish and South American wines make this something to look forward to!

Kura Sushi (coming soon)

Former South Side Works Cinema Location

The Derby (coming soon)

Butler Street, Lawrenceville

This new offering from partners John Schiavo and Joe Piccirilli (who co-owns the excellent 424 Walnut restaurant nearby) aims to provide a geographic tour of Italy and Italian-American dishes. The menu is limited but well curated and includes many Italian-American favorites and takes advantage of a wood burning pizza oven that reaches temperatures greater than 900 degrees. A special highlight is a traditional Italian-American Sunday dinner for parties of 4-6 ($40pp) that includes soup, salad, pasta, meatballs, sasusage, bread, cannoli or gelato, and grapes.

Conveyor belt sushi comes to Pittsburgh! The novelty alone warrants a visit and provides a reason to brave the South Side (just kidding—this place is relatively far from the recent troubles on East Carson Street). Kura is a national chain with a set formula, but this formula includes such things as Takoyaki (fried octopus balls), yellowtail cheek, softshell crab tempura, udon, ramen and a variety of Japanese desserts.

The Derby rises from the ashes of the venerable Hambone’s, a venue which hosted comedy and music for 35 years before the sudden passing of the owner, Jeff Holt, in 2019. The Derby will be a bar and restaurant serving smash-burgers and fries. More importantly, the new owners plan to resurrect the live music, comedy and game nights Pittsburghers loved there.

Wishing you a wonderful Spring sharing meals with family and friends old and new.

Doctor Mode vs. Patient Mode

anDRea

G. Witlin, DO, PhD

Being a patient, especially a patient with a chronic, long term forever disease is daunting. To be real, it’s the most difficult job I’ve ever had. Most of us have experienced the other side of the spectrum, i.e., being the treating physician to a colleague or their family. We recall those experiences as challenging at best and fraught with conflicts of interest at worst. I was introduced to the concept of professional courtesy as a student. At the time, it meant no charge for office visits. Other “perks” followed - curbside consults during rounds, sneaking in for no-documentation visits after regular office hours, pilfering pharmaceutical samples rather than filling written prescriptions. Proper documentation as we know it today was purposefully absent. If there was no record, it didn’t happen. Illness and absence from our practices weren’t condoned. Correspondingly, on those rare occasions when we had “legitimate” appointments, we were uncomfortable in the waiting rooms and following the “rules” we laid out for our patients. No doubt, this blurring of the lines contributed to the false bravado and sense of invincibility that continues to haunt the medical profession to this day. We weren’t ever truly allowed to be “normal” patients, i.e., patients who hurt and cried and worried.

We constantly fought living in that vulnerable zone. Accordingly, my “bad” habits progressed.

During the early years, I tried to “assist” my colleague who was the rounding medical doc for our multispecialty group. At the time, I was hospitalized for a presumed DVT and my anticoagulation was being titrated with old fashioned unfractionated heparin. I asked my nurse to give me my PTT results throughout the night rather than to awaken my colleague. The following morning both the nurse and I got reprimanded. My colleague was especially displeased as he had slept on the couch so that his wife wouldn’t be disturbed. Unfortunately, patient mode wasn’t always so glib.

Years later as my personal medical issues multiplied and their respective complexity increased, I found myself trapped between those formative years of “doctor mode” behavior and the trepidation of sliding into “patient mode”. Instead of allowing myself to be a patient, it was as if I was on the outside looking in. I was once again, the young house staff on rounds reciting the “perfect” history hoping to curry favor with my senior resident or attending. I couldn’t help my years of training as I regurgitated my history as if I was writing an impeccable note or submitting a case report to a

medical journal. At times, I presented a detailed written summary. In my mind, I imagined that it would be helpful and appreciated. Very occasionally, my docs showed appreciation for the meticulous, comprehensive summary. But more often than not, I was shunned or treated dismissively. My recitation was too perfect and thus many times not believed. At times, I purposely omitted a minor yet potentially awkward factoid. Correspondingly, I was rarely asked theoretically sensitive or embarrassing questions. This routine backfired when a senior faculty member/sub specialist instrumental for my ongoing care accused me of “reading the book” and parroting the history. I was beside myself. That particular physician refused to see me again because his time would be consumed by his pending, coveted academic promotion. To add insult to injury, none of his “junior” colleagues nor his peers would question his judgment and assessment. That experience set back my care and eventual correct diagnosis for seven years.

Those seven years were beyond arduous. Every now and then I would muster enough courage to venture back into patient mode. The “good” docs would validate some of my complaints and would encourage me

to seek additional assistance that invariably ended without a therapy plan. Unfortunately, I also experienced intermittent unprofessional behavior. One subspecialist literally walked out midpoint of my scheduled office visit to go to her previously scheduled promotion and tenure interview. Another dispassionately referred to my treating subspecialists as “the quacks on the other side of the river”. (No, not one of the three rivers). The subspecialist who had initially diagnosed and treated me for 6 prior years equivocated and rescinded his diagnosis and treatment. At long last, my “doctor mode” finally prevailed and I ultimately found a new team that treated me with respect and allowed me to finally lapse into “patient mode”. My mind unwittingly reverts to my years of practice and how patients like myself disrupted schedules. So, I float back into doctor mode and attempt to figure things out and delay asking for help. The reality is that I’m now that

troublesome patient that I loathed. I feel bad because I always manage to develop a disease flare or some other complication.

There are also occasions in patient mode when I totally lose control of my emotions. My husband jokes about trusting me to go to visits unaccompanied. A favorite story involves our trip to an out of the way, small, community hospital ER at 4:30AM. Neither of us was pleased with the journey that was necessitated by my clumsiness. I had missed the last step on route to investigating a phantom kitchen noise disturbing my sleep. He dropped me off curbside while he parked the car. I hobbled in on crutches in severe pain looking for anyone who could provide assistance. The first person I encountered was a rather large security guard not happy with me wandering behind the counter. He asked what I was doing…my response, “what the f*** do you think I’m here for”. He was ready to kick me

out and bar me from receiving care when my husband arrived back on the scene and calmed everyone down.

Over the years, I’ve been a sieve for researching and scrutinizing my various medical issues. I’m always several steps ahead attempting to decipher some new meaning or therapy option. But there are also times when I drift back into patient mode and minimize or deny the inopportune symptoms of a pending flare. The learned panic and PTSD associated with patient mode become overwhelming.

In graduate school I was enamored by our lecture on the JAK/STAT pathway and how it was named for the two-headed Roman god, Janus. I often think about Janus, his two opposing heads, the god of beginnings, transitions and endings as I transition through my experience from doctor healer to vulnerable patient. The parable seemed fitting when I was recently prescribed a JAK inhibitor. Regrettably, my time in patient mode has multiplied exponentially. The transition is replete with emotional swings and vulnerability. It’s become infinitely more difficult to maintain the wall between the two and “appear” professional and pleasant at all times. Regrettably, I’ve recently observed several older physician friends and relatives who have completed that transition and no longer have a voice or ability to participate in their care. That is my worst fear.

What Is the Proposed National Patient Safety Board, and How Can It Benefit Physicians?

KaRen WOlK Feinstein, PhD PResiDent anD CeO, jeWish healthCaRe FOunDatiOn anD PittsBuRGh ReGiOnal health initiative

For over 25 years, the Pittsburgh Regional Health Initiative (PRHI) has been seeking solutions to the problem of preventable medical harms and supporting the region’s leaders in advancing healthcare safety. PRHI has piloted initiatives that have demonstrated success in reducing harms, but sustained efforts have fallen short, leading to a shift in tactics: a new focus on policy change at the federal level and the Regional Autonomous Patient Safety (RAPS) initiative focused establishing the Pittsburgh region as a hub for healthcare technology innovation. Both come at a time when our healthcare systems and our providers have been contending with unprecedented strains and stresses.

The Burden on Providers

Much has been emerging regarding the increasing impact of the COVID-19 pandemic on patient safety. With a recent report by the Office of the Inspector General(1) and a New England Journal of Medicine study(2) both showing high rates of harm prior the pandemic, the recent outlook has unfortunately only gotten worse. A New England Journal of Medicine piece in February 2022(3) described “substantial deterioration” in patient safety measures during COVID-19, outlining how gains in prevention of healthcare-acquired infections realized prior to the start of the pandemic have vanished. Undoubtedly, the pandemic’s strain on the healthcare workforce has had a direct effect on the safety of patients and workers. Staffing shortages, burnout, supply chain issues, poorly implemented technology solutions, and other factors continue to overburden workers and have pushed many providers to leave the profession(4).

Physicians deserve a healthcare system that is better designed for patient care and

optimizing safety. Performing workarounds because devices and systems do not integrate properly and are not user friendly has become commonplace, but this practice can also be a critical point for introduction of errors. Overly complex data collection and reporting add burdens on providers and often result in data “siloes” that are unable to communicate across systems, a fertile ground for errors that lead to harm. Our systems are simply not designed to support workers in providing safe, effective, efficient care.

Providers must not be asked to do more in this current climate. Instead, we need to employ autonomous solutions and use human factors engineering principles to build a better work environment with better equipment to achieve safe, optimal care. Such technologies and practices widely deployed in other industries have made incredible strides in safety. Even within medical specialties such as anesthesia, technology and human factors approaches have been embraced to mitigate the potential for harms. It’s time for the rest of health care to benefit from these advances that support providers in delivering the safest care possible.

A New Federal Solution

Over the past two years, the Pittsburgh Regional Health Initiative has helped to guide a coalition of leaders in health care, technology, business, academia, and other industries in a united push for federal action to address the deficiencies in our current systems. This past December, U.S. Representative Nanette Barragán (D-CA) responded by introducing H.R.9377 – the National Patient Safety Board (NPSB) Act of 2022(5), legislation to establish an independent federal agency dedicated to preventing and reducing healthcare-related harms. This landmark legislation is a critical step to improve safety for patients and healthcare providers by coordinating existing efforts within a single agency solely focused on addressing safety in health care through data-driven solutions. Modeled in part after the highly successful National Transportation Safety Board and Commercial Aviation Safety Team, the NPSB will serve as a nonpunitive, collaborative, independent agency that will guarantee a data-driven, scalable approach to preventing and reducing patient safety events in healthcare settings and alleviate strain on providers.

