StethoSCOOP Spring 2016

The

StethoSCOOP Cornell University Pre-Medical Society | Spring 2016

Global Health Medical Ethics Advances in Medicine Health in America Research

Gl obal Heal t h

Ebola and the Zika Virus: Thriving Diseases in a Medically Advanced World

By Alex Gordon

By Akila Venkataramany

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Medical Et hics

4 Women in Surgery & the Male-Dominated Culture of the Operating Room

Is Sharing Really Caring?

By Gabriella Alexandrou

By Henry Kanengiser

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Advances in Medicine

The Consequences of Internationally Banning Ketamine to Prevent Its Abuse

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Understanding the Complex World of Organ Transplantation

The Role of Pharmaceutical Companies in Online Health Communities

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By Lekha Patel

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Uterine Transplants:

Race for the Cure:

Transcatheter Aortic Valve Replacement:

A New, Controversial Form of Organ Donation

When Medical Technology Fails to Solve the Problem

A Novel Development for Less Invasive Surgical Procedures

By June Xia

By Aliya Ali

By Kevin Hui

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EBOLA AND ZIKA VIRUS Thriving Diseases in a Medically Advanced World

by AKILA VENKATARAMANY

In the past three years, severe disease outbreaks have dynamically changed the landscape of medicine in a time of modern technology. Within a few months of initial reports, both the Ebola virus and Zika virus have gained attention for the speed with which they were spreading. War and conflict pale in comparison to the damage a deadly disease can do, and as a result, people have become more aware of what actions to take in order to prevent these calamities in the future.

West Africa has been no stranger to the Ebola virus before, and the most recent outbreak suspiciously began in the town of Meliandou, Guinea, a former forested area razed by foreign mining and timber companies and home to 31 households. On December 26, 2013, an 18-monthold boy died after experiencing a fever, black stools and vomiting for two days. After officials

mistakenly identified it as cholera in early January 2014, the Institut Pasteur, a World Health Organization (WHO) Collaborating Centre, confirmed in March that the illness was indeed the Zaire species of Ebola, the most lethal virus in that family. Though the virus initially began in Guinea, it quickly spread to Liberia and then Sierra Leone to become the most deadly Ebola outbreak in history. As of January 2016, 28,637 Ebola cases and 11,315 deaths have been reported in the world, and most of them have been in Guinea, Liberia, and Sierra Leone. The WHO had initially declared the three countries Ebola-free, but some sporadic cases are still appearing in Guinea, forcing officials to remain vigilant.

Ebola can commonly be spread through contact with wild animals, and bats were the mode of transmission for the recent outbreak.

The StethoSCOOP | Spring 2016

People of West African cultures in Guinea, Liberia, and Sierra Leone rely on hunting wild animals for food, and bats are often hunted and eaten in Guinea. Once contracted, the virus is spread through unclean needles and direct contact with an infected person’s bodily fluids, including blood, saliva, sweat, vomit, semen, urine, and feces.

The Center for Disease Prevention and Control (CDC) believes Ebola is not airborne, although the airline industry has taken severe precautions anyways following a case appearing in Texas.

Several economic and medical factors contributed to the slow response to the Ebola outbreak.

The disease travelled to areas that are still among the poorest in the world and are more receptive to traditional healing than modern Western medicine. Since these countries were torn apart by war and conflict for years, basic healthcare infrastruc-

ture was severely lacking, and once the disease reached the capital cities, overpopulated conditions perpetuated its transmission. Hospitals were not trained in infectious disease protocol, leading the treatment centers to become prime areas to contract the disease. Healthcare workers were already extremely scarce prior to the outbreak, but the number available to treat individuals steadily declined as they too became infected. And socially, Ebola-ridden households were ostracized from the community, prompting people to hide infected family members and create unsafe living conditions. Most importantly, the WHO failed to convene a meeting to discuss the Ebola outbreak and declare a Public Health Emergency of International Concern until August 2014, by which point the disease was spiraling out of control. The lack of basic protocols and international action, combined with misunderstandings in the African 5

culture, most likely led to the high transmission of Ebola, and it is concerning that Ebola spread due to poorly managed problems.

Although the world seems to be recovering from the effects of the Ebola virus, a new illness is gaining attention. The Zika virus disease, a flavivirus spread by the infected Aedes mosquitos, is now primarily circulating in Oceania, Central America, South America, and the Caribbean.

The U.S. Virgin Islands, Puerto Rico, and some East Asian countries have also reported cases of the Zika virus disease. Discovered in 1947, the Zika virus has been detected in humans living in tropical climates for almost 70 years. Initial reports of the Zika virus infection in Brazil came from the Pan American Health Organization in May 2015, but the WHO declared Zika virus to be a Public Health Emergency of International Concern only in February 2016. Mosquito-borne diseases are quick to spread since the mosquito can reach several people in a short amount of time.

With globalization on the rise and the tropical climate, it makes sense that Zika took little time in affecting almost all of Central America and upper South America.

Though the mode of transmission for Zika is a mosquito, infected pregnant women can spread it to their fetuses; men with the virus can also spread it via their semen. Unlike Ebola, Zika presents only mild symptoms, including fever, joint pain, rash, and conjunctivitis; people often do not become ill enough to go to the hospital, leaving many cases to actually go undetected.

The disease is also closely related to chikungunya and dengue, both transmitted via mosquitos, and its common symptoms cause diagnoses to be difficult. Death by Zika is rare, and once a person has been infected by the mosquito, they are most likely protected from the illness in the future.

The alarm in recent months regarding the Zika virus comes from the drastic birth defects it seems to cause in babies born to infected pregnant women. Researchers have found the virus in the placenta and amniotic fluid of pregnant women who had babies with the sometimes deadly

microcephaly, which presents as abnormally small heads and underdeveloped brains. The brain tissue of a fetus with the illness also contained the virus DNA. In Brazil alone, the historical rate of microcephaly births was 0.5 cases per 10,000 live births, but this skyrocketed to 20 cases per 10,000 live births (for a total of over 3,000 cases) in the last six months of 2015. In addition, Guillain-BarrĂŠ, an immune system and neurological disease that causes worsening paralysis, has been potentially associated with Zika virus. Zika has not yet been officially linked to these birth defects due to the fact that blood tests for the virus are reliable for a period of one week after infection. Labs in Puerto Rico are currently working to find experimental ways to eliminate the Aedes mosquito in a short amount of time, and they are monitoring pregnant women in real time to learn more about the birth defects Zika could cause.

People often wonder why such powerful diseases have been able to cause as much trouble as they did. Though Ebola seems to have been magnified by human error, the Zika virus is aided by its mosquito vector. In order to prevent a catastrophe such as Ebola and Zika in the future, individuals need to be aware of any unusual symptoms that may arise, and they need to be proactive in bringing these problems to the attention of medical professionals, who must act swiftly in accordance with the gravity of the situation. Only then will the advancements currently available today be of use in controlling and containing potentially disastrous diseases.

IMAGE CREDIT: The Ebola Virus Poster, Visual Science, www.visual-science.com

Wh en M edi ci ne and M oney Col l i de:

NFL v s. CTE

By Uche Ezeh

The gam e of Am er ican football has changed the United States. The National Football League (NFL) has gr ow n into an $11 billion industr y, accr uing over 20+ m illion people in view er ship per w eek, pr esum ably sur passing that of any other non-NFL pr ogr am m ing [1]. The NFL has becom e so popular am ong Am er ican view er s and spectator s that it even has its ow n day of the w eek, com m only r efer r ed to as Sunday NFL Football.

W hile being an industr y that pr esents a for m of enter tainm ent, it is still a business. League officials including Com m issioner Roger Goodell go to consider able lengths to m aintain a good im age or as Goodell w ould r epeatedly say, ?to pr otect the shield?. Accor ding to Gr antland, this saying ?[w as] his w ay of dr am atizing his solem n, possibly chivalr ous duty to the league, its im age, and its billions of dollar s of annual r evenue [2].?

The StethoSCOOP | Spring 2016

Over the last couple of decades, the NFL had been scrutinized by its former players for not discussing with them the damaging effects the game of football could have long after their career, specifically to their brains. According to CNN, former players had suggested in a 86 page lawsuit filed in Los Angeles, that the NFL's Brain Injury Committee was cognizant about the long-term brain injury risks associated with the hits they engaged in during games [3]. It can be safely assumed that the League refused to be transparent about these findings with their players because it would have possibly deterred athletes from the game. Due to the NFL?s lack of transparency, the league was sued by thousands of former players who were suffering from neurocognitive illnesses, and the final settlement awarded them 900 million dollars to help with treatment of their neurological conditions [4]. Currently, the NFL has drastically changed its evaluation protocol of players who sustained hits to the head during games. However, while the NFL may have been able to surpass the recent storm regarding concussions, an even bigger storm has arrived - a disease that can?t be diagnosed while living and may also be the cause of early age deaths in American football players.

