Monthly Archives: January 2024

Biology

Cell type evolution reconstruction across species through cell phylogenies of single-cell RNA sequencing data – Nature.com

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Cell type evolution reconstruction across species through cell phylogenies of single-cell RNA sequencing data - Nature.com

Biology

Glycoscience Explained: The Sugar Coating of Life – SciTechDaily

Glycobiology, evolving beyond its roots in carbohydrate chemistry, is now a key field in understanding lifes molecular mechanisms. Glycans, essential in various biological functions, are the focus of groundbreaking research and technological innovations, revealing their critical roles in health and disease. Credit: SciTechDaily.com

Researchers are working to advance the field of glycoscience, illuminating the essential role of carbohydrates for human health and disease.

In the narrowest sense, glycobiology is the study of the structure, biology, and evolution of glycans, the carbohydrates and sugar-coated molecules found in every living organism. As a recent symposium at MIT made clear, the field is in the midst of a renaissance that could reshape scientists understanding of the building blocks of life.

Originally coined in the 1980s to describe the merging of traditional research in carbohydrate chemistry and biochemistry, glycobiology has come to encompass a much broader and multidisciplinary set of ideas. Glycoscience may actually be a more appropriate name for the rapidly growing field, reflecting its broad application not just to biology and chemistry but also to bioengineering, medicine, materials science, and more.

Its becoming increasingly clear that these glycans have a very important role to play in health and disease, says Laura Kiessling, the Novartis Professor of Chemistry. It may seem daunting initially, but devising new tools and identifying new kinds of interactions requires exactly the sort of creative problem-solving skills that people have at MIT.

Glycans include a diverse set of molecules with linear and branched structures that are critical for basic biological functions. With no known exception, all cells in nature are coated with these sugar molecules from the intricate chains of sugars surrounding most cellular surfaces to the conjugated molecules formed when sugars attach like scaffolding to lipids and proteins. Theyre absolutely fundamental to life. For example, Kiessling points out that the most abundant organic molecule on the planet is the carbohydrate cellulose.

Sperm-egg binding is mediated by an interaction between a protein and a carbohydrate, she says. None of us would exist without these interactions.

Though talking about carbs and sugars might leave some people focused on their diet, glycans are actually among the most important biomolecules out there. They store energy and, in some cases like cellulose, provide the structural framework for multicellular organisms. They mediate communication between cells; influence interactions like that between a host and parasite; and shape immune responses, disease progression, development, and physiology.

In Professor Laura Kiesslings lab, researchers are working to understand the protein-carbohydrate interactions at a molecular level, such as the protein human intelectin-1 (hiTLN-1) shown here. Understanding the proteins glycobiology could facilitate the development of new antibiotics and antimicrobial therapeutics. Credit: Kiessling Lab

It turns out that some of these structures, which we didnt even know existed in the body in such abundance until recently, have so many different biological functions, says Andrew and Erna Viterbi Professor of Biological Engineering Katharina Ribbeck. With this rapid expansion of knowledge, it feels like were just beginning to understand how diverse and important those functions are to biology.

With a better understanding of how ubiquitous and critical these molecules are, researchers in applied fields like biotechnology and medicine have turned their attention to glycoscience as a tool to pinpoint the drivers of disease.

Many conditions have been linked to defects in how glycans are produced in the body or issues with glycosylation, the process by which carbohydrates attach to proteins and other molecules. That includes certain forms of cancer. Cancer cells have even been shown to cloak themselves in certain glycoproteins to evade an immune response.

On the flip side, glycans may be a repository of potential therapeutics. The blood thinner Heparin, one of the worlds best-selling prescription drugs, for example, is a carbohydrate-based drug.

Glycans and sugar-binding proteins like lectins even help influence the exchange of microbes across mucus layers in the human body, from the brain to the gut. Glycans dangling off mucus interact with microbes, letting good ones in and reducing the virulence of problematic ones by interrupting cell signaling or stopping pathogens from releasing toxins.

Despite how crucial this sugar coat is, for a long time, molecular biologists focused on nucleic acids and proteins, paying relatively little attention to the sugars that coated them.

The tools we have to examine the functions of other molecules are largely absent for glycans, says Kiessling, who is also an institute member of the Broad Institute of MIT and Harvard.

For example, the DNA and RNA sequences of a cell predict what proteins that cell makes, so scientists can track where a protein is and what its doing using a genetically-encoded tag. But the structure of glycans isnt so obviously encoded in a cells DNA, and a single protein can be decorated with many different chains of carbohydrates.