Responsibility for aspects of patient safety is currently spread across an array of government agencies. The result is a fragmented, uncoordinated response and siloed data that hinder our ability to identify precursors to harm and prevent future harms. A key feature of the NPSB is an interdisciplinary, public–private Healthcare Safety Team, which would identify patterns and causes of errors that are happening in healthcare settings across the U.S., with the sole purpose to identify scalable solutions focused on addressing problems such as medication errors, wrong-site surgeries, hospital-acquired infections, errors in pathology labs, and issues in transitions across care settings. By leveraging interdisciplinary teams of researchers and new technologies, including automated systems with AI algorithms(6) and the benefit of human factors engineering, the NPSB’s solutions would help to relieve the burden of data collection at the frontline; ensure that devices and equipment—including electronic health records—are engineered with compatibility and the end user in mind; and, perhaps most importantly, detect precursors to harm. Individual healthcare systems are already using advanced analytics and machine learning technologies to improve safety across their facilities, but these advances are not broadly shared. An NPSB will promote dissemination

of patient safety solutions nationwide so that systems large and small can benefit from them.

Overrides and customizations to address safety issues that arise after a system is implemented cost time and money and compromise safety. Healthcare facilities and providers deserve to be confident that the equipment and systems they purchase have been thoroughly tested for safety and effectiveness. Given the persistent burden that staffing shortages are putting on our healthcare system and our providers, it is imperative that we take the burden off the frontline by focusing on autonomous solutions and building better systems using human-factors engineering.

How You Can Help

Provider support is key to the success of any patient safety improvement effort. The NPSB Advocacy Coalition invites you to learn more about how an NPSB can support physicians in providing safe, high-quality care while minimizing the burden on the front lines. Visit npsb.org for information and resources on how an NPSB can make health care safer, learn how your organization can join the Coalition, and contact your elected officials to express support for reintroduction of NPSB legislation in the current term. Let your colleagues know about this effort.

The RAPS initiative launched in February to bring together the local health systems, providers, tech innovators, and academics to work on establishing the Pittsburgh region as a hub for developing solutions that will ease the burden on providers. Learn more at https://bit.ly/3KI1vky

There will be future pandemics. There will be future workforce crises. We all need to amplify our request for progress and powerful solutions. We need the power of autonomous solutions to make health care safer. An NPSB is key to making any meaningful change. We invite you to support this critical effort.

References

(1) \Office of the Inspector General. (2022, May). Adverse events in hospitals: a quarter of Medicare patients experienced harm in October 2018. https://oig.hhs.gov/oei/ reports/OEI-06-18-00400.pdf

(2) Bates, D. W., et al. (2023). The safety of inpatient health care. N Engl J Med, 388(2):142-153. https://doi.org/10.1056/ NEJMsa2206117

(3) Fleischer, L. A., et al. (2022). Health care safety during the pandemic and beyond — Building a system that ensures resilience. N Engl J Med, 386:609-611. https://doi. org/10.1056/NEJMp2118285

(4) Hodkinson, A., et al.(2022). Associations of physician burnout with career engagement and quality of patient care: systematic review and meta-analysis. BMJ, 378:e070442. https://doi.org/10.1136/bmj2022-070442

(5) Congress.gov. “Text - H.R.9377 - 117th Congress (2021-2022): National Patient Safety Board Act of 2022.” December 1, 2022. https://www.congress.gov/ bill/117th-congress/house-bill/9377/text

(6) Classen, D. C., et al. (2023). Bending the patient safety curve: how much can AI help? npj Digit. Med. 6:2. https://doi. org/10.1038/s41746-022-00731-5

(7) Agency for Healthcare Research and Quality. (2019). Human factors engineering. https://psnet.ahrq.gov/primer/ human-factors-engineering

Medical Historic Vignette: Sir Godfrey Hounsfield and CT

RiChaRD h. DaFFneR, mD, FaCR

Wilhelm Konrad Roentgen, a German physicist, discovered x-rays in November 1895 and reported his findings to the Würtzburg Physical Medical Society in December of that year1. Less than two months later, the first medical x-rays of a broken forearm were obtained at Dartmouth University. Over the next eighty years refinements in the practice of radiology resulted in improved safety for patients and operators of x-ray equipment as well as a wide variety of newer applications and techniques in the field.

Radiographs (x-ray images) were (and still are) superb for diagnosing lung diseases as well as most fractures and bone lesions. However, when it came to studying the brain or the solid organs of the abdomen it was necessary to opacify those structures which could be opacified with either positive contrast or air to see if a disease process was displacing the normal organs. Physicians longed for the ability to see the body’s organs from the earliest days of radiologic practice. It would take the innovative thoughts of a British engineer, who like Roentgen was not a physician, to bring those desires to fruition.

Sir Godfrey Hounsfield (Fig. 1) was born August 28th, 1919, in Suttonon-Trent, in Nottinghamshire, England.

As a child he was fascinated with electrical gadgets and machinery that he found on the family farm. While attending school he excelled in physics and mathematics. In 1939 he joined the Royal Air Force volunteer reservist squadron 89, where he learned the basics of electronics and radar, that would prove critical to the allied victory in World War II. Following the war, in 1946 he attended Faraday House Electrical Engineering College in London. There, he combined practical experience with theoretical study. In 1949 he began work at EMI (Electric and Musical Industries, Ltd - the same company that made the Beatles famous), where he researched guided weapon systems and radar and became interested in computers. In 1958, he helped design the first commercially available all-transistor computer in Britain, the EMIDEK 1100.

In 1960, Hounsfield had an idea that one could determine what was inside a box by taking x-ray readings at all angles around the object. He began constructing a computer that could take input from those x-rays at various angles to create an image of the object in “slices”. This led him to propose what we now know as computed tomography (CT). Hounsfield was unaware of the work Allan Cormack (1924–1998), a South African physicist had done on the theoretical mathematics for such a device. Hounsfield built a prototype scanner and tested it, first on a preserved human brain (Fig. 2), then on a fresh cow brain from a local butcher shop, and then on himself. On October 1st, 1971, the first successful CT brain scan was performed in London on a patient with a cerebral cyst. In 1975 he built the first whole body scanner for EMI.

Fig. 1. Sir Godfrey Hounsfield 1919–2004)

Fig. 2. Hounsfield’s prototype scanner with a section of brain

The principles of image formation with CT evolved from the work of Austrian mathematician

Johann Radon (1887–1956) (Fig. 3), who, in 1917, while working on gravitational fields, postulated that the image of a 3-dimensional object could be reconstructed from an infinite number of 2-dimensional projections of that object. His theories would have to wait until the computer age for implementation. In 1959, William Oldendorf (1925–1992) (Fig. 4), a neurologist at UCLA declared his goal was “to scan a head through a transmitted beam of x-rays, and to reconstruct the radiodensity patterns of a plane through the head” using Radon’s mathematical formulas. Hounsfield followed in their footsteps.

In diagnostic imaging there are four “classic radiographic densities –gas (air): black; fat: dark gray; water (soft tissue) gray; and metal (bone): white. The brain, heart, muscle, and abdominal organs all appear in various shades of gray, which are, for the most part, indistinguishable from one another. The principles of CT are identical to those of x-ray physics. Whenever an x-ray beam passes through an object, some of it is absorbed, some is scattered, and the rest passes through to form an image on a piece of film or a digital detector plate. The degree of absorption can be mathematically measured from the amount of radiation reaching the detector and is referred to as the absorption coefficient. Absorption coefficients vary for different tissues within the body. The human eye is limited in how many shades of gray it can discern. Computer technology, on the other hand, can measure the actual absorption coefficient and portray the differences in an unlimited number of shades of gray. In CT, absorption coefficients are measured in Hounsfield Units (HU), where water is the standard

and is given the value of 0, bone being the most dense is 1000, and air, the least dense is -1000 (Table 1). This allows us to directly see the organs of the interior of the skull, thorax, and abdomen, whereas in the pre-CT era, we would opacify those structures we could opacify (GI tract, urinary tract, blood vessels, and ventricles of the brain) and look for impingement, distortion, or displacement

CT had an immediate impact on the practice of medicine, and the numbers of CT machines quickly proliferated throughout the world. CT immediately made a number of diagnostic imaging procedures obsolete, such as conventional

Fig. 3. Johann Radon (1887–1956)

Fig. 4. William Oldendorf (1925–1992)

Table 1. Hounsfield Units (HU)

From Page 13

tomography, pneumoencephalography, lymphangiography, and Sweet’s eye locating intraocular foreign bodies. Furthermore, the technology of the CT machines themselves continued to evolve, becoming faster and more efficient in being able to portray body organs with greater accuracy. The computer-generated images used in the 1977 movie Star Wars prompted Dr. Michael Vannier, a radiologist at the Mallinckrodt Institute of Radiology in St. Louis, to inquire of George Lucas if his computer algorithms could be adapted to CT imaging. Lucas shared the algorithms with Dr. Vannier, who used them to develop multiplanar (sagittal and coronal) and 3-D reconstructions which are now commonplace components of every CT scan.

Other applications include combining CT with PET (Positron Emission Tomography) scans for more accurate localization of tumors and infections. PET scanning uses cyclotron generated isotopes that emit positrons. These isotopes show the increased use of glucose by tumors and infections. In addition, CT is used for image- guided interventions such as performing precise tissue biopsies or even in the placement of intraosseous orthopedic screws2. Finally, the virtual autopsy (“virtopsy”) was developed in Europe as an alternative to the traditional postmortem examination. The virtual autopsy preserves the body by performing a head-to-toe nondestructive data-gathering study. It is particularly useful for those areas that are difficult to assess such as the upper spine or on bodies that have undergone advanced decomposition.