Chronic Traumatic Encephalopathy (CTE) is an aggressive neurodegenerative disease incurred by repetitive brain trauma. It is commonly associated with clinical symptoms such as memory loss, aggression, depression, suicide, lack of impulse control, and even progressive dementia [5]. At the moment, CTE can only be confirmed post-mortem. Nevertheless, according to Dr. Bennet Omalu, a neuropathologist who first discovered CTE, there are several consistent clinical manifestations for CTE including ?deterioration of the hippocampus and other medial temporal structures?[6] and even accumulation of hyperphosphorylated tau protein? abundant in neural cells and promotes tubulin assembly in microtubules? as tangles or aggregates in areas such as the front and temporal cortices, brainstem and spinal cord [7]. This same protein has been found to contribute to the pathology of other neurodegenerative diseases such as Alzheimer?s and Parkinson?s disease.

Dr. Omalu first discovered CTE in a mortem analysis on former Pittsburgh Steelers center Mike Webster. Before Webster suddenly died, many close to him characterized him as being different; he was suicidal, depressed, addicted to drugs, suffering from dementia, and homeless. It was during an autopsy that Dr. Omalu had noticed a unique pattern of tau accumulation in Webster?s brain, which led him to think that the repeated blows that Webster had endured during his 16 year NFL career were what led to his severe brain injury. Other famous players such as former Chicago Bears safety Dave Duerson and

former Chargers linebacker Junior Seau committed suicides in their mid 40?s and early 50?s respectively, and both their brains were positive for CTE. Dr. Ann McKee, a neuropathologist and also co-director of the Boston University School of Medicine Center for the Study of Traumatic Encephalopathy, also weighed in on this phenomena with CNN, explaining how ?[seeing] the kind of changes we're seeing in 45-year-olds is basically unheard of.?[8] A study by the NFL Player Care Foundation found that 6.1 percent of NFL retirees over 50+ in age were diagnosed with some type of dementia in comparison to 1.2 percent of all US men within that age group [9]. In addition to these statistics, the VA-BU-SLI Brain Bank confirmed that 59 of 62 deceased former NFL players? brain tissue tested positive for CTE [10]. But, while this percentage of pathologically confirmed CTE is remarkably high, it must be noted that there might be selection-bias given the fact that many of the brains donated were from high profile football players.

Nevertheless, the pathologically confirmed cases of CTE in football players should be taken seriously given the CTE medical literature to date. Yet despite this, the NFL still didn?t take the claims made

by Dr. Omalu seriously for reasons that cannot be understood. The film, Concussion, starring Will Smith as Dr. Omalu, showed the efforts taken by Dr. Omalu to warn the NFL about the danger of CTE and the unwillingness of the NFL to let him feed into the fear over football?s physical toll. It wasn?t until as late as March 15, 2016, that a NFL?s health and safety officer finally acknowledged in front of Congress that there was a direct link between neurodegenerative diseases such as CTE and football-related trauma. And this is a link the NFL didn?t have to confirm in the previous aforementioned lawsuit [11]. However, even this long-awaited revelation was met by criticism by NFL personnel including Dallas Cowboys? owner Jerry Jones, who is not convinced of a link between CTE and football, stating that there is ?no way in the world to say you have a relationship relative to anything here? there?s no research. There?s no data? .?[12].

Head coach of the Arizona Cardinals Bruce Arians stated in response to the NFL health and safety officer that: ?there are more concussions in girls soccer than in football at that age. But no one says we gotta stop playing soccer? It?s the same thing with knee injuries. There are more knee injuries at eight to 12 in soccer than in football. You can find all the statistics you want if you want to crucify something? [13].

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While this rhetoric by both individuals can be viewed as harmful and ignorant, it?s important to note that their statements do address some of the missing links that still need to be established: not all football players that are deceased suffered from CTE; and the NFL has increased its safety protocol, especially in regards to concussions, in the last decade to address

growing concern over brain injury risk. Nonetheless, both critics and supporters of the findings on CTE can agree that the safety of the players will always be of concern. In the future, the NFL and neuropathologists should be moving forward with more research that informs athletes, from the amateur-level up, of the risk they are taking playing a sport such as football.

The StethoSCOOP | Spring 2016

I s Sh ari ng Real l y Cari ng?

The Rol e of Pharmaceut ical Companies in Onl ine Heal t h Communit ies

By Henry Kanengiser

The Inter net has pr ofoundly changed ever y aspect of our lives, and our health is no exception. M or e than 50% of all Am er ican adults use the Inter net for m edical infor m ation: to find a doctor for their condition, to contact exper ts acr oss the globe, and to com m unicate w ith other s w ith the sam e ailm ent. Online illness suppor t com m unities (OISCs), such as Daily Str ength and the Kids W ith Food Aller gies, ar e developing as places w her e people w ith sim ilar and often r ar e illnesses pr ovide com for t to one another and ask questions about their shar ed exper iences.

W hile OISCs m ay be lauded as another benefit of living in the Infor m ation Age, ther e is a specter often over looked or hidden fr om the

com m unity?s user s: the r ole and pr esence of phar m aceutical com panies. M any of these OISCs ar e affiliated w ith phar m aceutical com panies in w ays that ar e not fully m ade aw ar e to the public.

In the Web 2.0 er a favor ing individual contr ibution, OISCs ar e a highly valuable com m odity for phar m aceutical com panies. They can function as a fr ee sour ce of detailed m edical infor m ation for these phar m aceutical com panies, often w ithout the full consent of com m unity m em ber s.

The som ew hat nefar ious r ole that phar m aceutical com panies play in these com m unities cr eates an ethical dilem m a. Illness com m unities m ay w ant to be connected to a phar m aceutical com pany that m akes m edicine 11

for them , since they w ill have a better oppor tunity to have their opinions hear d.

How ever , in a content-heavy w eb envir onm ent w ith em phasis on shar ing exper iences, how m uch of this per sonal infor m ation intended to be shar ed w ith a com m unity of sim ilar ly ill individuals should be accessible to a phar m aceutical com pany pr ofiting off the com m unity? The lack of full consent given by people in these online health com m unities to phar m aceutical com panies to use their per sonal infor m ation dem onstr ates an ethical flaw in the setup of these online illness com m unities. To solve this pr oblem , online health com m unities should be kept separ ate fr om phar m aceutical com panies altogether.

We live in an Inter net age called Web 2.0, w her e the Inter net exists as, ?a continually-updated ser vice that gets better the m or e people use it, consum ing and r em ixing data fr om m ultiple sour ces, including individual user s.?

Essentially, OISCs cr op up as w ays for individuals to find other s w ho have shar ed sim ilar exper iences w ith their illness, and find solidar ity. In this er a, how ever , as analyzed by Debor ah Lupton, ?it is suggested that individuals becom e good citizens by par ticipating in these technologies and contr ibuting their exper iences so that they m ay be aggr egated for the gr eater good.? Rather than r eading an online copy of m edical texts, an individual w ith a r ar e disease can com m unicate w ith people living thr ough the sam e str uggles as them .

OISCs ar e an inter esting r esult of this shift in the w ay the Inter net is used. Som e for um s str ongly encour age r eader s to ?digitize them selves?, Lupton calls it, ?r ender [ing] their bodies into digital for m using the m onitor ing technologies to pr oduce data that m ay be quantified and tr ansm itted to other s for their per usal?. This cr eates an envir onm ent w her e people can not only help one another keep tr ack of their illness and their pr ogr ess in conquer ing it, but can also or ganize as an activist body, dem anding change in m edicine w ith the physical of body of evidence necessar y to pr ove the point.

Besides being a m or e em pow er ing platfor m for r eaching out to the phar m aceutical com pany, individuals ar e often dr aw n to these com m unities because of the suppor t they pr ovide. W hether for people w ith chr onic pain, ALS, one of m any m ental illnesses, or one of m any other illnesses, the im por tance of these com m unities is evidenced by their popular ity.

OISCs exist for alm ost ever y long-ter m and chr onic illness im aginable. Online health com m unities have been linked to gr eater quality of life, better decision m aking, and patients feeling less alone and m or e em pow er ed.

Phar m aceutical im pact on OISCs cam e to the for efr ont of m edical ethics conver sations over the quiet connections betw een WebM D suppor t com m unities and sever al phar m aceutical com panies. A 2013 study in JAM A found that WebM D r eceived m or e than $20 m illion in com pany gr ants, r aising the ethical question of if they ar e attem pting to pr ovide factual infor m ation or just sell dr ugs. The w ebsite, one of m any w ith its com m unities m onitor ed and infor m ation alter ed by lar ge phar m aceutical com panies, ?has becom e per m eated w ith pseudom edicine and subtle m isinfor m ation?.

Even m or e alar m ing ar e the m ethods em ployed by phar m aceutical com panies to appear distant fr om these com m unities. A study of 69 patient or ganizations of var ying sizes r evealed that only one thir d of patient or ganizations w er e clear in their funding connections, and the r esear cher s concluded that online com m unities in gener al, ?do not pr ovide enough infor m ation for visitor s to assess w hether a conflict of inter est w ith Phar m a exists.? Although disclaim er s exist, investigations into and outr age about violations of pr esum ed pr ivacy continue to occur.

Is close connection to phar m aceutical com panies a net good for these com m unities?

W hen illnesses ar e r ar e and com m unities ar e sm all, som e ar gue, having the attention of a phar m aceutical com pany is har d to do.