In addition, the immense diversity of forms carbohydrates can take, and the fact that they break down quickly in the bloodstream, has made it challenging to synthesize glycans or target them for drug development. So, creative new methods are needed to track them.

Its a classic chicken-and-egg situation. As scientists better understand the importance of glycans for so many biological processes, it has incentivized them to develop better tools for studying glycans, in turn, producing even more data on just what these molecules can do. In 2022, in fact, the Nobel Prize was awarded to Carolyn Bertozzi at Stanford University, a pioneer in glycobiology, for her work on tracking molecules in cells, which she and others have applied to glycans.

But artificial intelligence could facilitate an evolutionary leap in the field.

I think glycobiology is, more than almost any other field, ripe and ready for an AI interpretation, Ribbeck says, explaining how AI might enable scientists to read the glycan code in the same way they have with the human genome. That would allow researchers to predict the actual function of a glycan based on data about its structure. From there, they could identify what changes lead to disease or increase disease susceptibility and, most importantly, come up with ways to repair those defects.

The increasing interest in computation reflects the inherent interdisciplinarity that has defined glycoscience from the beginning.

Just at MIT, for example, related research is happening across the Institute. Kiessling describes MIT as a playground for interdisciplinary research, which has enabled significant advances in the field with applications to biotechnology, cancer research, brain science, immunology, and more.

In the Department of Chemistry, Kiessling is studying carbohydrate-binding proteins, and how their interactions with glycans affect the immune system. Shes also working with Bryan Bryson, an associate professor in the Department of Biological Engineering, and Deborah Hung, a core faculty member at The Broad Institute of MIT and Harvard, using carbohydrate analogs to test differences in strains of tuberculosis in South Africa. Meanwhile, assistant professor of biological engineering Jessica Stark is pioneering approaches to better understand the roles of glycans in the immune system. Tobi Oni, a fellow at the Whitehead Institute for Biomedical Research, is looking to glycans to help detect and target tumors in pancreatic cancer. Barbara Imperiali, the Class of 1922 Professor of Biology and Chemistry, is studying the carbohydrates that envelop the cells of microbes like bacteria, and Professor Matthew Shoulders in the Department of Chemistry is studying the role of glycans in synthesizing and folding proteins.

Were at a very exciting and unique position combining disciplines to address and answer entirely new questions relevant for disease and health, says Ribbeck.The field in and of itself is not new, but what is new is the contribution that MIT, in particular, could make with a creative combination of science, engineering, and computation.

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Glycoscience Explained: The Sugar Coating of Life - SciTechDaily

Pediatrics

Recurrent Syncope Unveiling Pulmonary Hypertension Secondary to Pulmonary Artery Thrombi in a Pediatric Patient – Cureus

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Recurrent Syncope Unveiling Pulmonary Hypertension Secondary to Pulmonary Artery Thrombi in a Pediatric Patient - Cureus

Pediatrics

ChatGPT bombs test on diagnosing kids’ medical cases with 83% error rate – Ars Technica

Enlarge / Dr. Greg House has a better rate of accurately diagnosing patients than ChatGPT.

ChatGPT is still no House, MD.

While the chatty AI bot has previously underwhelmed with its attempts to diagnose challenging medical caseswith an accuracy rate of 39 percent in an analysis last yeara study out this week in JAMA Pediatrics suggests the fourth version of the large language model is especially bad with kids. It had an accuracy rate of just 17 percent when diagnosing pediatric medical cases.

The low success rate suggests human pediatricians won't be out of jobs any time soon, in case that was a concern. As the authors put it: "[T]his study underscores the invaluable role that clinical experience holds." But it also identifies the critical weaknesses that led to ChatGPT's high error rate and ways to transform it into a useful tool in clinical care. With so much interest and experimentation with AI chatbots, many pediatricians and other doctors see their integration into clinical care as inevitable.

The medical field has generally been an early adopter of AI-powered technologies, resulting in some notable failures, such as creating algorithmic racial bias, as well as successes, such as automating administrative tasks and helping to interpret chest scans and retinal images. There's also lot in between. But AI's potential for problem-solving has raised considerable interest in developing it into a helpful tool for complex diagnosticsno eccentric, prickly, pill-popping medical genius required.

In the new study conducted by researchers at Cohen Childrens Medical Center in New York, ChatGPT-4 showed it isn't ready for pediatric diagnoses yet. Compared to general cases, pediatric ones require more consideration of the patient's age, the researchers note. And as any parent knows, diagnosing conditions in infants and small children is especially hard when they can't pinpoint or articulate all the symptoms they're experiencing.