By injecting intravenous contrast material, the cardiovascular system can be visualized. Numerous studies have shown that the virtual autopsy has an accuracy of approximately 99% when compared to the traditional autopsy3

Godfrey Hounsfield received many honors, including Commander in the Order of the British Empire (1976), and the Nobel Prize in Physiology or Medicine, which he shared with Allan Cormack (1924–1998) (Fig. 5) in 1979. He was knighted by Queen Elizabeth II in 1981. He retired from EMI in 1986 and accepted a consulting professorship at the Mallinckrodt Institute of Radiology, where he continued his work on applications of CT scanning as well as improvement in the efficiency of CT machines. After returning to England, he used the prize money from his Nobel to build a personal laboratory in his home. Hounsfield died at KingstonUpon-Thames, Surrey, in 2004 at the age of 84.

Wilhelm Konrad Roentgen and Godfrey Hounsfield were two nonphysicians whose discoveries and ingenuity have radically changed not only how we diagnose diseases but also how we treat patients. In 1895, Roentgen’s discovery provided us with a means to examine a patient on the inside. In 1971, Hounsfield’s ingenuity gave us an entirely different and improved means of making that examination. The CT imaging algorithms that Hounsfield developed facilitated and formed the basis of magnetic resonance (MR) imaging that we use today.

References

1. Daffner RH. Roentgen and the discovery that changed medicine. ACMS Bulletin Nov 2020, pp 331–333.

2. Sciulli RL, Daffner RH, Altman DT, Altman GT, Sewecke JJ. CT-guided Iliosacral screw placement: technique and clinical experience. Am J Roentgenol 2007; W 188:181-192.

3. Flach PM, Thali MJ, Germerott T. Review. Times have changed! forensic radiology - a new challenge for radiology and forensic pathology. Am J Roentgenol 2014; 202; W 325–334.

Dr. Daffner is a retired radiologist, who practiced at Allegheny General Hospital for over 30 years. He is Emeritus Clinical Professor of Radiology at Temple University School of Medicine. He is also an amateur historian.

Fig. 5. Allan Cormack (1924–1998)

March Is Trisomy Awareness Month

Down Syndrome: It’s Mitochondrial and It’s Treatable

miChael G. lamB mD

“Mitochondrial dysfunction plays a primary role in the neurodevelopmental anomalies and neurodegeneration of Down syndrome subjects.” That statement came from Drs. Mollo and Nitti’s group in the Department of Molecular Medicine at the University of Naples in the June 2019 issue of Frontiers in Genetics. Two years earlier, Valenti et al noted that “dysfunctional mitochondria and mitochondrial dependent activation of intracellular stress cascades are critical initiating events in many neurodevelopmental and neurodegenerative diseases including Down syndrome.” Helguera et al at the University of California in 2013 stressed that “mitochondrial dysfunction and oxidative stress are common features of Down syndrome”. More recently a 2021 study out of Spain (M. Pilar Bayone-Bafalvy et al) had the title “Down Syndrome is an Oxidative Phosphorylation Disorder”. In this paper they state that “Down syndrome is the

most common genomic disorder of intellectual disability and is caused by trisomy of the 21st chromosome. Several genes in this chromosome repress mitochondrial biogenesis”. These are just a few of the many published articles linking Down syndrome to defects in oxidative phosphorylation secondary to mitochondrial dysfunction. Decades ago, famed geneticist and co-discoverer of trisomy 21, Jerome Lejeune postulated that Down syndrome would turn out to be a metabolic disease. Some mitochondrial metabolic disorders are treatable, and others are potentially treatable. Down syndrome has thus at the very least become a potentially treatable metabolic condition.

One would think that this type of discovery would be heralded and make medical headlines. It did not and it is not clear why not. In fact, it can safely be stated that most pediatricians, internists, obstetricians, and family medicine specialists are unfamiliar with this literature even though it is extensive. The lack of familiarity with this research even includes physicians working in “Down Syndrome Clinics”. It’s not because this data is relatively new, because this research goes back to more than 20 years ago with work done by S.H. Kim that demonstrated decreased levels of mitochondrial respiratory enzymes in Down syndrome fetuses and adults. Since then, the increase in studies involving mitochondrial dysfunction,

mitochondrial dysmorphology, and even mitochondrial therapies related to Down syndrome has been exponential and yet physician awareness of these reports has been minimal. Most of these reports have been in genetics, pharmacology, molecular medicine, biochemistry, and neuroscience journals and that may be part of the problem. In the past 20 years, multiple review articles on these topics have been published but none of them are in the 4 major pediatric journals: The Journal of Pediatrics, JAMA Pediatrics, Lancet Child and Health, and Pediatrics. One wonders why a topic with this much biochemical and genetic research and involving a common disabling pediatric condition has apparently been ignored by the major pediatric journals.

A lot of the initial work regarding the relationship between Down syndrome and mitochondrial dysfunction was done in mice with trisomy 16 (a Down syndrome animal model). These studies uniformly showed mitochondrial enzyme deficiencies, a decreased amount of mitochondrial DNA, defects in oxidative phosphorylation, reduced energy production (i.e. high energy phosphate compounds), increased oxidative stress, abnormal mitochondrial cristae, a reduction in mitochondrial membrane potential, and abnormal cytoarchitectural ordering of mitochondria. Studies in human Down syndrome cells cultured in vitro have confirmed the results observed in the trisomy 16 mouse models. These

Dr. Jerome Lejeune the co-discoverer of Trisomy 21.

abnormalities were exhibited at various ages (fetus, child, and adult) in several different Down syndrome cell types including amniocytes, neuronal stem cells, fibroblasts, brain cells, cardiac myocytes, blood monocytes, blood lymphocytes and skeletal muscle cells. The study of cultured neuronal stem cells by Mollo and Esposito et al showed mitochondrial dysfunction as early as seven days and a marked tendency to form glial cells rather than functional neuronal cells. The study involving skeletal muscle was an in vivo study using phosphorus magnetic resonance spectroscopy. The cardiac myocyte studies suggested that more severe mitochondrial dysfunction was associated with the presence of congenital heart disease. The fact that mitochondrial abnormalities were evident in fetal, childhood, and adult cells of various types points to the mitochondrial abnormalities being congenital and in all cell types.

The in vivo study demonstrates that this problem with mitochondrial function is a significant issue in live patients and not just found in cultured cells.

The study of mitochondrial disease in Down syndrome is not confined simply to cell morphology, biochemistry. and cell physiology. Detailed genetic studies have also been a part of this research. As far back as 1995, Abruzova published on the role of mitochondrial DNA in trisomy 21. Three years later she presented a paper at the 6th world Congress on Down syndrome in Madrid, dealing with “why is it necessary to study the role of the mitochondrial genome in Trisomy 21 pathogenesis”. Subsequent studies showed that multiple genes affecting mitochondria are located on chromosome 21. A decreased level of ATPase (a mitochondrial DNA

product) has also been documented in Down syndrome patients. So, there have been both nuclear and mitochondrial genes identified as abnormal. This data suggests that oocyte mitochondrial dysfunction is involved in the pathogenesis of the chromosomal non-disjunction in the syndrome. Mitochondrial dysfunction has also been implicated in heterotaxy and defective migration of embryonic cells in Down syndrome. This is because normal ATPase generation is required for those processes. In this regard, it’s notable that trisomy 18, trisomy 13, and Klinefelter syndrome patients also have been reported as having abnormal mitochondrial function, cellular oxidative stress and or anomalies of the mitochondrial genome. This is all consistent with oocyte mitochondrial dysfunction being a causative factor in several conditions in which nondisjunction is present. Mitochondrial function generally worsens with advancing age. This helps to explain why non-disjunction is more common in older mothers. Mitochondrial dysfunction has also been implicated in autism spectrum disorder, fragile X syndrome and fetal alcohol spectrum disorders (alcohol is a mitochondrial toxin).

Mitochondrial medicine and the understanding of normal and pathologic mitochondrial anatomy and physiology is at the cutting edge of modern medicine. It will only become more important in the future. Of significance here is the fact that at least some mitochondrial disorders are treatable with agents such as ubiquinol, carnitine, and alpha lipoic acid. Down syndrome now presents the option of being treatable. In the January 2023 issue of “Mitochondrion”, Ganguly and Kadam wrote that “a

number of pharmacologically active natural compounds such as polyphenols, antioxidants, and flavonoids show convincing outcomes for reversal of the dysfunctional mitochondrial network and oxidative metabolism and improvement of intellectual skills in mouse models of Down syndrome and humans with Down syndrome”. In another 2023 article, Tan et al commented that “it is prudent that improving Down syndrome pathophysiologic conditions or quality of life may be feasible by targeting something as simple as mitochondrial biogenesis and function”. Fatty acid supplements seem to be beneficial in the mouse model of Down syndrome. One case study showed that fish oil rich in omega 3 fatty acids reversed mitochondrial dysfunction and was well tolerated in a Down syndrome child. Another group has reported modest improvement in coordination and muscle function in Down syndrome children treated with ubiquinol (Co-enzyme Q). Agents that have caused a dramatic improvement and even reversal of mitochondrial network abnormalities and abnormal bioenergetics include metformin, pioglitazone, reservatrol and EGCG (epigallocatochin 3 gallate). Those studies were done with in vitro cultures of Down syndrome cells. Metformin is an especially exciting therapeutic option since it has a long history of use, multiple other indications, an acceptable safety profile, crosses the blood brain barrier, and has been used in children. The in vitro benefits of metformin are impressive. In their paper on metformin treatment, Izzo et al concluded that “metformin represents a promising strategy to counteract mitochondrial dysfunction in Down

Continued on Page 18

syndrome”. Currently, the University of California is conducting a metformin study to treat fragile X syndrome and its’ associated obesity. There are also multiple trials using metformin regarding longevity and aging. Presently, however, there are no therapeutic trials available in the U.S.A. involving either metformin or pioglitazone in Down syndrome. A recent internet search showed that there are also no American controlled trials using flavanoids, fatty acids, polyphenols, or ubiquinol. This is difficult to comprehend given the fact that for over a decade there has been a lot of convincing evidence that Down syndrome is a mitochondrial disease that in vitro responds well to these agents.