Pr oviding phar m aceutical com pany w ith easily accessible health data m ay m ake this com m unity?s tr eatm ent easier. How ever , this

"Is close connection to pharmaceutical companies a net good for these communities?"

The StethoSCOOP | Spring 2016

br ings up the question of full consent. Ethically speaking, a patient m ust not feel coer ced or m isled in any w ay w hen deciding to shar e their infor m ation online.

In cases w her e phar m aceutical com panies cover tly m ine OISCs for per sonal infor m ation, the ar gum ent in favor of phar m aceutical involvem ent often encour ages unethical activity.

Spur r ed on by inter nal com m unity pr otests over the shar ing of per sonal data as w ell as lar ger investigative r esear ch into the r ole of phar m aceutical com panies, online health com m unities have tr ansitioned to m or e tr anspar ent adm inistr ative str uctur es.

Com panies such as Patientslikeme have pages

listing their par tner s, encour age openness, and their pr ivacy policy delineates clear lim its to data that they m easur e. All of this is now out in the open, available for any per son to r eview befor e signing up for the com m unity.

W hile som e com m unities continue to hide their connections in layer s of online bur eaucr acy, patients ar e now pr ovided m or e online options that ar e actively separ ate fr om phar m aceutical com panies. W hile individuals in these com m unities encour age the shar ing of infor m ation, they do it w ith an eye to the instances in w hich pr ivacy is pr otected as w ell as those w her e it is not. jjjjjjjjjjjjjjjj jjj

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The Consequences of Internationally Banning Ketamine to Prevent Its Abuse

by ALEX GORDON

The StethoSCOOP | Spring 2016

Under most circumstances, banning a harmful recreational drug would be universally beneficial, but what happens when such a drug has a valid medical purpose in low-income countries? This is the question that the United Nations Commission on Narcotic Drugs will attempt to answer at its 59th session in Vienna, Austria.

Ketamine, the drug in question, was initially used as a horse tranquilizer, but it also can function as an anesthetic in humans. As an antagonist of the NMDA receptors present in many nerve cells, ketamine prevents the transmission of nociceptive signals to the brain, leading to sedation. In lowincome countries like Kenya, ketamine is frequently used in this capacity because it can be administered as a pill, without the supervision of an anesthesiologist.

If the CND places an international ban on ketamine, these countries will lose an invaluable medical resource.

In medically advanced countries like the United States, many people fail to recognize the impact that ketamine has on healthcare in impoverished countries. A study recently published by the World Health Organization found that in the 22 low and middle-income countries (LMICs) surveyed, 40% of hospitals did not have anesthesia machines, and 35% did not have oxygen machines (Vo et al., 2012). As ketamine can be used as an anesthetic without these

machines, it is invaluable in these hospitals. A program known as “Every Second Matters-Ketamine” found that after only five days of training, non-anesthetist clinicians were able to use ketamine as an anesthetic with no major adverse results in 193 consecutive surgeries (Burke et al., 2015).

Additionally, a recent article published in The Lancet highlighted many uses of ketamine to argue against the international ban, claiming that “recreational use of ketamine should not prevent millions of people from surgery under the only anaesthetic in LMICs, or its use in disaster and conflict trauma, and in veterinary medicine” (Taylor et al., 2016).

While ketamine is very useful in medical contexts, it can cause many adverse health effects when abused. It is an example of a dissociative anesthetic, meaning that its users claim to feel an outof-body experience. Other psychological effects of ketamine include hallucinations and detachment from reality. Ketamine use can have several short-term side effects like disorientation, nausea, and vomiting. Additionally, many ketamine users injure themselves without realizing because the drug acts as an anesthetic. Long-term ketamine abuse can lead to serious dependence as well as bladder and kidney problems. In some cases, ketamine use thickens the walls of the bladder so much that urine 15

cannot pass, ultimately requiring the bladder to be removed.

The abuse of ketamine, despite posing such massive health risks, is prevalent in Asia, Europe, and the United States. According to the BBC, ketamine is the fourth most commonly used recreational drug in the United Kingdom. It is understandable that these countries would want to ban ketamine due to its harmful effects, but it is somewhat surprising that the main country pushing for the international ban is China, which produces the majority of the world’s ketamine.

Martin Jelsma of the Drug and Democracy Programme at the Transnational Institute in Amsterdam claims that China’s proposal is an attempt to appease other Asian countries. This points to the obvious question: why can’t China regulate its own production and exportation of ketamine? Attempting to do so could reduce ketamine abuse worldwide while allowing countries like Kenya to continue using ketamine for medical purposes. Professor Zhimin Liu of the National Institute on Drug Dependence at Peking University claims, “It is far from sufficient to rely on regional or national measures alone in combating a newly emerging substance such as

ketamine which poses a health hazard.” Even if this is true, banning ketamine to prevent its abuse is ethically questionable because of the necessity for the drug in underdeveloped countries.

Some officials are concerned with the motives of those pushing for the international ban of ketamine. Emmanuel Makasa, Zambia’s representative at the World Health Organization in Geneva, states, “Most of the representatives sitting at the Commission on Narcotic Drugs control are coming from law enforcement [and] they are not coming from public health.”

Accordingly, these representatives may believe that the health risks of ketamine outweigh its benefits in other countries. The decision reached by the Commission of Narcotic Drugs will likely depend on how its members evaluate the usefulness of ketamine in low and middle-income countries. Unfortunately, many of these nations do not have permanent diplomats in Vienna, so their interests will not be fairly represented at the meeting of the CND. This dilemma is best captured by the words of Mike Trace, a former official at the UN Office of Drugs and crime: “some of the developing countries who would be most affected by this decision, are not here.”

The StethoSCOOP | Spring 2016

RACE FOR THE CURE

When medical technology fails to solve the problem

by ALIYA ALI

In the past decade, the medical field has made a big jump in innovative technology that helps cure certain diseases that were long thought to be incurable. These diseases range from cancer, to HIV, to Alzheimer’s. A lot of different methods have been developed over the years to find curative solutions for them, and many of these methods have benefitted from modern technological advances.

Despite these important footsteps, access to these technologies remains limited in most parts of the world. To counteract this large development gap, efforts have been put in to increase accessibility of this machinery by multiple ways. We may ask ourselves if these are enough.

Throughout history, research has permitted medicine to advance quickly. For example, stem cell technology has helped a lot in curing rare diseases and cancers. Recently, it also permitted us to recreate entire organs from just using a scaffold and stem cells. Professor Robert Langer at MIT is a pioneer in that medical technology field. Another field that is greatly advancing is cancer treatment using new RNA technologies and biomedical engineering techniques. However, these technological advances are not without their drawbacks. Problems arise with the accessibility of those technologies that require enormous amount of funding.

Even though these innovations are able to change the face of medicine, they remain inaccessible to

most patients. Not only does this result in a gap between hospitals near active research hubs and those that are more isolated, but this also creates a huge separation between developed countries and developing countries.

Some initiatives have been put in place to bridge the gap with the use of the Internet, such as live webinars between technology hubs and hospitals in developing countries. The way those work is that doctors working in developing countries’ hospitals communicate live with doctors or researchers from leading research universities to talk about new cure methods. Likewise, a lot of resources are put on the Internet to get information and data about diseases; however, this doesn’t solve the problem of accessibility to technology, but merely the one of communication.

In the past five years, a lot of easily accessible technological advances have appeared in health tech startups. Since the popularization of smartphones in many parts of the world, several startup companies have created applications on smartphones that allow patient health tracking or connect to a patient’s electronic medical record (EMR) at the hospital in which they are being treated. This not only allows patients to be more aware of their health conditions, but also results in patients being more compliant with doctors’ requirements.

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Tablet interface for an open-source health app. IMAGE CREDIT: Juhan Sonin / Flickr. CC BY 2.0

One company that developed this aspect of selftracking is AiCure, an application that uses artificial intelligence to track whether patients have taken and swallowed their medication on time, and at the appropriate dose. The app works with the camera of your phone, which detects whether you have taken your medicine or not. Rather than merely using a video, AiCure uses the forefront of artificial intelligence to allow a doctor to detect if you are taking the right medication and to see whether you have actually taken it or cheated.

Johnson & Johnson is also a fervent pioneer in this field. By partnering with Apple and IBM, the company has put in place several coaching apps such as Care4today, HealthyDay, CaringCrowd, and Gutcheck. HealthyDay is an app that allows

you to get healthy tips throughout your day based on your medical condition. Care4Today is a health tracker for doctors and family members of a patient to use to track a patient’s health progress and updates.

These apps have assuaged a lot of problems with patient follow-up care, and decreased patient readmission rates significantly over the past few years. However, they don’t solve the problem of making newest technologies accessible worldwide. Even if the general thought is that smartphone usage is common in countries like the United States or countries in Europe, 80% of the world population doesn’t have access to that tool; therefore, these apps are not accessible to the majority of the population.

The StethoSCOOP | Spring 2016

Several startup companies have created applications on smartphones that allow patient health tracking or connect to a patient’s electronic medical record (EMR).