For the study, the researchers put the chatbot up against 100 pediatric case challenges published in JAMA Pediatrics and NEJM between 2013 and 2023. These are medical cases published as challenges or quizzes. Physicians reading along are invited to try to come up with the correct diagnosis of a complex or unusual case based on the information that attending doctors had at the time. Sometimes, the publications also explain how attending doctors got to the correct diagnosis.

For ChatGPT's test, the researchers pasted the relevant text of the medical cases into the prompt, and then two qualified physician-researchers scored the AI-generated answers as correct, incorrect, or "did not fully capture the diagnosis." In the latter case, ChatGPT came up with a clinically related condition that was too broad or unspecific to be considered the correct diagnosis. For instance, ChatGPT diagnosed one child's case as caused by a branchial cleft cysta lump in the neck or below the collarbonewhen the correct diagnosis was Branchio-oto-renal syndrome, a genetic condition that causes the abnormal development of tissue in the neck, and malformations in the ears and kidneys. One of the signs of the condition is the formation of branchial cleft cysts.

Overall, ChatGPT got the right answer in just 17 of the 100 cases. It was plainly wrong in 72 cases, and did not fully capture the diagnosis of the remaining 11 cases. Among the 83 wrong diagnoses, 47 (57 percent) were in the same organ system.

Among the failures, researchers noted that ChatGPT appeared to struggle with spotting known relationships between conditions that an experienced physician would hopefully pick up on. For example, it didn't make the connection between autism and scurvy (Vitamin C deficiency) in one medical case. Neuropsychiatric conditions, such as autism, can lead to restricted diets, and that in turn can lead to vitamin deficiencies. As such, neuropsychiatric conditions are notable risk factors for the development of vitamin deficiencies in kids living in high-income countries, and clinicians should be on the lookout for them. ChatGPT, meanwhile, came up with the diagnosis of a rare autoimmune condition.

Though the chatbot struggled in this test, the researchers suggest it could improve by being specifically and selectively trained on accurate and trustworthy medical literaturenot stuff on the Internet, which can include inaccurate information and misinformation. They also suggest chatbots could improve with more real-time access to medical data, allowing the models to refine their accuracy, described as "tuning."

"This presents an opportunity for researchers to investigate if specific medical data training and tuning can improve the diagnostic accuracy of LLM-based chatbots," the authors conclude.

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ChatGPT bombs test on diagnosing kids' medical cases with 83% error rate - Ars Technica

Pediatrics

ChatGPT is terrible at diagnosing child medical cases, according to new study – Mashable

OpenAI's ChatGPT is no closer to replacing your family physicians, as the increasingly advanced chatbot failed to accurately diagnose the vast majority of hypothetical pediatric cases.

The findings were part of a new study published in JAMA Pediatrics on Jan. 2, conducted by researchers from Cohen Children's Medical Center in New York. The researchers analyzed the bot's responses to requests for medical diagnosis of child illnesses and found that the bot had an 83 percent error rate across tests.

The study used what are known as pediatric case challenges, or medical cases originally posted to groups of physicians as learning opportunities (or diagnostic challenges) involving unusual or limited information. Researchers sampled 100 challenges published on JAMA Pediatrics and NEJM between the years 2013 and 2023.

ChatGPT provided incorrect diagnoses for 72 out of 100 of the experimental cases provided, and generated 11 answers that were deemed "clinically related" to the correct diagnosis but considered too broad to be correct.

The researchers attribute part of this failure to the generative AI's inability to recognize relationships between certain conditions and external or preexisting circumstances, often used to help diagnose patients in a clinical setting. For example, ChatGPT did not connect "neuropsychiatric conditions" (such as autism) to commonly seen cases of vitamin deficiency and other restrictive-diet-based conditions.

The study concludes that ChatGPT needs continued training and involvement of medical professionals that feeds the AI not with an internet-generated well of information, which can often cycle in misinformation, but on vetted medical literature and expertise.

AI-based chatbots relying on Large Language Models (LLMs) have been previously studied for their efficacy in diagnosing medical cases and in accomplishing the daily tasks of physicians. Last year, researchers tested generative AI's ability to pass the three-part United States Medical Licensing Exam It passed.

But while it's still highly criticized for its training limits and potential to exacerbate medical bias, many medical groups, including the American Medical Association, don't view the advancement of AI in the field just as a threat of replacement. Instead, better trained AI's are considered ripe for their administrative and communicative potential, like generating patient-side text, explaining diagnoses in common terms, or in generating instructions. Clinical uses, like diagnostics, remain a controversial, and hard to research, topic.

