Uterus Transplants From Deceased Donors

The first baby has been born following a uterus transplant from a deceased donor according to a recent case study from Brazil. The woman that received the uterus transplant has Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and was born without a uterus.

The transplant surgery took place in September 2016 and lasted 10.5 hours. During the surgery the uterus was connected to the patient's veins, arteries, ligaments, and vaginal canal. Her following treatment consisted of immunosuppressant drugs, antimicrobials, anti-blood clotting medication, and aspirin. Fertilized eggs, which had been cryopreserved, were implanted seven months after surgery and a healthy baby girl was born this year.

This surgery was hugely successful and the patient's fertilized eggs were implanted very quickly compared to past uterus transplant surgeries that often required a year after surgery before implantation. This is the first successful birth following a uterus transplant from a deceased donor despite 10 previous attempts.

Infertility is a widespread issue that affects 10-15% of couples of reproductive age. Uterus transplants are currently only available to women through family members that volunteer as donors. This exciting research could greatly benefit women with uterine infertility and reduce the surgical risk involved in uterus transplants. Using uterus transplants from deceased donors also enables more women to have this option by increasing the potential donor population.

Resources:
Dani Ejzenberg, Wellington Andraus, Luana Regina Baratelli Carelli Mendes, Liliana Ducatti, Alice Song, Ryan Tanigawa, Vinicius Rocha-Santos, Rubens Macedo Arantes, José Maria Soares, Paulo Cesar Serafini, Luciana Bertocco de Paiva Haddad, Rossana Pulcinelli Francisco, Luiz Augusto Carneiro D'Albuquerque, Edmund Chada Baracat. Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility. The Lancet, 2018; DOI: 10.1016/S0140-6736(18)31766-5

The Lancet. (2018, December 4). First baby born via uterus transplant from a deceased donor. ScienceDaily. Retrieved December 5, 2018 from www.sciencedaily.com/releases/2018/12/181204183703.htm

So You Want to be a Doctor: A Complex Hypothetical Case Study

As we have emphasized throughout our coursework this semester, the ethical world of medicine is rarely entirely black and white, and if you aspire to be a healthcare professional, it is a virtual certainty that you are going to be faced with these difficult ethical decisions throughout your career. As a preparation for this, it is helpful to be presented with hypothetical scenarios in an attempt to rationally determine the most ethical course of action. Here I will present one such (very) complicated ethical scenario regarding transgender healthcare.

Before I dive into the scenario itself, some background knowledge and physiology are required. Transgender individuals suffer from what is known as gender dysphoria, a conflict between the individual's physical or assigned gender and the gender with which he/she/they identify (Unger, 2016). This dysphoria can lead to severe depression and suicidal ideations, and the suicide attempt rate of transgender individuals is as high as 32-50%, a staggering number (Virupaksha, 2016). For some physiology background, transgender men often undergo hormone replacement therapy through the administration of testosterone. One known side effect of testosterone is erythropoiesis, or the production of red blood cells (Coviello, 2007). This production results in an increased hematocrit level when measured in the laboratory, as there are literally more red blood cells in circulation. If the hematocrit gets too high, this can obviously be a problem, as you can imagine that too many cells will literally make the blood "thick" and blood flow will be restricted as a result. This can cause a myriad of problems if left untreated, so this level is often monitored for patients undergoing hormone replacement therapy with testosterone.

With all of this background, finally the hypothetical scenario: A transgender man with severe gender dysphoria enters your clinic for a follow up appointment with you. He has been on ongoing testosterone therapy and his latest labs reveal that his testosterone and hematocrit levels are above the desired normal range. You explain the results to the patient and at this point he admits to you that he has been using more than the prescribed dose of testosterone. You strongly counsel him against this and state that you wish to lower his testosterone dose to bring the levels back down to the desired range, but he becomes very upset at this point. He states that if he lowers his dose, he will suffer extreme dysphoria which has caused suicidal ideations in the past. He admits to you that he has previously experienced suicidal ideations and feels that there is no way that he can lower the dose and insists that he has tried before. As his provider, you know that increased testosterone and hematocrit levels carry significant health risks, but the severe gender dysphoria carries risks of its own such as severe depression and possibly suicide. From an ethical standpoint and weighing the beneficence, non-maleficence, autonomy, and justice, what do you do as this patient's provider?

