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Biomedical Odyssey

Life at the Johns Hopkins School of Medicine

residency interviews

Applying for Residency: Interview Season

The last time I wrote about applying to residency, fourth-year medical students were just about to hit the submit button on the Electronic Residency Application System. Several long weeks later, the interview season has begun.

The irony of the phrase “hurry up and wait” becomes acutely painful for students during the weeks between submitting residency applications and receiving interview invitations. Applying for residency is much like applying for a job — you put together a CV, send it out to several prospective employers and hope that they are interested enough to invite you for an interview. For the past several weeks, fourth-year medical students have been eagerly waiting for those interview invitations and, after receiving them, have been busy scheduling flights, booking hotels and preparing to explain why they are an excellent fit for each program.

However, before the craziness of scheduling interviews — which requires students to strategically accept the maximum number of interviews, while allowing for adequate time to travel between cities — there is the wait. Thanks to peers applying to the same specialty and websites such as Student Doctor Network, students know almost immediately when their dream schools start sending out invitations — and are in for an unpleasant moment if they do not receive one. Thus commences the anxious wondering: Will there be a second round of interview invitations? Why did I not get invited in the first round? Is there anything I can do or say to the program to garner one of those coveted invitations? By the time I get an invitation, are there going to be any interview spots left? Unfortunately, there are no satisfactory, cut-and-dried answers to any of these questions.

By and large, though, most students will receive or have already received invitations to interview at their dream schools, and indeed, many are now weeks into the interview process. Aside from the nervousness that accompanies each interview, there is also an underlying hum of enthusiasm and excitement. The attendings and residents at each program are potential mentors; the other interviewees, future colleagues, or perhaps even future co-residents. At each interview, there is a tantalizing glimpse into the world that everyone has worked so hard during medical school to have the privilege to enter. Additionally, each interview allows the applicant a peek at how that specific program’s rounds work, what the hospital culture is like and what the program values. Similarly, programs use the interview process to find applicants with aligned goals who they think will not only learn from their institution, but also thrive in their particular environment and form part of a cohesive team.

The past few weeks have been both exciting and trying, filled with emotional highs and lows. Charles Dickens once penned, “It was the best of times, it was the worst of times …” While he was referring to London and Paris during the tumultuous French Revolution, somehow, it resonates well with this part of the application process to residency.

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human head puzzle

At the Vanguard of the Psychedelic Renaissance

A priest, a minister and a rabbi walk into Johns Hopkins Bayview Medical Center to ingest psilocybin, the active ingredient in hallucinogenic mushrooms. Although this probably sounds like the beginning of a great joke, new advancements in the field of psychedelic medicine are no laughing matter.

After nearly 50 years of prohibition, academic studies and clinical trials have recently begun to examine illegal and psychedelic drugs as treatment tools for a variety of physiological and psychological conditions. Of these, marijuana has been at the forefront, based on growing evidence of its beneficial applications as a treatment for diverse pathologies, including glaucoma, seizures and chronic pain. This has led to an increased acceptance of the plant in the medical pharmacopeia, and indeed, its legalization for medical use has increased from four to 25 states since 2000. Similarly, ketamine, a dissociative anesthetic conventionally used in veterinary medicine, has shown remarkable efficacy in recent trials for treating depression. The psychoactive compound MDMA, or Ecstasy, is being utilized in conjunction with psychotherapy to treat patients with post-traumatic stress disorder, with remarkable results. The success of this combination has been so dramatic that the Food and Drug Administration recently fast-tracked the MDMA-assisted psychotherapy phase III clinical trials that are already underway in hopes of determining an acceptable medical use of the drug by 2021.

This recent resurgence in psychedelic studies is exciting but not necessarily surprising for two researchers at Johns Hopkins Bayview. Roland Griffiths and Matthew Johnson have been examining the powerful effects of psilocybin in a variety of contexts for over a decade, and both are optimistic about its future applications as an accepted pharmaceutical. In collaboration with a small group of researchers from several universities around the world, Griffiths and Johnson have demonstrated that psilocybin-assisted psychotherapy can help induce and maintain behavioral changes, such as quitting nicotine or cocaine, as well as psychological changes, including reduction in depression symptoms and end-of-life anxiety associated with terminal cancers. In both cases, preliminary trials have demonstrated efficacy rates over 80 percent, which were maintained for at least one year.