Other means are thus provided by some innovators in the world of medicine to bypass computers and still make innovative medical works to the most people. Theranos is a great example of that.

In 2003, Elizabeth Holmes, a 19 year-old Stanford drop out, found an alternative to make the newest blood testing technology accessible worldwide by creating Theranos. Theranos’ revolutionary blood testing technology has overthrown traditional lab testing by providing cheap and fast blood testing that requires only one drop of blood from the patient. The way the Edison blood testing device works is with a simple stick that withdraws a tiny blood sample that then gets run into a reader, and in a few hours, the test results are available. The test gets ordered at a local provider where you can obtain your stick and then your results. Until recently, that local provider in the United States was Walgreens.

Theranos had projects to expand its cheap testing device to villages in India and African countries. That could have been an avant-garde way to implement low-cost blood testing for a lot of people living not only in cities but also in secluded rural areas. That technology could was targeting a much wider range of patients than only those using smartphones.

Last year however, Theranos got involved in many controversies. The test allowed by the Edison device is not FDA approved. The reason for that restriction is that according to the FDA, the test results are not accurate, especially when it

comes to more complex blood testing such as STD detection. The major criticism that has been made towards Theranos is that, 1. there is no nurse involved in the process of blood sampling, so agencies claim the device could be harmful to people; and 2. the blood tests are not accurate enough since they require such a low amount of blood. In contrast, others argue those two main arguments as questionable, citing how diabetic patients have been handling needles for a long time now.

Healthcare technology is improving at an increasing rate every day leading to many medical problems being eradicated at the frontier. However, the healthcare industry overall is lagging behind, and the gap between what we know we can cure and what is actually being solved is widening. Medical centers in developing countries are now far behind medical research centers and they are struggling to keep up. While communication technology has tried to bridge this gap, there is still much room for improvement. The medical industry is not stagnating, but rather the frontier is leaving behind the goal of curing patients at a large scale. Other companies have tackled with this problem, but their solutions bring with them a series of ethical quagmires. How far can we go? Is there a point where technology starts degrading healthcare more than it’s helping it? For now, there is potential for making technology more accessible worldwide, and the medical field is growing in the right direction to achieve that objective.

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The StethoSCOOP | Spring 2016

Understandi ng th e Compl ex Worl d of

Organ Transpl antati on

By Lekha Pat el

The advent of or gan tr ansplantation changed and continues to change how m edicine is pr acticed in the m oder n day. Or gan tr ansplantation, fir st, becam e popular as a m ethod to tr eat ter m inal diseases at the beginning of the 20th centur y, such as liver failur e or bodily infections. How ever the lack of im m unosuppr essants pr evented r ecipients fr om fully r ecover ing after sur ger ies until the ear ly 1970s. The ver y fir st successful or gan tr ansplantation, in w hich the r ecipient lived, w as per for m ed less than 40 year s ago and w as the fir st successful hear t-lung tr ansplantation. Since then, or gan tr ansplantation has becom e m or e

successful.

Now , the m ost com m only tr ansplanted or gans ar e the hear t, liver , and kidneys. As can be expected, the r ise in dem and for or gan tr ansplants has r esulted in an exponential incr ease in or gan needs.

In the U.S. the UNOS? United Netw or k for Or gan Shar ing? r egulates or gan tr ansplantation.

How ever , the inter m inable scar city of tr ansplant or gans ar ound the w or ld has given r ise to or gan tr afficking netw or ks in w hich people ar e abused into donating or gans and selling them for little pr ofit. The illegal and black tr ade m ar kets have necessitated the cr eation of a new inter national code of ethics for hum an tr ansplant sur ger ies.

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The buying and selling of or gans is seen less as a w ay to give life to people w ho need vital or gans, and m or e as an exchange of com m odities: m oney for or gans. This can be seen not only in thir d-w or ld countr ies but also in places such as New Yor k City and San Fr ancisco, w hich ar e both heavily populated and ur banized.

Or gan tr afficking in fir st-w or ld nations speaks of another m ajor issue in or gan tr ansplantation: doctor s seeking to gain pr ofit in the or gan tr ading business, or use illegal m ethods to help their patients. Accor ding to Scheper -Hughes, or gan tr ading has been linked physicians and biom edical pr actitioner s to pr isoner s and gang leader s that ar e in the low est str ata of the cr im inal w or ld. A few year s ago in New Yor k City, tw o tr ansplant sur geons w er e caught tr ying to negotiate the pur chase of cor neas, kidneys, and liver s fr om Chinese seller s in the ar ea. The m ost hair -r aising stor ies of or gan tr ansplantation unsur pr isingly occur in thir d-w or ld countr ies. In South Afr ican countr ies, India, and China, ar eas w her e ther e ar e lar ge classes of im pover ished people, people ar e often ?taken to get tr eated by doctor s? but w ake up w ith or gans m issing instead. The r ise in global or gan tr afficking and its link to physicians has gr eatly incr eased feder al sur veillance of suspicious or gan tr ading activities all over the w or ld, including the U.S. The m ost com m on locations for black m ar ket or gan tr ading ar e India, China, and m any Afr ican countr ies, ar eas w her e ther e ar e few political bar r ier s to fight black m ar ket or gan tr ading. India is the pr im ar y site for dom estic and inter national tr ade in kidneys, and most of these or gans ar e taken fr om poor , uneducated, and easy m anipulable people w ho ar e tr icked into ?going to the doctor ? or kidnapped. These ?donor s? (for lack of a better ter m ) w ill likely not have access to or r eceive any dialysis tr eatm ent, w ithout w hich they cannot live a long or healthy life. The buyer s and seller s in this scenar io tr eat

kidney as a com m odity they can ?buy?and ?sell?in differ ent par ts of the w or ld. The long-ter m em otional and physical effects on the donor s, their fam ilies, and the com m unity is deem ed m inute in com par ison.

In South Afr ica, state funds ar e used for pr im ar y car e, w hile dialysis and tr ansplant sur ger y have m oved to the pr ivate sector , w her e only the elite can get the or gans they need.

Recipients m or e likely die fr om infections and hepatitis r ather than the lack of im m unosuppr essants because donor s ar e often poor and possibly sick .

The r ole of doctor s in or gan tr ansplantation can be just as concer ning as the activities of global tr ading netw or ks. W hen ther e is a lack of or gans in the hospital for a patient, tr ansplant sur geons have been found to pr essur ize fam ily m em ber s of r ecently deceased patients to donate healthy or gans. In these situations, doctor s can, unknow ingly, star t to think of or gans as a com m odity, as w ell. They have a patient that desper ately needs a tr ansplant and a potential donor. The r eal question in this hospitalized and ?legal?or gan donation m ethod is w hether doctor s can inadver tently ?for ce? patients and their fam ilies into donating or gans and w hether this constitutes ethical or gan tr ansplantation pr actice. It is a doctor ?s r esponsibility to tr eat his/her patients, but is it ethical to pr y for or gans fr om r elatives of a r ecently deceased patient.

The political and bioethical dilem m as sur r ounding or gan tr ansplantation ar e being published and m or e actions ar e being taken than ever befor e. It is a ver y com plex issue that spans not only acr oss global netw or ks but also w ithin hospitals and betw een doctor s. Ther e is a clear distinction betw een global or gan tr afficker s w ho steal or gans fr om the under pr ivileged, and doctor s w ho w ant an or gan because they w ant to save a patient, but the or gan tr ading has becom e a pr im ar ily ethical dilem m a w ith the r ise in illegal activities r elated to it.

Women i n Surgery

&

The Male-Dominated Culture of the Operating Room

By Gabriella Alexandrou

It is no secr et that ther e ar e pr ofessions w her e one gender dom inates. In 2012 m en com posed 99% of car pentr y positions, and 92% of vocational nur ses w er e w om en. Fem ale par ticipation in tr aditionally m asculine occupations, such as police officer s and dentists ar e continuing to incr ease, and m edical school enr ollm ent has r em ained at a steady 50:50

gender divide for the past couple decades.

Although gender ster eotypes w ithin the Am er ican w or kplace ar e slow ly br eaking dow n and w om en now constitute half of m edical school gr aduates, ther e still exists evident gender discr epancies w ithin specific m edical subspecialties. The specialties w ith a significant por tion of fem ale physicians ar e those that tend 23

to have a m or e ?m ater nal? natur e, such as child and adolescent psychiatr y, pediatr ics and neonatal-per inatal m edicine. It is w ithin the sur gical specialties that pr acticing fem ale physicians ar e com par atively non-existent. In 2010, w om en sur geons com posed 7% of vascular sur geons, 6.5% of neur ological sur geons, 4.6% of thor acic sur geons, and a m er e 4% of or thopedic sur geons. W hen looking at these num ber s, it is im por tant to under stand the social contexts that shape them . Sexism in the w or kplace, m asculinity r equir em ents w ithin the sur gical com m unity, and expectations for w om en to be a fam ily car egiver lim it oppor tunities for w om en in the sur gical field.

Because people tend to avoid unfr iendly w or kplace envir onm ents, the highly sexist exper ience of being a fem ale sur geon m ay encour age w om en to seek other specialties.