References

Unger, Cecile. (2016). Hormone therapy for transgender patients. Translational andrology and urology, 5(6), 877-884.

Virupaksha, H. G., Muralidhar, D., & Ramakrishna, J. (2016). Suicide and Suicidal Behavior among Transgender Persons. Indian journal of psychological medicine, 38(6), 505-509.

Coviello, A. D., Kaplan, B., Lakshman, K. M., Chen, T., Singh, A. B., & Bhasin, S. (2007). Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. The Journal of clinical endocrinology and metabolism, 93(3), 914-9.

Can Behavior Impact the Severity of Tics?

Tourette's Syndrome is a developmental neuropsychiatric disorder characterized by multiple, recurrent, usually brief, nonrhythmic motor movements and at least one vocalization (motor and phonic tics, respectively) that have onset before age 18, and persist for at least one year.

A study that examines Tourette's syndrome, shows us how a disease can affect people differently based on the area they are living in. In Freeman’s article, “An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries,” Freeman looked into 3,500 individuals in 22 different countries and compared them to each other. The researchers found that the patients with comorbidities were far more likely to express anger control issues than those with none. In looking at patients suffering from comorbidities, the researchers found that the most common was attention deficit hyperactivity disorder to be correlated with Tourette's. Freeman explains “Because behavioral problems are associated with comorbidity, their presence should dictate a high index of suspicion of the latter, whose treatment may be at least as important as tic reduction” (Freeman 2000). Behavior is a major factor that plays into the severity of a patient's tics.

This study is explained as an entry point for larger samples to be studied, but its findings support that with the addition of anger issues and other comorbidities, the problem of tics are far more likely to occur and progress. It is important for future studies to continue to try to understand how mental health issues can play a part in a subjects Tourette’s getting worse. It is also important for future studies to examine the comorbidities in respect to many diseases.

Freeman RD1, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P. An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol. 2000.

Should we start consuming cottonseed oil?

For quite a while now olive oil (OO) has been championed as the healthy alternative to animal based fats, such as butter. Researchers have identified the fact that OO tends to be rich in monounsaturated fatty acids as the primary cause for its healthy characteristics. As most of you in 618 have heard many times by now, these unsaturated fats pose less of a health risk due to their molecular structure and therefore the ease with which they are cleared from the blood (yes, this is a grossly oversimplified explanation). These monounsaturated fatty acids have also been repeatedly linked to reductions of chronic disease factors, especially when replaced for saturated fatty acids and carbohydrates (Schwingshackl & Hoffman, 2014). However, recent research has suggested that other oils with greater concentrations of polyunsaturated fatty acids may be even healthier for individuals (likely due to the same molecular and biochemical reasons). Multiple studies utilizing a variety of different vegetable based oils have been able to demonstrate this, including corn oil (Maki et al., 2014). As of 2018 though, OO, corn oil, and the like are old news and I know that all of you dying to find out the latest nutrition craze. Well, research just published in September has provided evidence to support the idea that cottonseed oil (CSO) may be the latest and greatest vegetable oil. Following a 5-day, high-fat diet rich in CSO, all participating individuals demonstrated a drop in cholesterol, low-density lipoprotein cholesterol, and triglyceride blood levels. In comparison, blood lipid levels were unchanged in the OO control group (Polley, Oswell, Pegg, & Paton, 2018). Given that this was the first study to compare CSO with OO it will be interesting to see if these effects are maintained over time. Unfortunately, nutrition based studies are often extremely difficult to control, due to the vast number of potentially confounding factors at play, and we may therefore never know the true long term effects of CSO compared with OO.