The first psilocybin study Griffiths completed in 2006 examined the concept of the “mystical experience” in volunteers. The majority of study participants experienced significant feelings of “unity ... an interconnectedness of all things ... sacredness of life,” and over 60 percent reported it as the most meaningful experience of their lives. In further studies, Griffiths showed a consistent correlation between individuals’ self-reporting of this mystical experience and the success of their treatment. Strikingly, those with the most success quitting smoking or resolving symptoms of depression all reported high levels of this mystical aspect. To better understand this phenomena, Griffiths and Johnson are now recruiting religious leaders to engage in a study where they will use psilocybin in a therapeutic setting and report exclusively on its effects to their own deeply held beliefs. Griffiths believes the benefit will be twofold: These participants will be better able to communicate the mystical experience to researchers, and may also enrich their own congregation and vocation in a new and powerful way.

Psychedelic researchers are quick to distinguish that these positive effects in clinical settings do not mean the drugs are suddenly safe to use by anyone, anytime. Instead, they advocate strongly for controlled consumption, with a well-trained clinician guiding the patient through the experience to highlight positive growth and outcomes.

Originally made illegal during the Nixon administration, psychedelics have been placed on the Schedule I list for having “no medicinal value” for nearly 50 years. But as a remarkable body of evidence to the contrary is collected by researchers like Griffiths and Johnson, the country must begin to more seriously discuss how to best incorporate these substances into the medical field so their positive effects may reach the patients who need them.

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doctor listens to fetal heartbeat on pregnant belly

More Training Means More Residents Meet Their Match

Matching into residency was one of the greatest days of my life. Years of hard work and dedication had finally culminated into the opportunity to become a doctor and practice medicine where I wanted, and in the specialty where I fit best. A few years into being a resident, the process started over, with the fellowship application process. In almost every field of medicine, there are opportunities to subspecialize, and fellowships are one such opportunity.

Fellowships are a way for residents to specialize in a specific area of medicine or surgery.  For example, if an internal medicine resident wants to become a cardiologist, he or she typically has to complete three years of residency, followed by three years of fellowship in cardiology. The same applies for other subspecialties — a pediatric resident who wants to specialize in taking care of sick neonates in the ICU would complete a neonatal ICU fellowship.

Over the summer, I had the opportunity to travel around the country with some of my greatest friends and colleagues within the Johns Hopkins Department of Gynecology and Obstetrics as we interviewed for fellowship positions in four different specialties: gynecologic oncology, maternal-fetal medicine, reproductive endocrinology and infertility, and urogynecology. Cumulatively, we received over 100 interviews. This fall, we met out matches and will be traveling far and wide to fulfill our dreams.

Typically, gynecology and obstetric residents either decide to subspecialize in a fellowship or continue their career as a general Gyn/Ob. In a study looking at residents who chose to subspecialize, data from 2012 showed that around 20 percent of residents apply for fellowship. Considering seven of Johns Hopkins’ nine residents applied for fellowship and 100 percent matched for competitive fellowship with acceptance rates averaging about 69 percent, we matched very well this year!

Diana Cholakian with her resident friends in the Johns Hopkins Department of Gynecology and Obstetrics
Diana Cholakian with her resident friends in the Johns Hopkins Department of Gynecology and Obstetrics

Although my colleagues and I applied for a variety of subspecialties at many different institutions, in reflecting on why we each chose a specific career path, three things were consistent.  We picked these specialties because of the “patients, procedures and problems,” and the way our careers will allow us to interact with and influence all three.

Ultimately, I chose to become a gynecologic oncologist because I love the patients, the procedures are inspiring, and the problems presented in treating their illness are challenging and complex. The fact that all of the residents and one fellow who applied into these subspecialties were placed in competitive fellowships is a testament to the success of the Johns Hopkins residency program in training future gynecologists and obstetricians.