To that extent, the new report represents the first analysis of a chatbot's diagnostic potential in a purely pediatric setting acknowledging the specialized medical training undertaken by medical professionals. Its current limitations show that even the most advanced chatbot on the public market can't yet compete with the full range of human expertise.

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ChatGPT is terrible at diagnosing child medical cases, according to new study - Mashable

Pediatrics

Missouri pediatricians provide eight parenting goals to start the new year strong – Kirksville Daily Express and Daily News

Missouri Chapter, American Academy of Pediatrics

New Year resolutions are often sweeping and grand, but sometimes you can reap the biggest rewards by building off the strengths already in place. Helping to make your family safer, stronger and more harmonious in 2024 may not require a complete overhaul, but rather a few strategic tweaks.

There is no time like the new year to plan how you are going to practice health and wellness as a family, said Dr. Maya Moody, President of the Missouri Chapter, American Academy of Pediatrics (MOAAP). Families are already doing great things, but there are always ways to make the time you spend with your loved ones even better.

Here are eight goals for parents and caregivers:

Get everyone up to date on recommended immunizations. Vaccines are the best way to protect yourself, your children, and other loved ones from dangerous viruses such as flu and covid, which are spiking among children. Call your pediatrician to make sure your children are up to date on all recommended immunizations, and ask any questions you may have. And remind your children that good hand hygiene habits help prevent the spread of germs.

Do good digital. What are your kids watching on TV and online? Devote some time to researching age-appropriate media. Make a family media use plan and try to prevent gaming from becoming an unhealthy habit. Remember that screen time shouldn't always be done solo. Watch a show together and discuss whats happening. Play a video game together. Screen time can become bonding time when adults are active participants.

Read together. Set aside time for reading each day. For younger children, build it into the bedtime routine. For older children and teens, share a favorite book by taking turns reading aloud or listen to audiobooks together. Reading has so many brain-boosting benefits for kids. Reading together also strengthens that special bond between you and your child.

Get outside and explore. Spending time outdoors can be a great mood booster, and help families get needed physical activity and vitamin D while enjoying time in nature. Spending time outside also give your child's eyes a healthy screen-time break and help them sleep better at night.

Check your car seat limits for safety. Kids grow so fast and they can easily outgrow car seats faster than parents realize. Keep children riding rear-facing as long as possible, up to the limits of their car seat, because it is the safest mode. This commonly includes children under 2 and most children up to age 4. See if there are any new car seat laws that may be going into effect in your state in the new year. Remind anyone who transports your child by car to abide by all safety rules.

Set aside time to cook as a family. Many families enjoy baking treats together during the holidays. Keep the fun going in the new year. Schedule special times to cook together and get children involved, from choosing recipes to buying ingredients at the store. If your child is a fussy eater, this can get them more interested in trying new, healthy foods.

Make a family disaster kit. It's scary to think how disasters like wildfires, hurricanes or tornados could affect our communities, but extreme weather events are becoming more frequent due to climate change. Being ready is one way to be less afraid. Ask your children what they would want with them in a disaster and assemble necessities, like non-perishable foods, flashlights, and bottled water, for when a disaster strikes.

Mind your mental health and practice self-care. When was the last time you had a check-up? Got proper rest? Depression and anxiety can happen to both moms and dads during and after pregnancy, even up to three years after having a child. The National Maternal Mental Health Hotline is available 24/7 by calling 1-833-943-5746. And for non-emergency resources and support, you can contact Postpartum Support International: call or text "Help" to 1-800-944-4773.

Additional useful tips:

Healthy New Year's Resolutions for Children & Teens

Making Physical Activity a Way of Life

Healthy Self-Care for Teens: 4 Ways Families Can Help

About MOAAP

The Missouri Chapter, American Academy of Pediatrics (MOAAP) represents more than 1,100 physicians, trainees, and pediatric-provider members throughout Missouri. Our mission is to promote the health of all Missouris children through advocacy, education, and collaboration. For more information, visit missouriaap.org.

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Missouri pediatricians provide eight parenting goals to start the new year strong - Kirksville Daily Express and Daily News

Pediatrics

The clinical takeaways of the RSV immunizations – Contemporary Pediatrics

Welcome to the final episode of our 5-episode series; respiratory syncytial virus (RSV) Roundtable, a collaborative project fromContemporary Pediatrics,Contagion, andContemporary OB/GYN.

This series discusses several aspects of RSV including incidence rates, vaccines, and immunizations.