Maki, K. C., Lawless, A. L., Kelley, K. M., Kaden, V. N., Geiger, C. J., & Dicklin, M. R. (2015). Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: results from a randomized controlled feeding trial. Journal of clinical lipidology, 9(1), 49-57.

Polley, K. R., Oswell, N. J., Pegg, R. B., Paton, C. M., & Cooper, J. A. (2018). A 5-day high-fat diet rich in cottonseed oil improves cholesterol profiles and triglycerides compared to olive oil in healthy men. Nutrition Research, 60, 43-53.

Schwingshackl, L., & Hoffmann, G. (2014). Monounsaturated fatty acids, olive oil and health status: a systematic review and meta-analysis of cohort studies. Lipids in health and disease, 13(1), 154.

Mannose sugar to combat cancer cells

Cancer is a very severe disease that has caused many complications and death to individuals all across the world. According to Medical News Today, cancer is the number 2 cause of death in the United States. Due to its complexity, high mutation rate, and rapid growth it has been difficult to treat or even find a cure for cancer. It also has been found that some cancer cells rely heavily on glucose for cell growth. Base on this information, scientist have been researching on a method to starve cancer cells of glucose, however, the challenges is that healthy cells require glucose to function as well.

A new research was conducted by adding mannose sugar into the drinking water of cancer mice and found that tumor cell growth were halted. Mannose sugar is normally taken up by glucose transporter into the cell and becomes mannose-6-phosphate. This impairs the metabolism of glucose through glycolysis, as well as other pathway involved in metabolism. Since mannose essentially is not required for healthy cells to survive and normally can be synthesize through glucose, these scientist predicted that mannose sugar can be used to treat cancer. They decided to administered chemotherapy in combination with mannose sugar and found that it affected anti-apoptotic proteins, which resulted in tumor cells sensitivity to cell death.

This is definitely a breakthrough on how we treat cancer. Hopefully, we can one day develop an effective method to combat all types of cancer and decrease the rate of human death.

https://www.medicalnewstoday.com/articles/282929.php

https://www.medicalnewstoday.com/articles/323786.php

https://www.sciencedaily.com/releases/2018/01/180126095312.htm

https://www.nature.com/articles/s41586-018-0729-3

What the TV drama,'This is Us' can teach you about IVF treatment in obese women

Over break, I was watching an episode of, “This is Us” and in this episode, Kate and her partner, Toby, were going to the doctor's office for a consultation for in vitro fertilization (IVF). Kate was struggling to get pregnant again and despite many treatments and losing a bunch of weight, nothing seemed to be working. Oh, and I forgot to mention: Kate and Toby are obese, and Kate has polycystic ovary syndrome (PCOS), a condition in which the ovaries produce higher than normal levels of androgens thereby causing a widespread effect on a woman’s body, most notably, fertility. Additionally, Toby is on antidepressants which the doctor mentioned could be causing a reduction in sperm count. Due to the high failure rate and risks associated with PCOS and obesity, the doctor initially declines to take Kate on as a patient. The doctor eventually has a change in heart and is willing to take Kate on as a patient so long as she understands the risks involved, including a 90% failure rate in women her size. Desperate to get pregnant, Kate chooses to look at the 10% and agrees to the risks of the procedure

A physician’s ability to refuse to provide IVF treatment in obese women is rather controversial as some physicians are advocating against a BMI cut-off for this treatment. However, evidence has shown that obese women have decreased fertility treatment sucess and are at a greater risk for complications such as from being put under anesthesia for egg retrieval. Additionally, obese women tend to require a greater number of gonadotrophins which are administered in IVF treatment to help stimulate ovulation which raises their risk of developing ovarian hyperstimulation syndrome. Advocates for IVF treatment on obese women argue that the risk is actually small and that patients should receive proper education about the risks and allow the patient to make their own decision. Furthermore, they argue that although livebirth rates in obese women is reduced by 30%, this is still a better success rate than livebirths in older women who are allowed access to IVF (Tremellen, Wilkinson, & Savulescu, 2017) The possibility of a successful pregnancy, even if it’s only 10%, may be enough reassurance for a woman that is desperate to get pregnant and patients should understand their risks and be allowed to make an informed decision about their right to become a parent.