An internet survey of several Down syndrome clinics in the Eastern United States at major medical centers showed no mention of mitochondrial dysfunction or mitochondrial treatment on their web sites. Most of these clinics did offer the option of genetic counselling and prenatal diagnosis. Prenatal diagnosis affords the option of abortion as a “treatment”. Early stimulation programs and learning therapies were generally offered by all the clinics. In the absence of controlled trials, should Down syndrome patients be afforded the option of “off label” structured empiric treatment with metformin? This might be particularly advantageous because of the safety profile plus the added benefit of metformin in obese pre-diabetic patients (a common problem with Down syndrome). Given the potential benefits, it would seem justified that metformin be offered as an empiric option. The possibility of offering a structured trial of the other agents with in vitro

effectiveness should also be considered especially in regard to supplements of ubiquinol and fatty acids which have minimal side effects. Additionally Down syndrome patients should prudently avoid known mitochondrial toxins including alcohol, valproic acid, chloramphemicol, gentamycin, and tobramycin. It is possible that other antibiotics could also be hazardous in Down syndrome given the fact the mitochondria likely evolved from primitive bacteria. The potential for Down syndrome to be a treatable medical condition should have been received with enthusiasm and excitement. This has not been the case. Perhaps this is due to the fact that major pediatric journals have neglected this topic. This may also be due in part to certain physician attitudes regarding Down syndrome and people with cognitive dysfunction. Studies have documented that a significant percentage (as much as 24%) of practicing physicians and resident physicians are “not comfortable” caring for people with Down syndrome. It is hoped that this article may help a bit in making morephysicians aware of this literature and the available treatment options.

MITOCHONDRIAL DISEASE IN DOWN SYNDROME REFERENCES

Craven et al, 2017. “Recent Advances in Mitochondrial Disease”, The Annual Review of Genomics and Human Genetics. 18:257-275.

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Valenti et al, 2017. “Inhibition of Drp1 Mediated Mitochondrial Fission Improves Mitochondrial Dynamics and Bioenergetics Stimulating Neurogenesis in Hippocampal Progenitor Cells From a Down’s Syndrome Mouse Model”, Biochim Biophys Acta Mol Basis Dis.2017 Dec 1863(12):3117-3127.

Valenti et al, 2021. “Impaired Brain Mitochondrial Bioenergetics in the Ts65Dn Mouse Model of Down Syndrome is Restored by Neonatal Treatment with the Polyphenol 7,8-Dihydroxy flavone”, Antioxidants, 2021 Dec 28; 11(1):62.

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Bayona-Bafaluy et al, 2021. “Down Syndrome is an Oxidative Phosphorylation Disorder”, Redox Biology 41(2021) 101871.

Dierssen et al, 2020. “Down Syndrome is a Metabolic Disease: Altered Insulin Signaling Mediates Peripheral and Brain Dysfunctions”, Frontiers in Neuroscience July 2020, vol 14, article 670.

Helguera et al, 2013. “Adaptive Downregulation of Mitochondrial Function in Down Syndrome”, Cell Metabolism 2013 January 8:17(1):132-140.

Pecze et al, 2020. “Meta-Analysis of Metabolites Involved in Bioenergetic Pathways Reveals a Pseudohypoxic State in Down Syndrome”, Mol Med. 2020 Nov 9;26(1):102.

Nowinski et al, 2020. “Mitochondrial Fatty Acid Synthesis Coordinates Oxidative Metabolism in Mammalian Mitochondria”, Elife 2020 Aug 17;9:e58041.

Anderson et al, 2021. “Trisomy 21 Results in Modest Impacts on Mitochondrial Function and Central Carbon Metabolism”, Free Radic Bio. Med. 2021 Aug. 20;172:201-212.

Busciglio et al, 2002. “Altered Metabolism of the Amyloid Beta Precursor Protein is Associated With Mitochondrial Dysfunction in Down’s Syndrome”, Neuron Feb 28;33(5):677-88.

D’Acunzo et al, 2021. “Mitovesicles are a Novel Population of Extracellular Vesicles of Mitochondrial Origin in Down Syndrome”, Sci Adv. 2021 Feb 12;7(7):eabe5085.

Zamponi et al, 2019. “The Shape of Mitochondrial Dysfunction in Down Syndrome”, Dev. Neurobiol. 2019 Jul;79(7):613-621.

Piccoli et al, 2012. “Chronic ProOxidative State and Mitochondrial

Dysfunctions are More Pronounced in Fibroblasts from Down Syndrome Foeti with Congenital Heart Defects”, Hum Mol Genet. 2013 Mar 15;22(6):1218-32.

Conti et al, 2001, Altered Expression of Mitochondrial and Extracellular Matrix Genes in the Heart of Human Fetuses with Chromosome 21 Trisomy, BMC Genomics 2007 Aug 7;8:26

Hefti et al, 2014. “Analysis of mtDNA, miR-155 and BACH1 Expression in Hearts from Donors With and Without Down Syndrome”, Mitochondrial DNA A DNA Mapp Seq Anal 2016; 27(2):896-903.

Hefti et al, 2017. “Analysis of Heteroplasmic Variants in the Cardiac Mitochondrial Genome of Individuals with Down Syndrome”, Human Mutat. 2017 Jan; 38(1):48-54.

Venegas-Zamora et al, 2022. “New Molecular and Organelle Alterations Linked to Down Syndrome Heart Disease”, Front Genet. 2022 Jan 18;12:792231.

Phillips et al, 2013. “Defective Mitochondrial Function in Vivo in Skeletal Muscle in Adults With Down’s Syndrome: a 31P-MRS Study”, Plos One, 2013 Dec 31;8(12).

Roat et al, 2007. “Mitochondrial Alterations and Tendency to Apoptosis in Peripheral Blood Cells from Children with Down Syndrome”, FEBS Lett, 2007 Feb 6;581(3):521-5.

Perluigi et al, 2012. “Oxidative Stress and Down Syndrome: A Route Toward Alzheimer-Like Dementia”, Curr Gerontol Geriatr Res. 2012;2012: 724904.

Valenti et al, 2014. “Mitochondrial Dysfunction as a Central Actor in Intellectual Disability-Related Diseases: An Overview of Down Syndrome, Autism, Fragile X and Rett Syndrome” Neuroscience Biobehav Rev. 2014 Oct;46 Pt 2:202-17.

Kim et al, 2000. “Decreased Level s of Complex III Core Protein 1 and Complex V beta Chain in Brains from Patients with Alzheimer’s Disease and Down Syndrome”, Cell Mol Life Sci. 2000 Nov; 57(12):1810-6.

Kim et al, 2001. “Decreased Protein Levels of Complex I 30-kDa Subunit in Fetal Down Syndrome Brains”, Neuro Transm Suppl. 2001;(61):109-16.

Kim et al, 2001. “The Reduction of NADH Ubiquinone Oxidoreductase 24- and 75-kDa Subunits in Brains of Patients with Down syndrome and Alzheimer’s Disease”, Life Sci. 2001 May 4 68(24):2741-50.

Mollo et al, 2021. “Human Trisomic iPSCs from Down Syndrome Fibroblasts Manifest Mitochondrial Alterations Early During Neuronal Differentiation”, Biology 2021, 10, 609.

Arbuzova, Svetlana, 1998, “Why it is Necessary to Study the Role of the Mitochondrial Genome in Trisomy 21 Pathogenesis”, Down Syndrome Research and Practice, 5(3), 126-130

Schon et al, 2000. “Chromosomal Non-disjunction in Human Oocytes: is there a Mitochondrial Connection?”, Human Reproduction vol. 15 (suppl.2) pp. 160-172.

Lee et al, 2003. “Expression of the Mitochondrial ATPase6 Gene and Tfam in Down syndrome”, Mol Cells. 2003 April 30;15(2):181-5.

Helguera et al, 2005. “ETS2 Promotes the Activation of a Mitochondrial Death Pathway in Down Syndrome Neurons”, J. Neurosci. 2005 Mar 2;25(9):2295-303.

Parra et al, 2018. “Down Syndrome Critical Region 1 Gene, Rcan1, Helps Maintain a More fused Mitochondrial Network”, Circ. Res. 2018 Mar 16;122(6):e20-e33.

Burkhalter et al, 2019. “Imbalanced Mitochondrial Function Provokes Heterotaxy Via Aberrant Ciliogenesis”, J Clin Invest. 2019 Jul 1; 129(7):28412855.

Buczynska et al, 2022. “Future Perspectives in Oxidative Stress in Trisomy 13 and 18 Evaluation”, J. of Clinical Medicine 2022, 11,1787.

Oikawa et al, 2002. “The Specific Mitochondrial DNA Polymorphism Found in Klinefelter’s Syndrome”, Science Direct Vol 297, issue 2, 20 September 2002, pp. 341-345.

Siddiqui et al, 2016. “Mitochondrial Dysfunction in Autism Spectrum Disorders”, Autism Open Access.; 6(5): doi:10.4172/2165-7890.

Parikh et al, 2009. “A Modern Approach to the Treatment of Mitochondrial Disease”, Curr Treat Options Neurol. 2009 November; 11(6):414-430.

Valero, Teresa, 2014. “Mitochondrial Biogenesis: Pharmacological Approaches”, Curr Pharm Res 2014;20(35):5507-9.

Franceschi et al, 2018. “Accelerated Bio-cognitive Aging in Down Syndrome: State of the Art and Possible Deceleration Strategies”, Aging Cell. 2019;18:e12903.

Mollo et al, 2020. “Targeting Mitochondrial Network Architecture in Down Syndrome and Aging”, Int. J. of Molecular Sciences 2020,21, 3134.