In this episode, our panel offers their insights on the implications that the RSV immunizations may have now and in the future.

Our panel of clinicians includes:

Click here for all episodes of this RSV Roundtable video series.

Thank you for watching RSV Roundtable.

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The clinical takeaways of the RSV immunizations - Contemporary Pediatrics

Pediatrics

Reviewing the 2023 RSV season and an outlook on 2024 – Contemporary Pediatrics

In this video interview, Tina Tan, MD, FAAP, FIDSA, FPIDS, editor in chief, Contemporary Pediatrics, professor of pediatrics, Feinberg School of Medicine, Northwestern University, pediatric infectious diseases attending, Ann & Robert H. Lurie Children's Hospital of Chicago, recaps 2023 with regard to respiratory syncytial virus (RSV).

Tan breaks down the severity of the RSV season in 2023, how newly FDA approved preventive tools have changed the treatment landscape, and what could be in store for 2024.

Interview transcript (edited for clarity):

Contemporary Pediatrics:

Hello and thanks for watching. I'm Joshua Fitch, editor of Contemporary Pediatrics. Today I'm joined by Dr. Tina Tan, editor in chief of Contemporary Pediatrics and a pediatric infectious disease attending at Ann and Robert H. Lurie Children's Hospital in Chicago. Dr. Tan, thank you for being here. First, let's talk about what a year it's been when it comes to RSV. Going back to about a year ago, when it was a very difficult RSV season, can you take us back and recap that a little bit, and really the urgent need for some some new treatment for this obviously, very young population?

Tina Tan, MD, FAAP, FIDSA, FPIDS:

Yeah, absolutely. So RSV causes annual epidemics, but last year, what we were noticing is that there wasn't just 1 epidemic, but there were actually several surges of RSV that occurred out of its normal season. So RSV normally occurs between October and March here in the United States and for reasons that are still not understood, we actually had several surges last year with 1 surge actually occurring during the summer. But it was the fall surge, which started earlier, that really was incredible, because we also were having surges of influenza, as well as COVIDa nd what that ended up doing was it overwhelmed the pediatric health care system so that there really were few to no hospital beds that were available at any given time. There were children that actually had to be transported either by ambulance or helicopter to other states in order to be treated and hospitalized for complications that they were having from RSV. It really did point out the fact that we did not have any way of preventing RSV disease, and that we really needed to have other tools in order to decrease the amount of severe RSV that we were seeing that was placing kids and infants in the hospital.

Contemporary Pediatrics:

Thank you Dr. Tan, of course, like you just mentioned, that harsh of an RSV season then turned into those new tools and vaccines to prevent the disease, including nirsevimab approved in July 2023 and Pfizer's maternal vaccine approved in August. Obviously, this was an exciting time looking back, can you kind of discuss what these approvals meant at that time, and really still mean now for RSV disease?

Tan:

That was fantastic news, because it really put other tools in our toolbox that we could use to prevent the severe complications that were being seen with RSV, especially in the younger infants under 6 months of age. And not only were we able to give a monoclonal antibody to the infants under 8 months of age, but we also were able to vaccinate pregnant women between 32 and 36 weeks so that they would be able to pass antibody on to their babies during a time when the baby would be at greatest risk for having complications should they get RSV, so it was really fantastic news that we had 2 different tools available that could decrease the amount of severe RSV disease that was being seen.

Contemporary Pediatrics:

To quickly follow up on that, you explained it from the health care professional standpoint. In your day-to-day, talk about kind of a sense of relief, if there was one from the parents standpoint, as they were the ones also dealing with their child having RSV disease, the cause for concern. Can you touch on that, what you've seen and what kind of relief these these approvals have brought?

Tan:

When nirsevimab was first approved, there were parents that were literally calling and clamoring to try and get the vaccines for their babies or the monoclonal antibody for their babies. Talking to some of my ob-gyn colleagues, there were women that were asking for RSV vaccine because they understood, because many of them had other children that this could be a potentially severe infection that their younger baby could get, and so they were actually asking the ob-gyn for the vaccine. So, I think that the word has gotten out that we do have something that can prevent hospitalization and other complications in these very young babies.

Contemporary Pediatrics:

You mentioned the word getting out. Well, recently following the approvals, the next question heading into September and October was availability, mainly with nirsevimab as it turned out. In October, the CDC recommended it'd be prioritized for the highest risk infants, amid some limited availability. Can you talk about some of the rollout challenges you've noticed, and availability now that we're into the RSV season and the winter months?