Tremellen, K., Wilkinson, D., & Savulescu, J. (2017). Should obese womens access to assisted fertility treatment be limited? A scientific and ethical analysis. Australian and New Zealand Journal of Obstetrics and Gynaecology,57(5), 569-574. doi:10.1111/ajo.12600

You Won't Find Black Friday Deals at the Hospital

Unlike going to get a haircut or a massage, you never really know how much you are going to be charged for services that are provided to you at a hospital. Sick or injured, visits to the ER are costly, even more so to the uninsured, and rates vary significantly between hospitals. For example, the Federal Centers for Medicare and Medicaid revealed that the same treatment at one hospital in New York cost $100,000, and at a hospital 30 miles away in the same metropolitan city cost $7,000 (Young & Kirkham, 2013). But who has time to comparison shop when your dying?

            Hospitals have what is called the chargemaster, or list of billable services and items to a patient or their health insurance provider. Unfortunately, the chargemaster rates have become hugely inflated, and hospitals can charge patients whatever they want. Hospital lobbyists spend more than the defense and oil industries combined to keep things this way (Brill, 2013). As these inflation rates continue to rise, the price of a single stitch can top $500 (Rosenthal, 2018). In addition, patients receiving treatment from an out-of-network hospital most times will receive adjusted cost-to-charge ratios. Hospitals see these patients as cash cows and charge them significantly more than in-network patients (Bai & Anderson, 2016). These high rates are potentially keeping patients from seeking necessary or life-threatening care, especially the uninsured. In my opinion, policies should be implemented to offer transparency in charges and to protect patients from these high charges. What actions do you think should be taken?

Bai, G., & Anderson, G. F. (2016). US Hospitals Are Still Using Chargemaster Markups To Maximize Revenues. Health Affairs, 35(9), 1658–1664. https://doi.org/10.1377/hlthaff.2016.0093

Brill, S. (2013, March 4). Bitter Pill: Why Medical Bills Are Killing Us. Time. Retrieved from http://content.time.com/time/subscriber/article/0,33009,2136864-1,00.html

Rosenthal, E. (2018, October 19). As Hospital Prices Soar, a Stitch Tops $500. The New York Times. Retrieved from https://www.nytimes.com/2013/12/03/health/as-hospital-costs-soar-single-stitch-tops-500.html

Young, J., & Kirkham, C. (2013, May 8). Hospital Prices No Longer Secret As New Data Reveals Bewildering System, Staggering Cost Differences. Huffington Post. Retrieved from https://www.huffingtonpost.com/2013/05/08/hospital-prices-cost-differences_n_3232678.html

Impact of Stress on Acne

With the approach of finals everyone’s stress levels are increasing. With this stress comes the negative impact that this prolonged stress can have. It is common to believe that stress increases the severity of acne. Many people, including myself, seem to notice an increase in the severity of their acne as stress increases. However, in the research world, support for this phenomenon is not very strong or concrete. Based on what we have talked about in class this semester, it makes sense that an increase in stress could lead to an increase in acne. When we are stressed our parasympathetic nervous system, or rest and digest response, is turned off. It makes sense that prevention of acne, by keeping the pores clear, would be a function of the parasympathetic nervous system. When we have increased sympathetic nervous system action and decreased parasympathetic nervous system action for a prolonged period of time, it is logical that acne will increase.