Accor ding to a sur vey conducted by Cliff Str aehley, M .D. and Patr izia Longo, Ph.D. for the Am er ican Jour nal of Sur ger y, over 75 per cent of w om en sur geons exper ienced gender discr im ination in their car eer s. Wom en in a hospital ar e often m istaken as secr etar ies, or , if in scr ubs, as nur ses. Dr. Niam ey W ilson, an Am er ican br east cancer sur geon, w as r efer r ed to as ?lady doctor ? and over looked even though she w as the Chief Resident. Instead, patients dir ected their gaze to her m ale subor dinates w ho, incidentally, w er e not r efer r ed to as ?m an doctor s,? but r ather , ?doctor s?.

Per ceptions of the appr opr iate qualities a sur geon should possess m ay also be biased against w om en. Am ong sur geons, a m asculine dem eanor is often expected over one that could be consider ed m or e ?fem inine.? Sur gical r esidents ar e pr aised for displaying a constant tough exter ior w hile toler ating long hour s and little sleep. Any em otion is adm ittance of incom petence and not fit for the br other ly cam ar ader ie that seem s to infiltr ate sur gical pr ogr am s. Accor ding to Dr. Laur en Cr aw for d, a plastic sur geon in Texas, w om en sur geons have m or e to pr ove. On a w om an?s fir st day she ?w ill quickly be sized up by [her ] m ale counter par ts.

Too em otional? Too bitchy? Too pr etty? Not pr etty enough? Weak? Likely to get pr egnant?

Annoying? Over talkative? And ultim ately, not a good fit for sur ger y?? And especially w ithin the m or e m ale-dom inated specialties such as or thopedics, a w om an is ?assum ed to be a liability until pr oven other w ise.?

Fur ther m or e, the tim eline of a sur gical

car eer is such that car eer gr ow th and pr im e fam ily gr ow ing year s ar e pit against each another. In the United States, the aver age age a w om an gets m ar r ied is 27, w hile the aver age age of fir st-tim e m other s is 26. If the ?aver age? w om an follow s these guidelines and chooses to have m or e than one child, she w ill be giving bir th w ell into her sur gical r esidency, w hen the hour s ar e longer and m or e str essful. In our patr iar chal society, m en ar e r ar ely pr essed to m ake tim e to car e for their fam ily thr ough their sur gical education, leaving fem ale sur geons w ith double the w or k . Dr. W ilson r em em ber s r etur ning to w or k after m ater nity leave and being for ced to pum p m ilk in the on-call r oom s in betw een seeing patients, and not seeing her childr en for sever al days because she w ould leave for w or k befor e they aw oke and r etur n after they had alr eady gone to bed. Ther e w as also the additional scor n and disappointm ent she w ould r eceive fr om her r elatives as she began spending m or e tim e on her car eer. She could not tur n to her fam ily w hen exper iencing these inter nal str uggles because she knew they alr eady judged her for her long hour s, and she could cannot tur n to her colleagues for fear of being per ceived as w eak .

Unfor tunately, her exper ience is not a r ar ity of fem ale sur geons: ?We begr udgingly accept this level of m isogyny and anti-fam ily sentim ent w hen it?s subtle, constitutive and m ixed w ith pr aise for being tough. After all, this is sur ger y. And sur geons ar e tough.?

Ther e is, how ever , hope that the m ale-dom inated sur gical cultur e is w eakening, as evidenced by social m edia cam paigns and shifts in view points w ithin the m edical com m unity. In 2015 the ?I look like an engineer ? hashtag cir culated thr oughout Tw itter and Instagr am , in w hich fem ale engineer s posted a pictur e of them selves w ith the statem ent ?#ILookLikeAnEngineer ? in the caption to challenge engineer ing ster eotypes. ?#ILookLikeASur geon? quickly follow ed suit. A 2012 study by Br ow n et al. w as the fir st to find that m ale sur geons endor sed m ater nity leave, w ith a fem ale par ticipant noting, ?The volum e of w om en has m ade [longer m ater nity leaves] m or e the nor m ? that w ould never have happened befor e? Those ar e ver y pr oductive sur geons w ho ar e r espected, so they?r e not dem eaned anym or e? (1). These changes ar e felt by m ale sur geons as w ell. One m ale par ticipant noted, ?We?r e seeing m or e and m or e m ale sur geons

The StethoSCOOP | Spring 2016

w ho ar e doing m or e stuff at hom e ? and they?r e also having to leave ear ly to pick up their kids because their w ife is w or king too? So it?s changing.

It?s not like how it used to be, 20 or 30 year s ago.? This gener ational change confr onts the str ongly r ooted expectations w ithin the sur gical cultur e that sur geons m ust live and die by their w or k . The study concluded that the fem ale sur geons they inter view ed w er e m or e satisfied w ith the tr eatm ent they r eceived fr om their m ale colleagues because the depar tm ent and the lar ger institution w er e in tr ansition, m eaning they allow ed m or e flexible hour s, pr eventing both the fem ale and m ale sur geons fr om having to decide betw een their fam ily and their car eer.

Leveling the gender distr ibution in the sur gical field and im plem enting m or e w ays to im pr ove the par ticipation of w om en is vital to our society. Wom en should not be told, w hether im plicitly or explicitly, that in or der to becom e a top sur geon, they need to develop a m asculine ener gy, conceal their fem ininity and abandon tim e w ith their fam ilies. Avenues need to be pr ovided for sur geons to have m or e flexible hour s and r educe the ?live in the hospital? m entality that per m eates the envir onm ent of m any oper ating r oom s. Although 30% of sur geons ar e fem ale, this per centage pales in com par ison to the 50% that annually gr aduate fr om Am er ican m edical schools. M or e needs to be done to actively r ecr uit fem ale m edical school students into specialties that show a dear th of fem ale involvem ent, like or thopedic and ur ologic sur ger y, w hich ar e alm ost entir ely m ale. Only this can tr uly r em edy the sever e paucity of fem ale m entor s. These next steps ar e vital to ensur ing that w om en ar e pr ovided w ith the oppor tunities to be confident, successful leader s in their sur gical fields.

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T cells (green) attacking a cancer cell.

GRAPHIC CREDIT: Adriana Lippy / Fred Hutch

Immunotherapy Treatments for Bloodstream Cancers is New “Baby Step”

by JONAH KLAPHOLZ

The StethoSCOOP | Spring 2016

Dr. Stanley Riddell is a member of Fred Hutch’s Clinical Research Division and a co-founder of the Program in Immunology. IMAGE CREDIT: Bo Jungmayer / Fred Hutch News Service

Cancers of the circulatory and lymphatic systems have a long and complex history. Leukemia, lymphoma, and myeloma account for 9.8 percent of the estimated 1.65 million cancers diagnosed in the United States each year, making them some of the more prevalent cancer cases. These cancers cause about 56,000 deaths in the U.S. every year and are also known for their many forms that vary in severity. Among the most severe include acute lymphoblastic leukemia and non-Hodgkin’s lymphoma, both of which begin when the immune system’s lymphoid cells in the bloodstream and lymphatic system begin to multiply out of control.

In late stages these cancers are difficult to treat. Traditionally, patients have resorted to chemotherapy and radiotherapy, treatments that have only saved about 50 percent of late-stage leukemia and lymphoma patients in the United States throughout the last two decades. The fiveyear survival rate is even lower. Research labs have been hard at work attempting to discover a more effective treatment. And in February 2016 they announced that they might have found one.

A new form of immunotherapy may serve as a breakthrough in treating cancers of the bloodstream and lymphatic system. It involves

the modification of a patient’s immune system to target and destroy a cancer. While the new method looks promising, as it has the potential to act more quickly and forcefully than traditional treatments, it has yet to be perfected, and has caused some controversy in the cancer research community.

Researchers at the Fred Hutch Cancer Research Center in Seattle first recognized the potential of the new immune system-based approach in a trial they began in 2013. Under the leadership of Professor Stanley Riddell, they gathered terminal patients suffering from advanced lymphoblastic leukemia and non-Hodgkin’s lymphoma and administered their experimental treatment.

Instead of trying to construct a new drug, Riddell and his colleagues decided to harness the human immune system, something that is widely studied and easily accessible.

Immunotherapy for cancer treatment is not a new idea. Oncologists have been suggesting that strengthening the body’s immune system by increasing the amount of T-cells in the bloodstream may help for blood and lymphatic cancers. Like chemotherapy and radiotherapy, there have been mixed results for this treatment.

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The next pillar of cancer therapy

Chimeric Antigen Receptor

TUMOR-MELTING T CELLS T CELL

Tumor regressions observed in Phase 1/2 clinical trials for patients with B-cell cancers after infusion of CAR (Chimeric Antigen Receptor) T cells engineered at Fred Hutch.