Izzo et al, 2018. “Mitochondrial Dysfunction in Down Syndrome: Molecular Mechanisms and Therapeutic Targets”, Molecular Medicine (2018) 24(1):2.

Ganguly et al, 2023. “Therapeutics for Mitochondrial Dysfunction-linked Diseases in Down Syndrome”, Mitochondrion 2023 Jan;68:25-43.

Valenti et al, 2018. “Mitochondria as Pharmacological Targets in Down Syndrome”, Science Direct vol 114, Jan 2018, pp. 69-83.

Ganguly, Bani, 2022, “Disarrayed Mitochondrial Function and Pathobiology in Down Syndrome and Targeted Therapeutics”, Science Direct 2022, pp. 219-243.

Tan et al, 2023. “Mitochondrial Dysfunction in Down Syndrome: From Pathology to Therapy”, Neuroscience, vol 511, 10 February 2023, pp. 1-12.

Vacca et al, 2015. “Green Tea, EGCG, plus Fish Oil Omega-3 Dietary Supplements Rescue Mitochondrial Dysfunctions and are Safe in a Down Syndrome Child”, Clinical Nutrition volume 34, issue 4, August 2015, pp. 783-784.

Martinezcue et al, 2022. “Fatty Acids: A Safe Tool for Improving Neurodevelopmental Alterations in Down Syndrome?” Nutrients 2022 Jul 13;14(14):2880.

Valenti et al, 2016.The Polyphenols Resveratrol and Epigallocatechin-3gallate Restore the Severe Impairment in Hippocampal Progenitor Cells from a Down Syndrome Mouse Model”, Biochim Biophys Acta. 2016 Jun;1862(6):1093-104.

Valenti et al, 2013. “Epigallocatechin3-gallate Prevents Oxidative Phosphorylation Deficit and Promotes Mitochondrial Biogenesis in Human Cells from Subjects with Down’s Syndrome”, Biochim Biophys Acta 2013 Apr, 1832(4):542-552.

Mollo et al, 2019. “Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells”, Frontiers in Medicine June 2019, vol. 10, article 606.

Izzo et al, 2017. “Metformin Restores the Mitochondrial Network and Reverses Mitochondrial Dysfunction in Down Syndrome Cells”, Human Mol. Genet. 2017, vol 26, no.6:1056-69.

Lagouge et al, 2006. “Resveratrol Improves Mitochondrial Function and Protects Against Metabolic Disease by Activating SIRT1 and PGC-1”, Cell 127, 1109-1122, Dec 15 2006.

Neergheen et al, 2017. “Coenzyme Q10 in the Treatment of Mitochondrial Disease”, Journal of Inborn Errors of Metabolism 2017, vol 5:1-8.

Quinzii et al, 2019. “Coenzyme Q and Mitochondrial Disease”, https:// www.ncbi.nim.nih.gov/ pmc/articles/ PMC3097389/.

Lagos Tara et al 2022, I Am Not The Doctor For You: Physicians Attitudes About Caring for People With Disabilities, Disability and Health, vol. 41, no. 10

Pace Jill et al 2011, Understanding Physician’s Attitudes Toward People With Down Syndrome, Am J Med Genet Jun;155A(6): 1258-1263

Hannah F. et al 2023, Education Research: Predictors of Resident Physician Comfort With Individuals With Intellectual and Developmental Disabilities, Neurology Education 2-e 2000045 doi: 10.1212

The opinion expressed in this column is that of the writer and does not necessarily reflect the opinion of the Editorial Board, the Bulletin, or the Allegheny County Medical Society.

The American College of Surgeons – Southwestern Pennsylvania Chapter is excited to host its annual “Most Interesting Case Presentations” event. This event provides surgical residents the opportunity to present their most interesting cases for review and discussion. Presentations are judged by a panel of surgeons. Cash prizes are awarded to the three most interesting cases.

AGENDA

6:00 PM

EXECUTIVE BOARD MEETING (Invite Only)

6:30 PM – 7:00 PM

COCKTAILS

7:00 PM – 8:00 PM

PRESENTATIONS & DINNER

AWARDS

1ST PLACE - $500

2ND PLACE - $300

3RD PLACE - $200

OPEN TO ALL GENERAL SURGERY RESIDENTS AND SURGICAL SPECIALTY RESIDENTS.

SAVE THE DATE!

Registration coming soon.

Featured Grant Recipient

Family House

Family House opened on November 13, 1983 with a mission to provide a safe, comforting, and affordable “home away from home ” for patients and their families who travel to Pittsburgh hospitals for expert medical care. To fulfill its mission, Family House offers a room rate at a fraction of what one would pay for a hotel in the Oakland or Shadyside neighborhoods. The peaceful, home -like atmosphere at Family House has been intentionally designed, with complimentary services such as weekday breakfast, transportation, stocked food pantries, and more.

Family House is an essential partner in the region ’s healthcare delivery system, serving those who travel long distances, as well as Pennsylvania residents who must travel across the state. Family House’s lodging facility and the services, carried out by its professional staff and volunteer corps, are an essential part of the healthcare journey.

Everything Family House provides helps stretch financial resources for families in the midst of a medical situation. In FY21, Family House ’s room rates remained at deeply discounted levels, with 25% of room operating costs subsidized through philanthropic contributions. Family House met the lodging needs of 13,753 patients and caregivers over 8,235 reservations and 25,884 nights of service.

This impact is owed to each volunteer who prepares a home -cooked meal, every donor who mailed in a handwritten check, the corporations who invest in our annual fundraising efforts, and t the foundations who partner with us in making Pittsburgh hospitable for all.

To learn more about Family House visit: familyhouse.org

Donate to the ACMS Foundation to help support annual grant giving.

To learn more about the ACMS Foundation visit: acms.org/acmsfoundation

MISSION

Founded in 1960, the Allegheny County Medical Society Foundation has extended the reach of physicians into the community through grant giving to local organizations.

The mission of the Foundation is: A Advancing Wellness by confronting Social Determinants and Health Disparities. This mission works to fulfill an overall vision of a healthy and safe Allegheny County.

Throughout the ups and downs of the past few years, the Foundation’s work has become even more important in supporting local non-profit organizations.

The desire to give back to the community is an inherent trait of those who become physicians. In past year ’s the ACMS has hosted an annual gala to help raise funds to support the Foundation. Due to COVID-19, just like many other organizations, the ACMS had to forego the inperson gathering. While we look forward to hosting a Foundation fundraising event in the near future, the work of the Foundation continues on. Please consider how you can personally help support the Foundation and, in turn, continue to support a healthy region.

Contact the ACMS team to learn more about how your organization can help support the ACMS Foundation.

As physicians, you know that it takes a village to keep the community healthy and safe. Please consider a donation to the Allegheny County Medical Society Foundation.

Your donation will help the Foundation fund local non-profits in future grant cycles, and will help further the mission of the ACMS Foundation.

Donations can be mailed to: ACMS Foundation

850 Ridge Avenue Pittsburgh, PA 15212

Scan this QR Code to Donate via Qgiv:

ACMS Honors will Acknowledge Top Physicians Under 40 and Foundation Grant Recipients

Sara Hussey, ACMS Executive Director

The ACMS Foundation is excited to announce several of our honorees for the 2023 ACMS Honors Event that will be held on Thursday, April 27 at the Heinz History Center. As we bring back the signature social event of the year for ACMS Members (formerly known as the ACMS Foundation Gala), we will be offering an abbreviated version of the traditional ACMS Awards. We look forward to bringing back a full slate of award acknowledgements in 2024.

The Pennsylvania Medical Society Top Physicians Under 40 award is awarded to physicians throughout the commonwealth who are talented early career physicians, who already are performing at a high level. Pennsylvania’s Top Physicians Under 40 recognizes on a yearly basis the best of the best early career physicians. At the 2023 ACMS Honors Event, award recipients from 2022 and 2023 will be acknowledged.

2022 Winners include: Phillip Adams, DO; Michael Aziz, MD; Michael Best MD; Karen Bucher, MD; Tajh Ferguson, MD; Natalie Gentile, MD; James Miller, MD; Thomas Radomski, MD; Lauren Rossman, DO; and Lindsay Turner, MD. 2023 Award Winners are set to be publicly announced the first week in April and we look forward to acknowledging those winners in the April Bulletin.

The ACMS Honors event will also feature three of the organizations who were 2022 ACMS Foundation Grant Award Recipients. Leaders from Beverly’s Birthdays, Family House, and Jeremiah’s Place will share how the Foundation Grants have had an impact on their organizations.

If you have not registered for ACMS Honors, the deadline to register is April 15. Tickets are $100 and include dinner stations, open bar, valet, and access to the Sports Exhibit. We are also offering a “Circle of Friends” ticket. This $500 contribution includes two tickets to the event, acknowledgement in the program and on the ACMS website, and acknowledgement in the 2023 Annual Report. The tax-deductible portion of the event is $300.00.

https://alleghenycountymedicalsociety.regfox.com/acms-honors

2022 PAMED Top Physicians Under 40 Winners from Allegheny County

ACMS News

Allegheny County Medical Society Alliance Annual Holiday Luncheon

South Hills Country Club was the festive scene for Allegheny County Medical Society Alliance Annual Holiday Luncheon and Celebration on Saturday December 3, 2022. Patty Barnett, event chairperson, along with her committee, Tina Purpura, Sandra DaCosta and Barbara Wible, planned a memorable and charitable event. Members and their guests gathered to celebrate continued friendship, forged over several decades, to support the Alliance’s philanthropic mission. Raffles and door prizes, headed by Tina Purpura, put the FUN in FUNdraising. Barbara Wible made club arrangements. The featured entertainer was vocalist John Sarkis.