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patient lying in the hospital bed

The Problem of Delirium in the Intensive Care Unit

In cardiac surgery, most patients come out of the operating room still heavily sedated and intubated — a tube down their windpipe helps them breathe, one is in their bladder so they don’t need to urinate and multiple others protrude from their chest, draining blood-tinged fluid. Some patients exit surgery actively “paced,” with several wires on the surface of their heart urging it forward at a steady rhythm somewhere between 90 and 100 beats per minute. The first six hours after open-heart surgery are crucial, so patients are quickly wheeled from the operating room to the cardiovascular surgical ICU — also known as the CVSICU — where they are closely monitored during this critical recovery period.

As you might imagine, the CVSICU can be overwhelming for patients’ loved ones and the patients themselves. As they are gradually weaned off sedating medications, patients often awake to a choking sensation from the breathing tube forcefully blowing oxygenated air into their lungs. One family member once mentioned that the scariest part for their loved one wasn’t the thought of having his sternum split open by a bone saw to expose his heart for surgery; he was most afraid of waking up on a ventilator. Thankfully, for most patients, “wake, wean and extubate” is the typical plan for post-surgical recovery. As their sedatives are reduced, most patients can understand and follow commands, and are able to easily have the tube removed and breathe on their own.

All fourth-year medical students at Johns Hopkins undergo a one-month rotation in critical care to better understand and learn how to care for complex patients. Over the last month, I was intimately involved in the care of several patients whose post-recovery plans required extra time on the ventilator during my rotation in the CVSICU. A few of these patients experienced a phenomenon called ICU delirium. Delirium refers to a state of altered thinking and consciousness that can occur in the critically ill patient. Patients often become confused, disoriented and agitated following a major surgery or while recovering from trauma. In such cases, delirium can induce an altered state of reality, as the sounds and sights of the ICU interact with the patient’s own thoughts to create terrifying and bizarre illusions. Because of the instability and agitation that often coincide with ICU delirium, these patients are kept on the ventilator for longer to protect their airways and support breathing.

“She wasn’t herself,” said one family member as she reflected on her mother’s ICU stay. “At first, it looked like she was getting worse instead of better.”

Delirium is associated with psychological distress, such as PTSD, and poor health outcomes, including longer ICU stays and higher rates of mortality. Therefore, it is critical that CVSICU staff members be especially vigilant in monitoring and treating delirium. Indeed, one study from 2010 found that over 80 percent of patients on ventilators at a particular institution experienced ICU delirium. Johns Hopkins is taking steps to find better ways to treat and support patients who go through delirium in the ICU, including orienting patients to a day-night cycle with natural light, using sedating medicines sparingly and monitoring patients’ mental states post-surgery using delirium screening tools. By combining psychological and physical rehabilitation and supporting patients throughout the recovery process, it is the hope of researchers that the incidences of ICU delirium can be reduced to improve patient outcomes.

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doctor showing her patient a test result on a tablet at the bedside

Implementing Precision Medicine in an Academic Hospital

Precision medicine, or personalized medicine, is a growing field that uses big data to treat the individual patient. It uses tools such as DNA sequencing and bioinformatics to ask, “What are the individual characteristics of my patient?” — for example, in her genetic makeup, environment or in the mutation profile of her tumor — and then examines whether this information can be incorporated into medical decision-making. With President Obama’s 2015 Precision Medicine Initiative, the United States government has launched a multimillion-dollar investment in supporting precision medicine.

One of the leaders in this field is Dan Roden, who currently serves as the vice president for personalized medicine at Vanderbilt University. On Oct. 5, Roden gave the 2016 Sir Henry Hallett Dale Memorial Lecture at The Johns Hopkins University in a talk titled “Engineering a Healthcare System for Discovery and Implementation in Precision Medicine.”

Tailoring disease prognoses or choice of drug treatment to the individual patient is not a new concept, and Roden began by giving several examples of how patients’ genetic makeup is already being used to predict their risk of drug side effects. One such drug is procainamide, which is prescribed to treat cardiac arrhythmias. Liver enzymes modify the chemical structure of procainamide in a process called acetylation. People who have a genetic deficiency in these enzymes are called slow acetylators, whereas those with a gene that instead confers strong enzyme activity are called rapid acetylators. Since the 1970s, it has been known that slow acetylators who use procainamide have an increased risk of developing a lupuslike side effect called drug-induced lupus erythematosus. Although procainamide is not a commonly prescribed medication, knowledge of acetylation status could help doctors prescribe the right drug dose to maximize its effectiveness while minimizing the risk of side effects.