Bondade, Hosthota, and Basavaraju’s paper explores stress’s impact on acne and somewhat supports this idea (2018). Their results claim that stressful life events do appear to increase the severity of acne flares, but they do not cause new cases of acne to appear. In addition, increases in the release of hormones such as corticotropin-releasing hormone and glucocorticoids have been seen to decrease skin permeability, prevent skin lipid synthesis, decrease antimicrobial defense, and delay wound healing. All of these together could lead to increased acne and slowed healing of acne. Despite these findings, it is generally believed that the impact of stress on acne is not totally clear from a research standpoint. (Bondade, Hosthota, & Basavaraju, 2018) Though stress is widely believed to have an impact on acne, we will not be able to say for sure what the impact of stress on acne is until research with more mathematically significant results are obtained. Nevertheless, based on current available research, we can add this to the ever-growing list of reasons why decreasing chronic stress is important.

Resource:

Bondade, S., Hosthota, A., & Basavaraju, V. (2018). Stressful life events and psychiatric comorbidity

in acne-a case control study. Asia-Pacific Psychiatry: Official Journal Of The Pacific Rim College Of Psychiatrists, e12340. https://doi-org.dml.regis.edu/10.1111/appy.12340

The Physiology of Starvation

It is important to understand that the body will regulate metabolism differently depending on the macromolecules stores that are available. Important changes in metabolism occur in both skeletal muscle and the brain when the body is starving or fasting for a couple of days, compared to when this occurs for a couple weeks.

During the 1-2 day mark, the skeletal muscle will switch from glucose consumption to free fatty acid and ketone metabolism, while the brain will still try and use glucose whenever possible. The liver is also a major player during this phase, because it can activate the Cori cycle to store lactate from glucose and create a lactate reserve that can go through gluconeogenesis to form glucose once again for immediate energy needs (Sherwood, Parris, & Cahill, 1970). During this period of lower glucose levels, insulin levels are also decreased because of less of a need to put glucose into the cells. This will stimulate lipolysis and proteolysis and breakdown triglycerides and proteins. Although the skeletal muscle will use a variety of macromolecules during this initial starvation phase, the brain will continue to use glucose as its primary energy source.

As starvation continues into a week and then to two weeks the rate of proteolysis declines, and the skeletal muscle and brain begin to change their metabolism pattern. If starvation continues long enough the body will begin proteolysis once again but cannot sustain this for long before death. During this phase, the brain will switch from using glucose to using primarily ketone bodies as a source of fuel. At the same point protein breakdown is no longer as efficient because the brain is not in immediate need of glucose made by gluconeogenesis from amino acids.

The use of ketone bodies by the brain is a useful adaptation; however it is important to note that prolonged use of ketone bodies can cause ketoacidosis if the mechanisms to reduce this are not working. The kidney is a prime location where H+ ions can be excreted by converting an ammonia to an ammonium ion and thereby protect the pH balance in the body. Thus the body has useful methods for surviving through starvation, but like any organism there is a limit to how long survival is possible.

Ferrier, D. R. (2014). Biochemistry. Philadelphia: Wolters Kluwer Health/Lippincott Williams &                Wilkins.

Sherwood, L. M., Parris, E. E., & Cahill, G. F. (1970). Starvation in Man. New England Journal of Medicine, 282(12), 668–675. https://doi.org/10.1056/NEJM197003192821209

America’s Next Epidemic

While the American public has remained largely focused on the nation’s biggest drug crisis, the opioid epidemic, another pharmaceutical is quickly making strides towards that title. Benzodiazepines (BZDs) are a class of sedative medications used to treat anxiety and panic, seizures, alcohol withdrawal, and muscle tension. They increase the effects of an inhibitory neurotransmitter called GABA by allosterically binding to the GABA receptor, a ligand gated chloride channel, thereby causing an influx of chloride into the cell. This influx causes a membrane hyperpolarization, which makes it more difficult for subsequent action potentials to occur. Thus, you achieve the inhibitory/anxiolytic effects seen with benzodiazepines (Sankar, 2012).