This year’s chosen recipient was Operation Safety Net, a program headed by Dr. Jim Withers at Mercy Hospital. Five hundred dollars was pledged to this valuable program that aids in clothing the homeless in the greater Pittsburgh area. Hats and socks were also collected to donate to those in need. A check for $500 was presented by Patty Barnett at Mercy Hospital to Dr. Withers and his “street medicine fellow” Dr. Eddy Egan.

Sharon Wible Mankovich, Betsy Southern

Barbara Wible, Kathleen Reshmi, Patty Barnett, Sandra DaCosta, Kathleen Lee, Tina Purpura, Liz Blume

Kathleen Lee, Charlie Blume, Liz Blume

Patty Barnett, Sandra DaCosta, Tina Purpura

Dr. Alan Barnett, Patty Barnett, Kathleen Lee

Patty Barnett, musician John Sarkis, Tina Purpura

Patty Barnett, Santa, Tina Purpura

Patty Barnett presents check to Dr. Jim Withers for Operation Safety Net

Mercy Street Medicine fellow Dr. Eddy Egan, Patty Barnett, Operation Safety Net Dr. Jim Withers

Dr. Alan Barnett, Dr. Larry Purpura, Charlie Blume

Daprodustat: The First Oral Agent for the Treatment of Anemia in Chronic Kidney Disease

Background

Chronic Kidney Disease

About 15% of adults in the United States (US) are estimated to have chronic kidney disease (CKD).1 When patients first develop CKD, they may be asymptomatic. However, the progressive nature of CKD leads patients to experience a decreased quality of life over months to years. Patients with CKD are at a higher risk for acute kidney injury (AKI), uremia, cardiovascular disease, drug toxicities, and many other complications.2 Due to the number of health consequences associated with CKD, it remains the leading cause of death in the US.1 Because most causes of CKD are irreversible, the goals of therapy are to slow the progression to renal failure. Once the kidneys start failing and patients are diagnosed with end-stage renal disease (ESRD), treatment options are limited to hemodialysis (HD) or transplantation. At this point in the course of CKD, patients most likely have developed the aforementioned complications and other common conditions such as anemia.2

Anemia of Renal Disease

Clinical trials have shown as the glomerular filtration rate (GFR) decreases, patients with CKD have a gradual decline in hemoglobin (Hb) concentration.2 The cause of this is most commonly due to a lack of endogenous erythropoietin (EPO) production due to impaired kidney function. However, nutritional deficiencies and blood loss due to dialysis may contribute.3 Because this is a common

occurrence in those with CKD and is associated with increased morbidity and mortality, the 2012 KDIGO guidelines suggest monitoring all patients with CKD for anemia. The most common symptoms are fatigue, reduced exercise tolerance, and dyspnea. Diagnosis is made by obtaining a complete blood count (CBC), absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate levels. Patients are deemed anemic if they have a Hb concentration of <13 g/dL in males or <12 g/dL in females. For patients with adequate nutritional stores or who remain anemic despite supplementation, erythropoietin-stimulating agents (ESA) such as epoetin alfa and darbepoetin are used. Clinical trials have shown the benefit of treatment with ESAs for those on dialysis by controlling anemia and reducing the need for blood transfusions.4 However, ESAs are administered subcutaneously (SQ) or intravenously (IV), which is unattractive to some patients who prefer oral therapy. After nearly 35 years of parenteral ESAs being the only option for these patients, an oral option is now available.

Daprodustat (Jesduvroq)

In June 2020, daprodustat (Jesduvroq), manufactured by GlaxoSmithKline, was approved in Japan for the treatment of anemia in patients with CKD. Daprodustat is an oral small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (PHD) which prevents the degradation of hypoxia-inducible factor (HIF). HIF promotes endogenous EPO

production, which is often the cause of anemia in CKD. Two phase 3 trials in Japan assessed the use of daprodustat in hemodialysis patients. One trial focused on initiating daprodustat in those not using an ESA, while the other compared daprodustat to darbepoetin alfa. Another phase 3 trial in Japan assessed daprodustat use in non-HD dependent patients (ESA naïve and ESA users). All three trials assessed Hb concentrations as the primary outcome and determined that daprodustat was effective and non-inferior to ESAs for treating anemia in CKD. Additionally, no significant differences in terms of safety were determined.5 Because of the success of daprodustat in Japan, international trials have been performed. The results of these trials subsequently led to FDA approval of daprodustat on February 2, 2023, for treating anemia due to CKD in adults who have been receiving dialysis for at least four months.6

Daprodustat Clinical Trials

Anemia Due to Chronic Kidney Disease in Adults on Dialysis

Used as the basis of FDA approval, the Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat–Dialysis (ASCEND-D) trial assessed the safety and efficacy of daprodustat. The ASCEND-D trial was a randomized, open-label, phase 3 trial that included 2964 patients across 431 centers in 35 countries. To be included in the trial, CKD patients had to have been undergoing dialysis for at least 90 days, had received

maley Zents, PhaRmD CanDiDate, leCOm sChOOl OF PhaRmaCy anD tuCKeR FReeDy, PhaRmD, BCPs

Materia Medica

an ESA for at least six weeks, and had a Hb level between 8-12 g/dL. Additionally, patients had to have adequate iron stores and serum transferrin saturation. The main exclusion criteria included anemia unrelated to CKD, a recent cardiovascular event, or current or recent cancer. Patients were randomized to either oral daprodustat or an injectable ESA (IV epoetin alfa or SQ darbepoetin alfa) groups. Initial doses of daprodustat (4-12 mg) were chosen based on the patient’s previous ESA dose and were adjusted anywhere from 1-24 mg as needed to maintain a Hb range of 10-11 g/dL. The participants were evaluated at least every four weeks for the first year and every 12 weeks thereafter from November 23, 2016, to August 10, 2018. Two primary noninferiority outcomes were assessed and included the

mean change in the Hb level from baseline to the average, during weeks 28-52, and the first occurrence of a major cardiovascular event (MACE). Additionally, secondary outcomes included the average monthly dose of IV iron (baseline through week 52), the first occurrence of a MACE, the first occurrence of a MACE or thromboembolic event, and the first occurrence of a MACE or hospitalization for heart failure. All three cardiovascular secondary outcomes were tested for superiority rather than noninferiority.7

The primary outcomes results of the trial are summarized in the figure below. Both primary outcomes met noninferiority criteria, concluding that oral daprodustat was non-inferior to parenteral ESAs in terms of change in Hb concentration from baseline and occurrences of MACEs.7

As for secondary outcomes, none of the cardiovascular outcomes were significantly different between groups: the first occurrence of MACE (hazard ratio, 0.93; 95% CI, 0.811.07), the first occurrence of MACE or a thromboembolic event (hazard ratio, 0.88; 95% CI, 0.78-1.00), the first occurrence of MACE or hospitalization for heart failure (hazard ratio, 0.97; 95% CI, 0.85-1.11). The difference in mean monthly dose of IV iron was also insignificant and showed a decrease of 90.8±3.3 mg in the daprodustat group and 99.9±3.3 mg in the ESA group, for a mean difference of −9.1 mg (95% CI, −18.4 to 0.2 mg). Additionally, no significant differences were found when comparing adverse events between the daprodustat and ESA groups.7

Daprodustat Prescribing Information

Indication and Administration

Daprodustat is approved in the US for anemia due to CKD in adults who have been on dialysis for at least four months. Daprodustat is a once-daily oral tablet taken without regard to food, iron, phosphate binders, or dialysis. Iron status should be monitored during daprodustat therapy and supplemental iron should be administered when serum ferritin is <100 mcg/ mL and/or when serum transferrin saturation is <20%. Liver function tests should be assessed before treatment and if there are concerns for liver disease during treatment. 6

Continued on Page 30

Materia Medica

Dosing

Daprodustat dosing should be individualized so patients are on the lowest dose to reduce the need for red blood cell transfusions. As with ESAs, doses should not be used to target a Hb concentration greater than 11 g/dL. Starting doses of daprodustat are found in the tables below, differing between patients not on ESA therapy and those who are.6

Starting Dose for Adults not Receiving an ESA

Contraindications, Warnings, and Adverse Reactions

Starting Dose for Adults Switching from an ESA

The use of daprodustat is contraindicated in those taking strong CYP2C8 inhibitors or who have uncontrolled hypertension. Providers should avoid using daprodustat in those who have had a myocardial infarction, cerebrovascular event, or acute coronary syndrome within the three months before consideration of therapy.6 Most common adverse reactions reported in the ASCEND-D trial were hypertension (16%), diarrhea (11%), and headache (8%). Some patients experienced other serious effects such as hospitalization due to heart failure (28.6%), gastrointestinal erosions (4.0%), and malignancy (3.2%). Although there are serious risks associated with daprodustat, they are similar to the risks of using ESAs. Additionally, as previously mentioned, the ASCEND-D trial showed no significant difference between daprodustat and ESAs in terms of safety data.7

Drug Interactions

of 24 mg once daily. Doses should be adjusted for patients with moderate hepatic impairment (Child-Pugh Class B) and those taking moderate CYP2C8 inhibitors. For moderate hepatic impairment, starting doses should be reduced by half unless the starting dose is 1 mg. Use is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). For patients taking clopidogrel or moderate CYP2C8 inhibitors, starting doses should also be reduced by half, except in those whose starting dose is 1 mg.6

Monitoring

After initiation and each dose adjustment, monitor Hb every two weeks for the first month and every four weeks after. If adjusting a dose, increase or decrease by one dose level at a time. If a clinically meaningful increase in Hb is not achieved by week 24 of therapy, daprodustat should be discontinued. Recommendations for dose adjustments based on Hb levels are below.6

Daprodustat is metabolized through the CYP2C8 pathway and should not be used with strong CYP2C8 inhibitors due to a significant increase in daprodustat exposure. For moderate CYP2C8 inhibitors, daprodustat doses should be reduced as specified in the dosing instructions. Patients receiving CYP2C8 inducers along with daprodustat should have their Hb levels monitored, and the daprodustat dose should be adjusted when the CYP2C8 inducer is initiated or discontinued.6