Tan:

It really has been a challenge for individuals to get an adequate supply of nirsevimab. Nobody has an adequate supply. People are prioritizing their 100 mg doses, which is recommended for infants that are 5 kilos and greater in weight to those infants that are under 6 months of age, infants that have underlying conditions, and infants that are Alaskan Native, American Indian infants, because we know that these are infants that are at the greatest risk for complication, should they get RSV.

Contemporary Pediatrics:

Is that kind of an unprecedented situation to where here's the brand new tool we've been talking about for so long, but now, how do we get it to everyone? Have we seen this before on such a large nationwide scale.

Tan:

We've seen this before, in some of the severe influenza seasons, where individuals were not able to get enough influenza vaccine to vaccinate their patients. So it's not unheard of that this happened and I think what probably occurred is that there was an underestimation of the demand that would happen once the product was released.

Contemporary Pediatrics:

Thank you, Dr. Tan. Lastly, we've kind of reviewed start of 2023 to now, looking ahead in your opinion, where do you think we stand when it comes to these preventative treatments? What trends have you noticed this RSV season, and if you can speak to any national trends as well, that'd be great, as we close out 2023 and really look into 2024's winter months.

Tan:

Right now we are starting to see a surge in RSV in many different areas of the country. It still remains to be seen how effective the limited amount of nirsevimab being given and maternal immunization being uptaken will have in terms of impacting the amount of severe RSV disease that we're seeing. My hope is that there is going to be some impact it might not have been as great as we would have liked to seen, but I would hope that there would be some impact with the use of the nirsevimab available and the maternal vaccination on the amount of severe RSV disease that may occur.

Contemporary Pediatrics:

Dr. Tan thank you so much for speaking with us.

Tan:

My pleasure.

See the article here:

Reviewing the 2023 RSV season and an outlook on 2024 - Contemporary Pediatrics

Internal Medicine

Medical Mystery Case: What Landed This Pregnant Woman in the Hospital? – Medpage Today

Internal medicine and rheumatology specialist Siobhan Deshauer, MD, reviews the case study of a pregnant woman who was hospitalized.

Following is a partial transcript of the video (note that errors are possible):

Deshauer: Hey, guys. I'm Siobhan, an internal medicine and rheumatology specialist. Today, I'm going to tell you about Emma. She is a 31-year-old woman who landed her dream job, first violinist in a prestigious orchestra, and she has never had any health issues until recently.

Emma and her husband have been struggling to get pregnant over the past 2 years and she is now seeing a fertility specialist. Anxious to find a treatment that would work for her, Emma also started seeing another health practitioner who recommended various supplements that she was told were safe and effective. Unfortunately, she has been hiding this from her doctor and little did she know that decision would land her in the hospital and change the next few years of her life.

Over the past few weeks, Emma has had abdominal pain, nausea, and vomiting. She had a glimmer of hope thinking she might be pregnant, but the tests kept coming back negative. Her symptoms just kept getting worse and it was starting to affect her ability to perform at the orchestra. She was sure that her colleagues were starting to notice. After one particularly poor performance, she decided to go to the doctor. Her doctor checked her vitals, ordered some blood work, along with an abdominal ultrasound. Everything looked fine, so her doctor thought it might just be stress from the new job, but the pain and nausea worsened to the point that she was barely able to eat anything.

Finally, after a horrible episode of vomiting, her husband brought her to the emergency department. Her blood work showed mild anemia. Her red blood cells were a bit too low. After her vitals were normal and her imaging was normal, she was sent home with an iron supplement and told to follow up with her family doctor in about 2 weeks.

Over the next few days, her symptoms just continued to progress. She had to call in sick from work and was spending most of the day in bed exhausted and in pain. But Emma didn't want to go back to the hospital, wait for hours, and then just get sent home again. Then one day she was getting out of bed, she became so dizzy that she fell to the ground on her knees. Her husband heard the sound, ran upstairs and found her on the ground. That was it. They were heading back to the hospital.

In the emergency department, her heart rate was a little bit fast, but it was her blood work that was alarming. Emma's hemoglobin was much lower than before, so low that she required a blood transfusion. Emma was actually relieved to hear that they had found something to explain her symptoms, but the question remains why was her hemoglobin dropping so dramatically? The emergency doctor explained that she might be bleeding from her stomach. That would explain her abdominal pain and the drop in her hemoglobin. The plan this time was to admit her to hospital.

A few hours later, a tired-looking internal medicine resident came to assess Emma. When asked about medications, Emma responded that she is taking levothyroxine, a thyroid supplement, and follitropin alfa injections for infertility. When asked about supplements, she only mentioned her prenatal vitamins.