Although BZDs are quite efficient, there is a growing body of research linking long term benzodiazepine use to cognitive impairments and dementia (Toombs et al., 2018). Similar to opioids, those taking BZDs are subject to increased dependence and withdrawal. Moreover, BZDs can cause fatal overdose when taken in abundance or in combination with other drugs. From 1996-2014, the rate of fatal overdoses involving benzodiazepines quadrupled (Bacchuber et al., 2016).

With this knowledge, why do we continue to prescribe them? The answer is easy, right? Just don’t do it. I would argue that it’s not always that easy. A study of 35 general practitioners investigated reasons why general practitioners decided to initiate benzodiazepine prescriptions. The study concluded that general practitioners tend to become overwhelmed by their patients’ psychosocial problems and perceive benzodiazepines as “the lesser evil” (Anthierens et al., 2007). One general practitioner stated, “I have to do a lot of “psycho”. Whether I want it or not but I haven't got the training for it. What do I do? I prescribe.…”.

From the outside looking in, it’s easy to make judgements, blaming this rising “epidemic” on physicians’ disregard of nonmaleficence. But consider what you would do in a similar situation—when a distressed patient is looking to you for answers. In the case of the practitioner just mentioned, this was likely an attempt to uphold beneficence, by giving a patient the relief he or she needed. Although there is evidence that BZDs are safe in short term, history shows us (i.e. our old pal the opioid crisis) that tapering/refusing to prescribe addictive medications is not particularly easy, especially when there is currently no better alternative. These are the difficult situations that we as future health providers will face.

References:

Anthierens, S., Habraken, H., Petrovic, M., & Christiaens, T. (2007). The lesser evil? Initiating a benzodiazepine prescription in general practice: A qualitative study on GPs’ perspectives. Scandinavian Journal of Primary Health Care, 25(4), 214–219. http://doi.org/10.1080/02813430701726335

Bachhuber, M. A., Hennessy, S., Cunningham, C. O., & Starrels, J. L. (2016). Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013. American Journal of Public Health, 106(4), 686–688. http://doi.org/10.2105/AJPH.2016.303061

Sankar, R. (2012). GABAAreceptor physiology and its relationship to the mechanism of action of the 1,5-Benzodiazepine clobazam. CNS Drugs. https://doi.org/10.2165/11599020-000000000-00000

Toombs, A. R., Jung, J. Y., & White, N. D. (2018). Benzodiazepine Use and Cognition in the Elderly. American Journal of Lifestyle Medicine, 12(4), 295–297. https://doi.org/10.1177/1559827618767381

Our future immigrant colleagues

As future healthcare providers, our ethics discussions in class have largely focused on the patient population we will one day be serving. Recently, we had a discussion regarding immigration (remember the medical school candidate who made a mean comment about immigrants on her Facebook?) Although it is important to reflect on this, what about our future colleagues? Do you really think medical schools are only filled with US born students? I came across an article this afternoon, regarding the prevalence of immigrant healthcare workers. According to a research letter published in JAMA this month pertaining to a census surveying 164,000 US health professionals, 16.6% are immigrants and 4.6% are not US citizens. Professions included in the study ranged from dentists to pharmacists to home health aides to physicians. When it’s broken down, this accounts for nearly a third of physicians being born outside of the US and a quarter of dentists. Additionally, 18% of biomedical research run in the US is run by immigrant graduates. Those are a lot of numbers and percentages but hopefully, the point is clear: our healthcare system does not only serve a population of immigrants, it is also run by one. Part of the reason is because these individuals are willing to work in underserved communities, places where US-born medical school graduates often rather not serve. Do we often think about the prejudice the other way around? Would our medical school candidate have made the same comment about a physician? I have prediction about that, do you?

References:

Patel, Y. M., Ly, D. P., Hicks, T., & Jena, A. B. (2018). Proportion of Non–US-Born and Noncitizen Health Care Professionals in the United States in 2016. JAMA, 320(21), 2265–2267. https://doi.org/10.1001/jama.2018.14270

https://www.pbs.org/newshour/health/new-study-shows-1-in-6-u-s-health-care-workers-are-immigrants