Special Populations

There is a lack of data surrounding the use of daprodustat in pregnancy, lactation, and pediatrics. However, due to the presence of daprodustat in the milk of lactating rats, patients should not breastfeed during therapy and one week after discontinuation. As for geriatrics, 43% of participants treated in the ASCEND-D trial were aged 65 years and older. Evaluation • Restart at one dose level lower when Hb falls within target range

Materia Medica

of the data did not present any differences in both safety and efficacy between these patients or the younger patients in the trial.6

Future Implications and Conclusion

Although only approved in the US for once-daily dosing for anemia of CKD in adults undergoing dialysis, other clinical trials with daprodustat have been conducted. Daprodustat has been studied and approved in Japan for anemia in patients with CKD not undergoing dialysis. The data has shown noninferiority to darbepoetin alfa for change in the Hb concentration from baseline and cardiovascular outcomes. The lack of approval for this indication is likely attributed to the higher frequency of some adverse events (cancer-related death and tumor progression/ recurrence) in patients taking daprodustat and that no other ESAs were used as comparators.8 Also, the ASCEND-D trial was extended to compare daprodustat three times weekly dosing of daprodustat to epoetin alfa, which showed noninferiority for the mean change in Hb concentration. However, the trial did not have adequate power to test cardiovascular endpoints and lacked comparison to ESAs other than epoetin alfa.9

Anemia is one of the most common complications associated with CKD. When other causes, such as nutrient deficiencies, are ruled out, anemia in these patients is likely due to kidney damage resulting in decreased EPO production. For the past 35 years, these patients have had limited options for treatment, all of which have been parenteral agents. As of February 2, 2023, there is an oral agent available. Daprodustat is the first oral agent FDA approved for adults with anemia who have been undergoing dialysis for at least four months. Data from an international trial with 2,964 participants showed that daprodustat was non-inferior to ESAs regarding the

change in Hb concentration from baseline and occurrences of MACEs. Also, adverse reactions and risks associated with daprodustat were not significantly different than the comparator agents in the trial.6 Due to recent approval, daprodustat is not yet available for purchase. Additionally, GlaxoSmithKline has not released pricing or insurance coverage information.

References

1. Chronic Kidney Disease Basics. Centers for Disease Control and Prevention. https://www. cdc. gov/kidneydisease/basics.html#:~:text=disease%20(CKD).-,About%20Chronic%20Kidney%20 Disease,as%20heart%20disease%20 and%20stroke. Published February 28, 2022. Accessed February 21, 2023.

2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):1-150. doi: 10.1038/ kisup.2012.73.

3. Anemia in Chronic Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/kidney%20disease/anemia#:~:text=of%2 0renal%20disease.-,How%20common%20 is%20anemia%20in%20CKD%3F,with%20 kidney% 20disease%20have%20anemia. Published September 2020. Accessed February 21, 2023.

4. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl. 2012;2(4):279-335. doi: 10.1038/kisup.2012.32.

5. Dhillon S. Daprodustat: First Approval. Drugs. 2020;80(14):1491-1497. doi:10.1007/s40265020-01384-y

6. Jesduvroq [package insert]. Durham, NC: GlaxoSmithKline. https://gskpro.com/content/ dam/glob al/hcpportal/en_US/Prescribing_Information/Jesduvroq/pdf/JESDUVROQ-PI-MG. PDF. Publish ed February 2023. Accessed February 21, 2023.

7. Singh AK, Carroll K, Perkovic V, et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021;385(25):2325-2335. doi:10.1056/nejmoa2113379

8. Singh AK, Carroll K, McMurray JJV, et al. Daprodustat for the Treatment of Anemia in Patients not Undergoing Dialysis. N Engl J Med. 2021;385(25):2313-2324. doi:10.1056/ nejmoa2113380

9. Coyne DW, Singh AK, Lopes RD, et al. Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients. Clin J Am Soc Nephrol. 2022;17(9):1325-1336. doi:10.2215/ cjn.00550122

Ms. Zents is a Doctor of Pharmacy candidate at LECOM School of Pharmacy. Dr. Freedy is a Clinical Pharmacy Specialist in Medicine and Drug Information at Allegheny Health Network, Allegheny General Hospital. For any questions concerning this article, please contact Dr. Freedy at the Allegheny Health Network, Allegheny General Hospital, Center for Pharmaceutical Care, Pittsburgh, PA. (412) 359-3192 or email tucker.freedy@ahn.org

The Benefits of Pre-litigation Mediation

By lOuRDes sanCheZ RiDGe

Today, health care systems and its participants are constantly embroiled in conflict and the threat of litigation. A fast and inexpensive tool a provider can engage in prior to litigation is mediation. Whether it is a patient who is dissatisfied with a provider’s services, a disgruntled employee who complains about working conditions, or a physician who distrusts his/her business partner, health care professionals spend an inordinate amount of time, energy and money in attempting to resolve disputes. Once a complainant files legal action, the expenses of litigation climb substantially. Depending on the claim filed, certain statutes award the complainant (the “plaintiff”) attorney’s fees if he/she succeeds. As a result, not only is the provider paying for his/ her own attorney’s fees, he/she is also paying for the plaintiff’s litigation expenses. Keep in mind, that it is to the economic benefit of the plaintiff’s attorney to continue the litigation as long as possible in order to maximize his/her fees.

Mediation is an informal process where the parties select a mediator to facilitate a discussion with the purpose of reaching an agreement. The decision to reach an agreement lies solely with the parties and not the mediator. Mediators do not decide the outcome or casts blame. They facilitate the discussion where each party’s interests are clearly defined and guides the parties into resolving their differences. They help parties evaluate new options and aid in tailoring a solution that meets both parties’ needs. Because mediators are a neutral third party, direct confrontations between the parties are avoided.

Many of the root causes of litigation is a lack of communication and understanding. If a complaint or problem is not addressed promptly, effectively and compassionately, the complainant feels unheard and betrayed by the health care provider.

When a patient or family member feels ignored or not listened to, they become angry. They blame the doctor for their illness and question the doctor’s competence because they do not understand the medical process. This can lead to a medical malpractice claim or a complaint to the Pennsylvania Department of State or other governing organization. Many times, what the patient or family really needs is a chance to air their feelings and be provided with information. They need to feel valued and heard. Unfortunately, due to a myriad of factors, health care providers may not have the time or opportunity to

provide patients and family members with the attention or information they need. There are also difficult patients and family members whom health care providers may want to avoid. If a health care provider finds that an issue is percolating and the patient or family member becomes increasingly agitated, the provider should consider using an unbiased mediator to facilitate a discussion between the parties to resolve the conflict before the patient or family member escalates the problem. Similarly, when staff become disenchanted or express feelings of discrimination, sexual harassment or unfair treatment, there is a great potential that those feelings will lead to litigation. Litigation in the employment arena can be very expensive due to several statutes that awards the plaintiff attorneys fees.

Over 90% of civil cases never see a jury because they settle before trial. Although discovering the opponent’s case and obtaining favorable decisions from motions filed may be advantageous when settling a case, the majority of the funds spent on prolonging the conclusion of a case will most often not be justified.

All civil actions filed in federal court and state court in the Western Pennsylvania require the parties to participate in an Alternative Dispute Resolution (“ADR”) process. The most frequently used ADR methods are mediation, arbitration and early neutral evaluation. In arbitration, both parties select one or more arbitrators who will decide the dispute. The arbitrator’s

Legal Summary

decision is binding and enforceable in a court of law. The arbitrator’s decision is confidential, discovery is limited, and the process is faster and less expensive than traditional litigation. The third most frequently used form of ADR is Early Neutral Evaluation (“ENE”). At an ENE, the parties also select the evaluator who will provide an unbiased assessment of the strengths and weaknesses of each party’s position. This process helps each party evaluate their chances of success at trial which usually leads to a settlement agreement. Many times, parties chose to engage in early neutral evaluation and end up engaging in mediation or vice-versa.

Litigation disrupts a health care provider’s work and everyday life. It adds an additional stress to an already stressful career. Engaging in pre-litigation mediation avoids the risk of high jury awards, maintains the complaint confidential, preserves the health care provider’s hard-earned reputation, substantially reduces litigation expenses and minimizes the disruption caused by litigation.

DISCLAIMER: This article is for information only and should not be considered legal advice. To obtain legal advice on this matter, please contact an attorney experienced in this area of law.

Lourdes Sanchez Ridge is a mediator and practices law at Pietragallo Gordon Alfano Bosick & Raspanti LLP. She is licensed in Pennsylvania, Washington, D.C. and Florida. Her bio can be found at https://www.pietragallo.com/lawyers.

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ALLEGHENY COUNTY MEDICAL SOCIETY IN THE PRESS

adjacent lumbar vertebra, explaining her pain. My resident, from Georgia, upon seeing the findings said, in his deep southern drawl, “Fellahs, there’s a lesson here. Crocks daah (die), too.” Unfortunately for the patient, CT scanning and ultrasound exams had not been developed. The important lesson is that for most patients with a diagnosis of psychosomatic illness, the symptoms are real, and in fact a small number of these patients indeed have real abnormalities accounting for their symptoms.

Sigmund Freud’s view of humor was that it was a conscious expression of thoughts that society usually suppressed or was forbidden.2 As long as the humor, in this case name-

calling, is meant in a benign fashion, it is considered harmless.

However, in today’s politically divisive atmosphere, it is best to use humor only when you truly know your audience. As a good example, I remember the not so “good old days,” when it was expected that a speaker at a conference or a refresher course would tell jokes. Many of the “old timers” were very colorful characters. Today, fortunately, speakers are business-like and jokes are tacitly forbidden, since they are bound to offend someone. Finally, we should always remember that no matter how unpleasant some of our patients are to us, they are still our fellow human beings.

Dr. Daffner, associate editor of the ACMS Bulletin, is a retired radiologist who practiced at Allegheny General

He is emeritus clinical professor of Radiology at Temple University School of Medicine and is the author of nine

• Physician Billing Services for All Specialties

We would use OUR billing system or YOUR billing system based on YOUR preference.