Now, remember Emma is also taking supplements for infertility, but she didn't want to tell the doctor because she was worried about being judged and she couldn't imagine that it was relevant in this situation. Emma's blood tests not only showed that she was anemic with too few red blood cells, but that the cells were too small. We call this microcytic anemia. In situations like this, her bone marrow should be going into overdrive, pumping out as many new red blood cells as possible, but another test called the reticulocyte count proved that this wasn't the case for Emma.

When I see a patient like this with microcytic anemia, a whole bunch of causes come to mind. But by far, the most common cause is iron deficiency, especially in a young woman. Think about iron deficiency like this: either you're not eating enough iron, your body is not absorbing that iron, or you're bleeding and then losing the iron.

Emma's blood work is consistent with iron deficiency with a ferritin level lower than expected. This suggests that she has a low amount of iron stored away in her body and maybe the bone marrow wasn't creating enough red blood cells because it didn't have enough iron available. But iron deficiency itself doesn't cause abdominal pain, so her doctors wondered if she might be bleeding somewhere in her abdomen, maybe a bleeding peptic ulcer.

In the emergency department, Emma already had a CT scan of her abdomen and an ultrasound, both of which were normal. You may be surprised to learn that often a CT scan or an MRI won't actually find the cause of a GI bleed. Often the bleeding is coming from an erosion in the protective layer of the gut and you really need to camera down the GI tract to be able to see that.

The next day she was wheeled down to the endoscopy suite and sedated. First, a camera was inserted into her throat, no signs of bleeding. Then she had a colonoscopy and again totally normal. Okay, so no bleeding in the GI tract where we can see.

Another thing we have to consider in a woman who is having abdominal pain and unexplained anemia is endometriosis, which is a disease where tissue similar to the lining of the uterus grows elsewhere in the body. Just like the uterus does, the tissue thickens up, breaks down and then bleeds with each menstrual cycle. This could be a hidden source of blood loss. It can also cause severe pain, especially in the pelvis, and it can also cause infertility. This could actually tie together all of Emma's symptoms including her recent diagnosis of infertility. Endometriosis is notoriously difficult to diagnose and it can be missed on imaging, which is why surgery is often needed to help make the diagnosis. Emma agreed to go ahead with the exploratory laparoscopy and a few days later she was taken to the operating room.

She was put under general anesthetic and the surgeons got to work. They poked small holes in her abdomen and inserted a small tube with a light and camera attached. They also insert another tube that pumps air into the abdomen. This raises up the abdominal wall so it's possible to look around at the organs and then operate if necessary.

The surgeon carefully examined each of Emma's organs, looking for any signs of endometriosis, which would look something like this. But they only found one abnormality, a simple cyst on her ovary, far from a slam-dunk diagnosis and probably unrelated to her symptoms. But nonetheless, the surgeons took a biopsy of the cyst and sent it off to the pathology lab to be examined. But if it doesn't look like endometriosis, what else could it be?

Emma's medical team went back to the drawing board to rethink her case. She eats a diet containing enough iron. She has no signs of malabsorption and they couldn't find any signs of bleeding, so maybe the blood work showing iron deficiency is just a red herring and there is another cause for her anemia that hasn't been considered. Could this be a production problem, an issue stemming from the bone marrow where the red blood cells are made? Well, there is only one way to find out, going straight to the source.

Emma was prepped for a bone marrow biopsy where a needle is inserted into the bone to take a sample of the semi-solid tissue inside. Making over 500 billion blood cells per day, our bone marrow is constantly working hard to keep us alive. Now, it's a waiting game. The results from the bone marrow won't be back for a few weeks, so Emma was discharged home with a diagnosis, anemia NYD (not yet diagnosed). But on a positive note, her abdominal pain had improved and as she was leaving the hospital she was told to restart her usual home medications and to come back if things got worse. When she got home, she restarted her fertility injections and those fertility supplements again.

Emma was still really tired and soon she developed a new headache and she was never someone to get headaches. Plus, tinnitus, that high-pitched ringing in her ears that just wouldn't go away. She kept track of her symptoms until she had her follow-up appointment 2 weeks later. Hearing about her new neurological symptoms, the internal medicine team decided to expand their diagnostic search to include another rare cause, porphyria.

This is a very rare group of conditions that affects how your body makes heme, an important part of hemoglobin, and some patients experience porphyria attacks, which can include anemia, neurological symptoms, and abdominal pain. It was a stretch and they knew it. But if you never look for those rare causes, you'll never find them, so her doctors ordered a urine test to screen for the disease.