Before CAR-T cells

Day 29 after CAR-T cells

Regression of Mantle Cell Lymphoma Involving the Stomach

Before CAR-T cells

Schematic of a CAR-T cell

Day 32 after CAR-T cells

Regression of Diffuse B Cell Lymphoma

Scapular lesion

Para-aortic tumor Retroperitoneal Iliac tumor

Before CAR-T cells

Day 30 after CAR-T cells

Day 60 after CAR-T cells

Regression of B Cell Lymphoma Involving the Kidney

Before CAR-T cells Day 31 after CAR-T cells

Regression of Extramedullary Acute Leukemia

Bone Marrow (Before CAR-T cells)

83.6% blasts Bone Marrow (Day 28 after CAR-T cells)

Before CAR-T cells

Day 37 after CAR-T cells

Complete remission

Regression of Advanced Acute Leukemia Involving Bone Marrow and Kidneys Source: Riddell, Turtle and Maloney Labs, Fred Hutchinson Cancer Research Center

The StethoSCOOP | Spring 2016

Riddell and his colleagues used the immune system in a different way. They tried to deliberately turn their patients’ immune systems against their cancers, having immune cells target and destroy the cancers directly.

The trial began in 2013 with patients who were months from death, whose cancers were especially resistant to any prior treatment and had metastasized to other parts of the body.

Riddell proposed the removal and reprograming of a patient’s T-cells, genetically reengineering them with synthetic molecules called chimeric antigen receptors (CARs). These modifications enabled the T-cells to “seek out and recognize and destroy the patient’s tumor cells,” Riddell said. Typically, T-cells act like bombs, destroying foreign cells by exploding on impact. But they need to recognize the invaders first, and normal T-cells have difficulty identifying cancer cells.

Modifying T-cells with CARs enabled them to detect and destroy a particular target cancer cell identity that normal T-cells would not have recognized. Using this method, Riddell and his colleagues were able to send 27 of 29 terminal patients with acute lymphoblastic leukemia and 19 of 30 patients with non-Hodgkin’s lymphoma into full and sustained remission.

This kind of immunotherapy is advantageous not only because of its high success rate, as it reversed the condition of terminally ill patients, but also because it only needs to be administered once. T-cells can multiply on their own once they enter the human body. This means that unlike chemotherapy and radiotherapy, infamous for their long, drawn-out processes, T-cell modification never needs to be re-administered. Chemotherapy and radiotherapy also put patients out of work for months and damage other cells in the body. But the new T-cell therapy, if it works, has the advantage of acting faster and killing cancer cells while inflicting less damage on healthy ones.

much like chemotherapy and radiotherapy, it’s not going to be a save-all.” Seven of the patients developed cytokine release syndrome, a lifethreatening blood toxicity that often accompanies an overdose of antibiotics. Although 27 of the 29 patients with acute lymphoblastic leukemia went into full remission, the remaining two patients died from poisoned bloodstreams. Riddell and his colleagues also did not publish their data, which has led some to some skepticism among other researchers.

The T-cell modification therapy is fast acting, but it has the potential to make patients sick with other life threatening conditions like cytokine release syndrome. Its overall effect on the body, while shorter-lasting, is still more detrimental than those of chemotherapy and radiotherapy.

Both traditional treatments can cause nerve damage, muscular atrophy, and blood disorders, but their side-effects are not as immediately life threatening. Moreover, many cancers of the bloodstream and lymphatic systems are diagnosed early on because they show early symptoms. In these cases, chemotherapy and radiotherapy are very effective. Only in advanced stages of the disease do chemotherapy and radiotherapy show mixed results.

In this regard, modifying T-cells is a therapy that works as a last resort when a patient is terminal. But it should not be used if the cancer is responsive to the more traditional forms of treatment. Since Riddell’s study was released, it has been controversial in the cancer research community, but members of other health organizations and media publications remain optimistic. The health editor of the BBC news website James Gallagher mentioned that, “the field of immunotherapy... is coming of age.” Only time and more extensive research will determine the true effectiveness of the immunotherapy alternative.

This treatment looks reassuring, but it has drawbacks. Riddell mentioned that although it may serve as a “new pillar of cancer therapy...

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Th e Dangers of Ex cessi v e Sugar I ntak e

By Klaudio Haxhillari

The StethoSCOOP | Spring 2016

M any people ar e aw ar e that excessive sugar intake can har m the hum an body, but just how har m ful can its effects be? How m any people know w hat the r ecom m ended daily am ount of sugar intake is? Unfor tunately, m any ar e unaw ar e of the adver se effects that excess sugar consum ption has, other than w eight gain, and m ost people do not know w hat the r ecom m ended value of added sugar s is. A w ay to solve this issue is by infor m ing the public about the danger s of unhealthy eating habits and by offer ing advice that pr om otes healthy eating habits.

The Am er ican Hear t Association r ecom m ends that people lim it the am ount of added sugar intake to about 6 teaspoons of sugar for m ost w om en and 9 teaspoons for m ost m en.

For com par ison, a single 12 ounce can of soda contains appr oxim ately 8 to 9 teaspoons of added sugar (AHA). A can of soda is close to, if not alr eady exceeds, the lim it for the safe am ount of daily sugar intake. This should r aise an alar m ing concer n to m ost people but the lack of this know ledge in the gener al population has pr evented this fr om occur r ing.

Consum ing sugar above the Am er ican Hear t Association suggested lim it is danger ous because of the deleter ious health effects associated w ith high levels of sugar intake.

Excessive sugar intake has been linked to sever al diseases such as hear t disease, liver disease, hyper glycem ia, and dental pr oblem s. A study found that people w ho intake 25% or m or e of their daily calor ies fr om sugar ar e alm ost thr ee tim es m or e likely to die fr om hear t disease than those w ho consum ed less than 10% of added sugar in their diet (Yang et al., 2014). Too m uch added sugar can also cause fatty buildup in the liver , w hich can lead to liver disease.

Fur ther m or e, r esear ch has show n that excessive sugar intake is linked to diabetes and obesity.

Lastly, sugar causes dental pr oblem s by pr oducing a "sticky substance" that allow s bacter ia, w hich use sugar as an ener gy sour ce, to stick m or e easily to teeth.

The pr olifer ation of high sugar foods in Am er ican society encour ages an unhealthy diet am ong m any people. Par ents m ay pur chase high sugar content foods for their childr en because they ar e unaw ar e of the danger s to their childr en?s health. This cr eates an unhealthy eating habit that w ill be difficult to br eak at an

older age. Unhealthy eating can im pact people as young adults too, even if they had healthy eating habits dur ing their childhood. For exam ple, students on college cam puses ar e constantly exposed to sugar in dining halls. W her eas par ents m ay have had a lar ge say in the food supply of the household, the situation does not per tain to students at college. Incom ing fr eshm en face m uch m or e than w eight gain or the ?Fr eshm an 15?; they ar e exposed to a vast supply of food in the dining halls and an unr estr icted access to high sugar foods. The unlim ited r efills at the soda station and the plentiful access of desser ts at all tim es have left students w ith a new sense of fr eedom w ith danger ous options.

Sadly, the aver age sugar intake in the United States is excessive and continues to r ise (USDA, 2002). This is due to the population cur r ently having m or e access to fast food r estaur ants than pr evious gener ations. Fast food r estaur ants w ill claim that their food options ar e becom ing healthier , but this is m er ely an attem pt to incr ease their pr ofits. The gr eed for pr ofit is the sam e r eason that they do not sw itch to healthier foods: they ar e able to m ake m or e m oney off of the num er ous custom er s w ith poor eating habits.

The task of r educing one?s sugar intake is not easy, but ther e ar e som e helpful w ays to ease the pr ocess. One w ay for people to r educe their added sugar consum ption is by r eceiving their sugar intake fr om natur al sugar s found in fr uits.

Fr uits pr ovide a r ich sour ce of vitam ins, m iner als, and antioxidants to keep people healthy and ener gized. Ther efor e, by consum ing fr uits Am er ica?s sw eet tooth can be fulfilled in a less har m ful w ay.

One can also im pr ove their diet by taking high sugar content foods and dr inks off their shopping list. Opening the fr idge w hen one is hungr y and seeing a car ton of ice cr eam w ill m ake it extr em ely tem pting to eat it. How ever , if one?s food stor age contains healthy item s, that per son w ill instead consum e the healthy item s pr esent in the fr idge. The idea her e is sim ple: change your eating habits by changing the contents of your fr idge.

W hile diet adjustm ents m ay help the individual, the best w ay to r educe excess sugar consum ption acr oss the countr y is thr ough education. The m or e know ledgeable the

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Am er ican population becom es about the detr im ental effects of sugar , the gr eater chance that people w ill be m or e conscientious of their sugar consum ption. A w ay to incr ease aw ar eness is by pr oviding consum er s w ith quantitative data on sugar consum ption. People m ay under stand conceptually that excess sugar is detr im ental to their health, but w ithout concr ete num ber s, m any people ar e oblivious to their sugar consum ption and pay little attention. Thus, education is key in helping to r educe this pr oblem . The em phasis on nutr ition facts and labels is par ticular ly im por tant. Fr equently,

these labels ar e not r ead by the consum er so it is cr ucial to get m or e people to r ead and under stand the labels m or e often. The nutr ition labels give insight into w hat a par ticular food item contains so that one can m onitor and eat substances like sugar in m oder ation.

M aking an attem pt to m onitor your sugar consum ption and diet is highly encour aged. It is im por tant for ever yone to becom e m or e educated on the r isks of excessive sugar intake and it is r ecom m ended that you spr ead this aw ar eness to other s.