How can we broaden our efforts to find gene variants that impact disease prognosis, response to therapy or risk of adverse side effects? By combining large-scale molecular profiling and data collection with bioinformatics, Roden described ongoing projects in precision medicine aimed at discovering new associations. For example, during the check-in process at Vanderbilt outpatient clinics, patients are now given a consent form for a program called BioVU. If they choose to participate, their DNA will be extracted from any blood left over from routine blood tests that would have otherwise been discarded. The DNA is then stored in a de-identified database that can be accessed by researchers. In a related project, called eMERGE, DNA repositories like BioVU are linked with curated clinical data from the patients’ electronic health records, providing a platform for bioinformaticians to mine through the data and uncover new links among specific gene variants, diseases and therapy outcomes.

As an M.D.-Ph.D. student interested in translational medicine, I was particularly curious about tools that could guide clinicians to make better-informed medical decisions based on research findings in precision medicine. One tool is to build guidelines directly into the electronic health record, as Vanderbilt has already done for the drug clopidogrel. In 2010, the FDA added a warning to clopidogrel, a medicine used to prevent blood clots, stating that individual genetic variation alters the efficacy of the drug. Patients who have decreased activity of another liver enzyme due to variants in the CYP2C19 gene are “poor metabolizers” who cannot effectively transform clopidogrel into its active form. Alternative drugs are recommended for patients who are poor metabolizers.

By actively displaying this drug-genome interaction in the patient’s electronic health record, Vanderbilt saw dramatic changes in clinical decision-making related to clopidogrel use. Twelve months into the project, fewer poor metabolizer patients remained on clopidogrel, compared to extensive metabolizer patients (42 percent versus 92 percent), whereas intermediate metabolizers were right in the middle, at 67 percent. Unlike procainamide, clopidogrel is a widely prescribed drug that is used daily by millions of Americans.

The combination of precision medicine and the electronic health record promises to open exciting new possibilities not only to better understand the relationship between genetics and disease, but also to better treat the patient as an individual.

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surgeon focusing

Compassion in Eight Stitches

The first time, you don’t realize how warm his body will be. On some level, you knew the patient’s temperature would be in the range of 98.6 degrees Fahrenheit; his skin, just a few degrees below that. But somehow that information never registered with your fingertips. As you feel the tissue around his wound, palpating for the invisible lines of tension pulling apart its edges, your fingers surprise you. They register warmth, movement, life. Your mind, racing ahead to selection of the suture material, appropriate knot technique and needle placement, is quietly reminded: This man is alive. This man is a person. And you are about to sew his skin like torn denim.

As a second-year medical student, I’ve spent years using suture techniques to repair my ripped jeans and frayed sleeves. I’ve practiced mattress sutures using orange peels and placed subcutaneous stitches into pigs’ feet, but I am only now beginning to close patients’ wounds in the hospital. It’s a very different experience when the target of your needle can feel and think and tell you how much he loves Tom Hanks movies.

On one hand, I remain awed by the unique humanity of my patient: He has a family, a favorite film, dreams and aspirations for the future. On the other hand, to help him, I must concentrate on the biomechanics of the 6 square inches of skin and the curved steel needle immediately in front of me. I continue to be challenged by these discordant principles: How do physicians balance caring for each patient as an individual while maintaining the intense, narrow focus required to perform at the highest level?

To best care for the patient, physicians and medical students need to care about the patient. We treat a person, not a disease. We put ourselves in her shoes, see the world through his fear and pain. This intimate understanding shapes every element of the medical relationship and drives physicians’ compulsion to deliver the best possible treatment.

Embracing the patient’s humanity at the wrong time, however, can cripple a doctor’s ability to help. Consider a neurosurgeon tasked with removing a tumor from a man’s spinal cord:

Doctor, dissect the tumor away from the fasciculus cuneatus. 