Two weeks later Emma had another follow-up appointment to go through results. She was nervous, but hopeful that she might walk away with some answers this time. First, the surgical biopsy. It was normal, no endometriosis or cancer. Good. Next, the bone marrow results. It showed some increase in iron stores, but it was otherwise normal, so again no diagnosis.

Then a result that finally gave them a lead, Emma's porphyria screening show high levels of copper porphyrin III and delta-ALA. Okay. Now, porphyria screening is a whole can of worms that we don't have time to unpack right now, but the key point is that this particular result really narrows things down to either porphyria or lead poisoning.

Emma was sent back to the lab this time to have her blood lead levels drawn. Two days later, Emma got a phone call from her doctor's office. Her blood lead levels were off the chart. Finally, she has a diagnosis. Emma is suffering with lead poisoning. This explains all of her symptoms: abdominal pain, nausea, and vomiting. These are classic, early signs of lead toxicity.

Neurological symptoms take some time to develop, which explains why her headache and tinnitus came on later. This also explains her anemia. Lead accumulates in the bone marrow, blocking certain enzymes that produce heme, an important part of hemoglobin. Less heme means smaller red blood cells and it also limits the bone marrow's ability to create more cells, ultimately causing hypoproliferative microcytic anemia.

But why did her porphyria testing come back positive? Well, as lead blocks important enzymes that produce heme, that leads to a buildup of byproducts. Think of it like the conveyor belt in the factory that's making heme is broken and as a result there is a buildup of raw materials. Those raw materials are copper porphyrin III and delta-ALA. That's why her porphyrin screening came back positive. It's so cool, right? Everything leads back to lead poisoning. Had her doctors ordered a blood lead level earlier, it would have saved Emma so many needless investigations.

Siobhan Deshauer, MD, is an internal medicine and rheumatology specialist in Toronto. Before medicine, she was a violinist, which is why her YouTube channel is called Violin MD.

The rest is here:

Medical Mystery Case: What Landed This Pregnant Woman in the Hospital? - Medpage Today

Dermatology

FDA Approves Berdazimer Gel, 10.3% for the Treatment of Molluscum Contagiosum – Dermatology Times

The US Food and Drug Administration (FDA) announced today its approval of Ligand Pharmaceuticals Incorporated's berdazimer gel, 10.3% for the treatment of molluscum contagiosum in patients ages 6 months and older.1

This approval makes berdazimer gel only the second FDA-approved treatment for this indication, following the approval of Verrica Pharmaceutical's Ycanth (formerly VP-102) in July of last year.

The approval of [berdazimer gel] Zelsuvmi is a breakthrough, marking the first time that clinicians can treat molluscum with an efficacious topical prescription medication that is applied by the patient, or a family member, said Mark D. Kaufmann, MD, FAAD, clinical professor of Dermatology in the department of dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York and past president of the American Academy of Dermatology, in a press release. I look forward to having this novel medication to treat my molluscum patients.

The approval comes just under a year after the FDA accepted its New Drug Application (NDA) for berdazimer in March of 2023.2

The NDA and approval are based on positive data stemming from the B-SIMPLE4 (NCT04535531) trial, published in the Journal of the American Medical Association Dermatology.3

In the phase 3 study, berdazimer gel demonstrated statistically significant improvements in the clearance of treatable molluscum contagiosum at week 12.

Additionally, berdazimer gel was well-tolerated among patients, with the most common adverse events reported as being mild application site pain and mild-to-moderate erythema.

Key outcomes of the study also included a lesion count of 0 or 1 of all treatable molluscum contagiosum at week 12, a 90% reduction from baseline in the number of all treatable molluscum contagiosum at week 12, complete clearance of all treatable molluscum contagiosum at week 8, and a change from baseline in the number of all treatable molluscum contagiosum at week 4.

The approval of berdazimer gel, 10.3% marks a significant milestone in the treatment of this burdensome, highly contagious condition.

Authors of the B-SIMPLE4 study wrote, "Molluscum contagiosum infection is usually self-limited, yet may persist for months to years, generating a substantial health care burden and quality-of-life concerns necessitating therapeutic intervention.Treatment may also be warranted because of its highly contagious nature and concern for infecting peers or household members.Additionally, outwardly visible lesions may be associated with discomfort and psychosocial stigma, and may scar after resolution.

References

Read more here:

FDA Approves Berdazimer Gel, 10.3% for the Treatment of Molluscum Contagiosum - Dermatology Times