• Credentialing Services for All Specialties

• Accounts Receivable Follow-Up for Practice Support

We would work your accounts on your system to maximize cash flow.

NEW Billing Client Example: A new client (a 6-physician family medicine group) liked their EHR, so the group asked us to bill using their billing system. Besides the benefit of keeping their EHR, the group is now experiencing greater efficiency and stability in their office by eliminating problems caused by biller turnover, vacations, diversion, and other time off.

Contact Ruby Marcocelli, Vice President at 412-788-8007 or rmarcocelli@fennercorp.com

The opinion expressed in this column is that of the writer and does not necessarily reflect the opinion

2. Freud S, (Strachey J, Trans.). Jokes and their relation to the unconscious New York: W. W. Norton, 1960 (Original work published 1905).

Lessons from Babies with Trisomies

“The moral test of government is how it treats those who are in the dawn of life, the children; those who are in the twilight of life, the aged; and those in the shadows of life, the sick, the needy and the handicapped.”

March is Trisomy Awareness month.2 Most humans have twentythree pairs of chromosomes, one from each parent. When there are three rather than two of a specific chromosome, then there is a trisomy (From Latin and Greek, trisomy means “three bodies”). This month was selected because it is the third month of the year and the start of Spring. Trisomy Awareness Month not only sheds light on these diagnoses to educate both society and medical providers, but also to celebrate the children with these diagnoses.

Trisomies occur with any chromosome, but the clinical presentation is influenced by the specific chromosome found in triplicate. Some trisomies are embryonically lethal and cause very early pregnancy loss (such as trisomy 16 and trisomy 22). Other trisomies can present

with later pregnancy loss (including second or third trimester stillbirth) or fetal malformations detected by ultrasound. These trisomies include trisomy 21, trisomy 13 and trisomy 18. Prenatal diagnosis can be utilized to determine the chromosomal make-up of the fetus and establish the diagnosis of a trisomy. Prenatal diagnosis can be helpful in allowing more specific counseling for parents and to assist in making delivery and postnatal plans. Many babies with trisomies are born alive and go home with their parents, even the most complex diagnoses such as trisomy 18 and trisomy 13. Babies with trisomies typically have malformations, coexisting medical morbidities, and neurocognitive disability. The extent of each depends on the specific trisomy and the individual child.

As a reproductive geneticist, bioethicist, and perinatal palliative care expert, I have been fortunate to be involved in the care of babies with trisomies. I am moved and humbled by this aspect of my career, even daily. I have come to appreciate that caring for babies with trisomies – during pregnancy or after birth - has come with many lessons. As part of Trisomy Awareness Month, I would like to share several of these lessons with my medical community:

1. We need to practice evidencebased medicine with regards to babies with trisomies. More commonly, babies and children with trisomy 21 or Down syndrome receive evidence-based medical care. Although there continue to be significant barriers to accessing

adequate medical services for individuals with Down syndrome, there has been a paradigm shift within medicine. The origins of this shift can be traced back to several “Baby Doe” legal cases from the 1980’s.3 Specifically, the Baby Doe U.S. Supreme Court case from 1982 (in addition to other cases) involved a baby with Down syndrome with a tracheal-esophageal fistula that the physician chose not to intervene upon. The SCOTUS established that life-saving medical care could not be withheld from babies with disabilities or life-threatening conditions.4 In contrast to Down syndrome, in some regions of this country, babies with trisomy 18 and trisomy 13 may have care withheld or receive non-evidence-based medical care.5 Although mortality remains high among live newborns with these diagnoses, ongoing medical support and surgical repair of certain malformations, such as cardiac malformations, can significantly improve survival past one year of age for these babies.6 Therefore, the practice of routinely withholding care or without parental consent because the diagnosis is “universally lethal” should be questioned.

2. As health care providers, our words matter. Our language should be precise and based in medical facts.

Phrases such as “universally lethal”, “incompatible with life” or “severe disorder”, are often utilized when describing trisomy 13 and trisomy

1

Dr. Marta Kolthoff

From Page 38

18. These phrases are not only confusing but also misleading and not supported by the current medical evidence. Our choice of language can influence the care babies receive, especially babies with trisomy 13 and trisomy 18. Why would the care team provide medical support for a diagnosis that is “lethal” and has a “dismal prognosis”? Again, our words matter, not only to the parents and families but also the entire medical care team.

3. “Sometimes our opinions are disguised as facts.”10 If we are using non-evidencebased language, what are we truly communicating? We may be revealing our negative opinions regarding neurocognitive disability.8 I believe there is an implicit bias in medicine with regards to neurocognitive disability, especially within obstetrics. This bias, stated frankly, is that there is limited quality of life in the setting of neurocognitive disability, especially when severe (as is the case in both Trisomy 13 and Trisomy 18). The commonly used and pejorative language that I described above is evidence of this bias. Like other implicit biases, we need to be aware of the bias, learn how the bias influences the care we provide (or not provide), and work diligently to overcome it. The first step is modifying our language to meet evidence-based standards. I prefer to use the term diagnosis rather than syndrome or disorder when discussing genetic conditions and recommend this as a first step when teaching medical students and residents.

4. We need to respect parents of babies with trisomies and not react to their advocacy. For many parents of children with significant medical and genetic diagnoses, they believe that it is their job as parents to strongly advocate for their children.9 Many parents are aware through social media that their child is at risk for substandard care based on the genetic diagnosis (again, the implicit neurocognitive bias in medicine). They have read accounts of poor treatment of children with similar diagnoses and are ready to question and challenge their child’s medical team. This can be upsetting for the members of the medical team and may feel undermined or attacked. My recommendation is to take a moment to understand this perspective of the parent or family member and then to discuss it gently and supportively with the family.

5. Never underestimate the capacity of a parent or family to love and cherish their child regardless of their child’s genetic diagnosis. This part has been the most rewarding aspect of my career. I have come to know many families very well through our perinatal palliative care program and it is incredible to see how much they cherish their child even when their child’s life is expected to be brief.

(See photos)

6. Trust in medicine is more important now than ever and especially when caring for babies with trisomies. If trust can be established, then there tends to be less conflict and more collaborative decision-making with regards to the treatment plan for babies with trisomies. A comprehensive, multidisciplinary perinatal palliative care program can serve as an effective platform for creating trust among the family and health care team for babies with complex genetic conditions such as trisomy 13, trisomy 18 and even some cases of trisomy 21. I am a firm believer that perinatal palliative care needs to become the standard of care for each hospital that offers both obstetrical and neonatal services and that provides care for babies with trisomies.

I encourage all health care providers to take time this month and read about trisomy 13, 18 and 21 from an evidence-based resource. I recommend starting with S. Haug and colleague’s piece published in JAMA Pediatrics in 2017.10 I also recommend reflecting on the implicit neurocognitive disability bias in medicine and what that may mean for your practice. Reading “Lethal language, lethal decisions” can aid with this reflection.11 Finally, if the moral test of government is how it treats the children and the handicapped (using Hubert Humprhey’s words), then the same is certainly true of health care.

Vivienne Nicolazzo, diagnosed with Trisomy 18 during pregnancy and cared for in AHN’s Olivia’s Angels Perinatal Palliative Care Program (photos used with permission by family)

Vivi would have turned 4 years old on March 23rd 2023

References:

1. Former vice president Hubert H. Humphrey at the dedication of the Hubert H. Humphrey Building, November 1, 1977, Congressional Record, November 4, 1977, vol 123, p. 37287

2. https://Trisomy.org

3. https://mn.gov/mnddc/honoring-choices/cnnReports/Moral_and_Ethical_Issues4-Baby-Doe-Kappel.pdf

4. This is based on my own personal communications with parents of babies with trisomies over my career

5. Ann Thorac Surgery 2017 Jun;103(6):1941-1949. doi: 10.1016/j.athoracsur.2017.02.068. Epub 2017 Apr 26

6. TK Koogler, BR Wilfond, LF Ross. Lethal language, lethal decisions. Hastings Cent Report 2003 Mar-Apr;33(2):37-41.

7. This is based on my own personal communications with parents of babies with trisomies over my career

8. JD Lantos Ethical Problems in Decision Making in the Neonatal ICU N Engl J Med 2018;379:1851-60.

9. S. Huag et al. Using Patient-Centered Care After a Prenatal Diagnosis of Trisomy 18 or Trisomy 13: A Review.

JAMA Pediatrics, 2017; 171(4): 382-387.

10. Dr. Brian Carter, Lecture from PLIDA 2022 Meeting, October 12th, 2022; “Ethics and Perinatal Palliative Care”

ALLEGHENY COUNTY MEDICAL SOCIETY — 2023 MEETING SCHEDULE

ALL MEETINGS BEGIN AT 6:00 PM

Upcoming Events

No upcoming events Executive Committee*

Tuesday Evenings—2nd Tuesday at the start of each new quarter.

April 11, 2023

July 11, 2023

October 10, 2023

Committees

Delegation

Nominating

ACMS Honors

ACMS Foundation

Finance Committee

Tuesday Evenings

April 25, 2023

August 29, 2023

November 14, 2023

Board of Directors*

Tuesday Evenings

May 9, 2023

September 12, 2023

December 5, 2023

Dates to be announced

April, June, August, October

May, August

April 27, 2023 Heinz History Center

March 14 Planning Meeting/Special Grants

June 20 Prep for Grant Proposals

October 24 Grant Proposal Review

PAMED BOARD

May 4

August 3

AMA Interim Meeting

AMA Annual Meeting

PAMED HOUSE OF DELEGATES / HERSHEY

October 27-28, 2023

October 26-27, 2024

AMA HOUSE OF DELEGATES

June 10-14 Chicago, IL

November 11-14 National Harbor, MD

June 2024 Chicago, IL

January

February

May 29—Memorial

June 19—Juneteenth

July 4—Independence Day