Happy healthy eating!

The StethoSCOOP | Spring 2016

UTERINE TRANSPLANTS

A New and Controversial Form of Organ Donation

by JUNE XIA ABOVE: Surgeons performing first U.S. uterine transplant at Cleveland Clinic.

IMAGE CREDIT: Cleveland Clinic

Transplants are a life-saving operation: they offer a second chance at a life that may have otherwise ended far too soon. However, what if a transplant, rather than prolonging a life, actually led to the creation of one? With the advent of uterine transplants, this idea no longer remains just a possibility, but has become a reality in recent years. There are a variety of reasons why women may want to partake in such a surgery; some have suffered complications related to cancer or other diseases, while other women were born without a uterus altogether, a condition known as Mayer Rokitansky Kuster Hauser syndrome (MRKH). Uterine transplants provide the option of bearing biological children in vivo for women, and if American 33

doctors were able to successfully perform these transplants, there would be as many as 50,000 potential candidates in the U.S. to undergo such a surgery. While the development of such a transplant marks a remarkable medical breakthrough, it comes with a hefty number of considerations, both practical and ethical. In addition to the numerous health risks the recipient faces, from infection to rejection of the transplanted uterus, is such an operation pragmatic when there are many other options available for starting a family?

More broadly, should the medical community invest so much time and money on such a specific surgery when the resources could be dedicated to more widespread, pressing diseases such as cancer? Such questions, and many more, are being debated within the medical community, and increasingly in the general public, following the first successful transplants in the U.S. this past March at the Cleveland Clinic in Ohio.

(top) Andreas Tzakis, MD, PhD, Lead Transplant Surgeon at Cleveland Clinic.

IMAGE CREDIT: Cleveland Clinic

(bottom) Mats BrännstrÜm, Professor/ chief physician at University of Gothenburg.

IMAGE CREDIT: University of Gothenburg

The idea of uterine transplants was first proposed in 1998 by a cervical cancer survivor whose uterus was removed due to the cancer, but still possessed her ovaries, egg cells, and the proper hormones required for pregnancy. When the patient suggested the idea of acquiring a uterus, her doctor, Dr. Mats Brannstrom of the University of Gothenburg, was shocked. However, after deliberation with his colleagues, along with the occurrence of other medical transplant breakthroughs around the same time, Dr. Brannstrom began to see real potential in uterine transplants.

More than a decade later, in September of 2012, Dr. Brannstrom and his research team, performed the first successful uterine transplants on two Swedish women, both of whom were in their 30s. Of the two, one gave birth to the first baby born via uterine transplant in October 2014.

Like with all organ transplants, uterus recipients have to be carefully monitored and take a variety of drugs after the operation to prevent infection and ensure that their bodies accept the uterus.

Failure to do so may result in blood clots, amongst other complications, that would require the uterus to be removed, resulting in additional intensive surgery. However, unlike other transplants that are usually permanent, the uterus is removed after the recipient has carried one to two children to prevent possible long-term damage.

The uterus may be taken from either a deceased donor or a living donor. In fact, because the recipient’s body has the best chance of accepting the uterus if it comes from a close relative, more than half of the successful uterine transplants that have been performed so far are those in which the uterus donor is the mother of the recipient. For future babies born via these temporary uteruses, the case may very well be that they were carried in the same uterus

The StethoSCOOP | Spring 2016

that once carried their mothers. While this thought would strike most us today as unfamiliar, the families who do undergo such an experience will create a unique bond across three generations in a way unlike any before.

Many people may wonder why a woman would volunteer to go through this procedure to experience pregnancy, another physically grueling experience. As Dr. Eric Kodish, the director of the Cleveland Clinic’s ethics center, explains, “when organ transplantation started more than 50 years ago, the goal was purely to save lives, but has broadened to include improving quality of life, with for example, face and hand transplants.” For women who, under normal circumstances, would not be able to become pregnant, providing this opportunity for a uterine transplant means giving them the chance to experience something deeply intimate. One of the volunteers who underwent screening at the Cleveland Clinic to be a potential uterus recipient revealed that she “crave[s] that experience. [She] want[s] the morning sickness, the backaches, the feet swelling. [She] want[s] to feel the baby move. That is something [she’s] wanted for as long as [she] can remember.”

One of the main criticisms against uterine transplants argues that the amount of time and money (up to hundreds of thousands of dollars) being put into research for a transplant targeting only a specific group of the population could be better spent on making advances in research for diseases that will have a much wider impact.

Others point out that uterine transplants, which have a high risk of failure and is still in the early stages of experimentation, are not the only option for women desire biological children, with another well known option being gestational carriers, or surrogate mothers. In many cases, the surrogate and the biological mother may be close relatives, and the “experience [brings] out the best in these families, with so much love and compassion in the utmost act of giving.”

Regardless of what women lacking uteruses choose when it comes time to have children, bearing a child means a great deal to them and they are willing to go to great, and often costly, lengths to achieve it. Some may choose the uterine transplant for personal reasons related to cultural practices or religious beliefs, and others may opt for adoption or surrogacy. Beyond the decisions individual women make regarding having children, uterine transplants can be viewed in a broader context within the medical field and appreciated for what it represents: a tremendous advancement in fertility and reproductive science that may have great implications for future research and operations.

35

The Science of

Indecisiveness & Decision-Making

by KAELYNN WORKMAN

Imagine this—you and a friend believe that you guys are on the edge of a technological breakthrough. You have a dream of starting a company.

A company that will be based on the success of a product that is largely ignored and underestimated by everyone, except for a few people. However, you both see its potential and you know that the success of your future company will require that full stock and effort is put forth right now, before someone else changes the field of the game.

However, there is a slight problem—you are a full time student pursuing your bachelor degree at a prominent university and being a full time student greatly limits your ability to fully invest yourself in the startup of this company. So what do you decide? Do you stay and finish your degree and follow a path that is sure, straight and narrow or do you follow your dreams and passion? The person who had to make this decision followed

his passion and sparked a computer revolution by turning the computer industry on its head through the development of Microsoft.

Now think about a hard decision that you will have to make in your near future. How will you decide between the two options if both options seem equal in value or you are unable to determine the relative value of each option? How will you navigate between a rock and a hard place?

The way the human mind makes decisions is based on two networks—the cognitive control network and the value based decision making network, both of which depend on different regions in the prefrontal cortex (Szalavitz, 2012). The valuation network is largely situated in the ventromedial prefrontal cortex but also includes the orbitofrontal and frontopolar cortex (Szalavitz, 2012). This network provides us with information about objects or ideas that are pleasurable and rewarding,

The StethoSCOOP | Spring 2016

while also determining if the relative pleasure of pursuing an object or idea is greater than its relative risk, thereby allowing a decision to be made regarding if that object or idea should be pursued.

People who often choose immediate over delayed gratification or have difficulty assessing the riskiness of various options, generally show reduced activity in this region or suffer from damage in this region. Thus, the valuation network serves to distract the brain from clear, defined goals and provides us with emotional responses to objects that are enjoyable, valuable and are believed to provide us with greater overall gratification in the future by weighing perceived risk versus perceived reward.

In fact, emotions are so vital to the way the human mind makes decisions that people who are unable to experience emotions have difficulty choosing one thing over the other because of the

lack of surprise, anger, happiness or excitement one would usually feel when making a satisfying or less than satisfying decision. A study done by neuroscientist Dr. Antonio Damasio in the 1990’s supported this fact. Dr. Damasio studied patients who had sustained damage in the amygdala, the part of the brain where emotions are generated.

When these patients were given options between two choices, even very mundane decisions like deciding on what to eat became as laborious and agonizing a task as choosing a career would be for people with emotions. Why? This is due to the reliance of preference-based decisions on emotions and the ability to feel what makes you happier when choosing something else over another.

Without a rational way to decide between which object will make them happier, people must rely on their emotions to guide their decision-making.

Thus, the patients who were unable to feel emo37

tions could never decide in preference-based decision-making because both options felt equally the same (Bechara, 2000, p.301). This phenomenon was described when a patient of Dr. Damasio was unable to decide between two different dates for an appointment. “If I come next Tuesday, I’ll have to cancel my lunch with Fred. If I come next Wednesday, I’ll have to get up early to catch the bus” (Schacter, 2014, p.331). Due to his inability to feel any emotion (negative or positive) when he thought about the two options, he was left unable to decide between the two appointment dates.

This shows that while the amygdala functions to provide us with emotion, the ventromedial cortex functions to help us re-experience an emotion that was linked to a particular event, once that event is recalled (Bechara, 2000, p.301).

Furthermore, researchers at the University of Zurich who were further interested in how preference-based indecision manifests itself, conducted a study using transcranial magnetic stimulation (TMS), in which the communicative flow between areas of the brain were disrupted while patients were given the task of making a decision. The researchers discovered that the stability and precision of choices depends on the strength of the communication between two areas of the brain—the ventromedial prefrontal cortex (which houses the valuation network) and the parietal cortex (which aides in spatial orientation and action planning) (University of Zurich, 2015).