This statement is a clear, technical description of the operation’s objective. Now consider the same procedure communicated differently:

Doctor, cut the cancer away from the neurons that let Jim feel the warmth of his daughter’s hand.

carson-patient-pull-quote_102016Can the physician begin to operate with that thought echoing through his or her mind? Compassion mobilizes our hearts, but it can also paralyze our hands. It may sound callous, but during the operation, walling off the part of the brain that sees the patient as Jim, a father, can allow the surgeon to focus on the complex challenge of separating cancer from healthy spinal cord. By temporarily reducing the patient to his anatomy, physicians can incise, inject, staple and stitch with precision and a steady hand.

Is the answer this simple? Are we as medical students expected to care deeply for our patients at all times until a sharp instrument is needed and then promptly disconnect our brains from our hearts? I don’t think so. Humanity is not a light switch to be turned on and off at will. Compassion seeps through whatever mental barriers we construct, imbuing every movement of the instruments with the respect and kindness we feel for the person before us.

You feel the warmth of your patient’s skin and know you will not sew him up like denim. He is not made of fabric. He is made of tissue — delicate, vulnerable and the anatomical building block of this Baltimore man who is looking forward to watching Apollo 13 with his wife this weekend. You begin to sew.

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nurse holds a patient's hand

Cancer Drug Shows Surprising Potential as Parkinson’s Treatment

Parkinson’s disease is a neurodegenerative condition caused by the death of dopamine-producing cells in a region of the brain called the substantia nigra, which leads to disruptions in neural circuits controlling motor function. Although the cause of this inappropriate cell death is largely unclear, one hypothesis is that it is due to the abnormal aggregation of a protein called α-synuclein in damaged neurons. Support for this theory has come from autopsies of patients showing large clumps of α-synuclein in the diseased tissue, but how or why these clumps contribute to Parkinson’s has remained largely unclear.

In a study published in the September issue of Science, researchers from the Institute for Cell Engineering at Johns Hopkins have identified a previously unrecognized role for a protein called lymphocyte-activation gene 3 (LAG3) , which may have critical implications for understanding how α-synuclein is connected to the pathogenesis of Parkinson’s disease. LAG3 is a protein better known for its role in the immune system, where its expression on the surface of immune cells prevents cytotoxic CD8+ T cells from functioning properly in a state of chronic infection or cancer.  Antibodies against LAG3 are being tested as potential cancer treatments, with the hope that by blocking the immune checkpoint receptor protein’s immunosuppressive effects, the patient’s immune system can have a chance to reactivate and more efficiently kill cancer cells.

In neurons, LAG3 plays a much different role, and instead recognizes and interacts with certain materials outside the cell, resulting in their uptake and import. In searching for an answer as to how α-synuclein enters neurons, the researchers found that not only was LAG3 able to import the pathological protein aggregates, but it was also necessary to transport them between cells. They followed up by deleting the LAG3 gene in mice and found that when they injected them with α-synuclein, they developed symptoms of Parkinson’s much more slowly than control mice.

This research is a critical step toward understanding the underlying causes of Parkinson’s disease, since until now, the role of abnormal α-synuclein spread was mostly based on observation and theory, with little mechanistic detail. Now, with the discovery of the role of LAG3, a new door in Parkinson’s research has been opened — with the exciting possibility that a drug already in the pipeline for cancer treatment could potentially benefit the nearly 10 million Parkinson’s disease patients worldwide as well.

Sources

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  2. Mao X, Ou MT, Karuppagounder SS, Kam TI, et al. Pathological alpha-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science. 2016 Sep 30; 353(6307).
  3. Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3 – potential mechanisms of action. Nat Rev Immunol. 2015 Jan; 15(1): 45-56.
  4. ClinicalTrials.gov
  5. Braak H, Sandmann-Keil D, Gai W, Braak E. Extensive axonal Lewy neurites in Parkinson’s disease: a novel pathological feature revealed by alpha-synuclein immunocytochemistry. Neurosci Lett. 1999 Apr 9; 265(1): 67-9.
  6. Statistics on Parkinson’s. Parkinson’s Disease Foundation. 2016.

Read More »Cancer Drug Shows Surprising Potential as Parkinson’s Treatment