This finding was important because it revealed that it wasn’t just the activity of certain brain areas that played a role in decision-making, but it was also the intensity of the communication between different brain areas. When the intensity of communication was decreased by TMS, preference-based decisions were shown to be less stable, resulting in indecisiveness.

However, intensifying communication between the ventromedial cortex and the parietal cortex did not increase the stability of preference-based decisions (University of Zurich, 2015).

While the valuation network may divert our attentions to a sundry of features, factors and

objects, the second network which aides in decision making is the cognitive control network and it functions to keep us focused and resolute on our desired goals. The cognitive control network is situated in the dorsolateral prefrontal cortex, which maintains communication with the anterior cingulate cortex to facilitate making a focused and defined decision and also finding possible erroneous or astray and irrelevant options and eliminating them. The cognitive control network therefore aids in choosing the correct and goal-oriented option, between multiple options, when the decision is directed towards a specific and distinct goal (Bergland, 2015). Damage to this area would indicate an inability to make clear and determined decisions, which explains why people who are often distracted easily and display an inability to maintain focus while switching between multiple tasks display reduced activity in the dorsolateral prefrontal cortex. Both the valuation and cognitive control networks work together to determine what decisions you should make, and what decisions will offer the best overall value in the longrun. When either of these networks are impaired, indecisiveness manifests itself in many different forms, ranging from mild to extreme.

With the most cutting edge research currently being performed to determine how decisions are made, researchers and scientists are hoping to advance this field to determine how, when and why the decision making process goes awry in order to aide in the understanding of many psychological disorders that are inherently decision-based.

These include psychological disorders like depression, addiction, and eating disorders.

With the continued success of psychological and brain science research, one day we will be able to understand many of the decisions that we make and why they more often than not leave us perplexed and second-guessing ourselves. We will be able to understand why, when given the option of pursuing a passion in starting a business in software and finishing a bachelor degree at Harvard, some people choose Harvard, and others choose to startup Microsoft.

Transcat het er Aort ic Val ve Repl acement : A Novel Devel opment f or Less Invasive Surgical Procedures

By Kevin Hui

In an age of r apid m edical and scientific advancem ent, car diovascular issues still r em ain as one of the m ost pr evalent sym ptom s of disease in the United States.

In 2013 alone, appr oxim ately 11.5% of adults in the US w er e diagnosed w ith som e for m of car diovascular disease, and it r em ains the leading cause of death in Am er ica, w ith one in four deaths being associated w ith hear t disease1. One of the m ost com m on for m s of car diovascular disease in the elder ly population affects the valves of the hear t.

The m ost devastating for m of valve disease ar ises fr om aor tic stenosis, in w hich the aor tic valve becom es unable to open fully. The aor tic valve, w hich contr ols the flow of blood fr om the left ventr icle of the hear t to the aor ta, is cr itical in the deliver y of oxygenated blood to the r est of the body. Its br eakdow n can lead to intense str ain on the hear t as w ell as insufficient blood flow to the br ain and the r est of the body 2. Though aor tic

stenosis m ay be pr esent congenitally, the pr edom inant num ber of patients affected ar e elder ly.

In fact, aor tic stenosis affects appr oxim ately 5% of the elder ly population in the United States3. This pr oposes a com plex issue: hear t sur ger y is the classic r esponse to such a disease, how ever m ost elder ly patients ar e sim ply too fr ail or w eak to sur vive the str esses of open hear t sur ger y. All tr aditional hear t sur ger y pr ocedur es involve an incision thr ough the br eastbone in or der to expose the hear t for oper ation. Such an invasive pr ocedur e can lead to incr eased chances of chest infection, sw elling, fever , and inflam m ation 4. Fur ther m or e, hear t sur ger y typically r equir es stopping the hear t and placing the patient on a hear t/lung m achine, w hich contr ols br eathing and blood cir culation for the dur ation of the pr ocedur e. Though the hear t/lung m achine is essential for hear t sur ger y, it also incr eases the r isk of str oke and m em or y 39

loss in patients4. For elder ly patients, these r isks tr anslate into a 5% incr ease of in-hospital m or tality after car diac sur ger y w hen com par ed to younger patients5, as elder ly patients ar e m or e susceptible to adver se health conditions due to advanced age. Clear ly, a less invasive m ethod is r equir ed.

Enter the Tr anscatheter Aor tic Valve Replacem ent (TAVR) pr ocedur e, a less invasive ther apeutic option for tr eatm ent of aor tic stenosis. The TAVR pr ocedur e allow s sur geons to per for m valve r eplacem ent sur ger y w ithout the need for open hear t sur ger y or car diopulm onar y bypass7. The pr em ise of the pr ocedur e, as the nam e suggests, involves the im plantation of a pr osthetic valve thr ough the use of a catheter. A catheter is a thin tube that, w hen inser ted into a body cavity, duct or vessel, can ser ve a w ide var iety of functions. These functions can include the adm inistr ation of fluids to cer tain par ts of the body or a w ay for sur gical m ater ials to r each inner par ts of the body. In the TAVR pr ocedur e, the catheter pr im ar ily ser ves as an access point to the hear t valve of inter est. The catheter can r each the hear t valve thr ough a num ber of possible m ajor ar ter ial system s, including the fem or al ar ter y (found in the thigh), the subclavian ar ter y (found under neath the collar bone), or dir ectly thr ough the aor ta itself 7.

All these entr y points r equir e only a sm all incision, as the catheter 's w idth is r elatively sm all (about the thickness of a standar d headphone jack cor d).

But once inside, how w ould the sur geon know w her e they ar e going? Unlike an open hear t oper ation, w her e the sur geon can dir ectly see the site of oper ation, the TAVR pr ocedur e utilizes fluor oscopy to visualize the oper ation. A fluor oscopy, or angiogr am , is an x-r ay test that uses a special dye and a cam er a to visualize blood flow in the ar ter ies thr ough the use of a catheter 8. The cam er a sits over head the patient, and is able to captur e video and im ages using x-r ays in r eal tim e, allow ing the sur geon to see exactly w her e the catheter is being dir ected.

Once situated in the ar ter y of inter est, the catheter is used to adm inister a dye as a contr ast m ater ial, so that the flow of blood in the ar ea can be clear ly visualized by the cam er a9. W hen utilizing fluor oscopy to visualize the hear t valve of a patient suffer ing fr om aor tic stenosis, the dye w ould tr avel w ith the flow of blood, allow ing the sur geon to visualize the decr eased blood flow thr ough the valve char acter istic of aor tic

stenosis.

As r eplacem ent of the defective aor tic valve r equir es the use of the catheter to deliver the new pr osthetic valve into the r ight place, m anipulation and usage of the catheter becom es a cr itical par t of the success of the TAVR. The deliver y system itself follow s a r ather ingenious design. A balloon catheter , a special type of catheter that contains an inflatable "balloon" at the tip of the catheter , is used to deploy a pr osthetic valve over the defective hear t valve.

Initially, the balloon at the tip of the catheter is deflated in or der to r em ain thin enough to m ove into the cor r ect position. Ar ound the balloon tip, ther e a stent (a m etal m esh tube used to suppor t w eak ar ter ies9) containing the pr osthetic valve r eplacem ent 10. The stent is w r apped tightly ar ound the balloon of the catheter , allow ing for easy m ovem ent. Once the catheter is positioned at the aor tic valve and the sur geon is r eady to deploy the r eplacem ent valve, the balloon of the catheter is expanded, w hich in tur n expands the stent and the pr osthetic r eplacem ent valve over the defective valve10. Once the r eplacem ent valve is secur ed in place, the sur geon can then test the effectiveness of the r eplacem ent valve w ith fluor oscopy, using the dye to visualize if the new valve helped incr ease blood flow thr ough the ar ea to healthy levels. W hen the pr ocedur e is com plete, the sur geon sim ply needs to r em ove the catheter and close the incision m ade upon entr y.

W ith the incr ease in popular ity of the TAVR pr ocedur e over the last decade, it com es to no sur pr ise as to w hy sur geons and patients ar e pr efer r ing this less invasive m ethod of tr eatm ent. It has becom e the standar d of car e for patients w ho ar e not candidates for open sur ger y, w ith over 50,000 TAVR pr ocedur es having been per for m ed in the past decade in over 40 countr ies11.

Studies per for m ed com par ing the health of patients after tr aditional hear t valve r eplacem ent sur ger y and that of patients after the TAVR pr ocedur e only confir m the efficacy of the pr ocedur e.

Studies dem onstr ate that TAVR patients had a 15% higher chance of sur vival after one year as com par ed to those under w ent open hear t valve r eplacem ent 7. As the tr end tow ar ds less invasive m edical pr ocedur es becom es incr easingly pr om inent in the m edical com m unity, the TAVR can count itself as one of the m any effective novel pr ocedur es used to gr eatly im pr ove the quality of patient car e ar ound the globe.

The StethoSCOOP | Spring 2016

41

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The Danger s of Excessive Sugar Intake

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New Im m unother apy Tr eatm ents for Bloodstr eam Cancer s is a New ?Baby Step?

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The Science of Indecisiveness and Decision-M aking

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