Myelodysplastic syndromes (MDS) can be a confusing diagnosis. Dr. William Pearse, one of our newest hematologists, taught our residents about this group of disorders.
MDS refers to a heterogeneous group of hematopoietic stem cell disorders that are characterized by bone marrow dysplasia, ineffective hematopoiesis, and a variable risk of transformation to acute myeloid leukemia (AML). This is typically triggered by somatic mutations, though familial MDS also exists. Patients with MDS present with peripheral cytopenias (most commonly anemia) and may range from being completely asymptomatic to having debilitating symptoms. After ruling out reversible causes of these abnormalities, such as nutritional deficiencies, a bone marrow biopsy is required to make this diagnosis.
Cytogenetic (chromosomal) abnormalities hold diagnostic, prognostic, and therapeutic implications. For example, MDS with isolated del(5q) is generally very responsive to oral lenalidomide (a board favorite). Certain translocations and inversion are diagnostic of AML. Except for select cases, molecular profiling (i.e., analysis of individual genes) is not currently used for diagnostic purposes but will become important in the near future.
Treatment of MDS depends on the patient’s symptoms, degree to cytopenias, subtype of MDS, and risk of transformation to AML (as assessed by the Revised International Prognostic Scoring System, IPSS-R), among other factors. Since hematopoietic stem cell transplantation (HSCT) is the only potentially curative therapy and is not appropriate for most patients, the goal of MDS treatment is to improve quality of life. Options, therefore, include observation, supportive care, oral medications, chemotherapy, and HSCT.
Thank you, Dr. Pearse, for a fabulous talk! We would also like to thank Dr. Kendal Flegenheimer, one of our RACE Track residents, for helping organize the session.
This morning our future chief resident and professorial R3, Alex Tong, presented a case of a young woman with recurring fever. He then elicited a broad differential from the residents on possible causes of recurring fevers by dividing it into the categories of: Infectious, Rheum, Malignant, and Misc. With the help of our expert discussant, Dr. Paul Hsu, residents walked through the differential to further clarified the HPI and physical exam. Together they reviewed what labs to order and based on patients clinical picture and lab abnormalities, highest on the differential was Adult Still’s Disease.
We had a fabulous lineup for today’s General Internal Medicine Friday School!
Osteopathic Manipulative Medicine (OMM)
Dr. Alice Chen, Assistant Professor of Family Medicine and Public Health and Director of UCSD Health’s inpatient OMM consult service, taught our residents about OMM. The philosophy behind osteopathic medicine is that we are an integrated unit of body, mind, and spirit and that our bodies possess naturally self-healing physiologic mechanisms. The osteopathic structural exam focuses on tissue texture changes, asymmetry, range of motion, and temperature changes and uses these signs of somatic dysfunction to direct treatment. Dr. Chen shared examples of how OMM approaches musculoskeletal dysfunction, impaired lymphatic flow, and somatic and visceral pain. Reasons to consult OMM include pain, acute infections, gastrointestinal distress, postprocedural or postsurgical pain, and recurrent admissions for the same issue.
We then transitioned to a phenomenal talk on toxic alcohols by Dr. Bryan Corbett. Ethanol is ultimately metabolized to carbon dioxide and water through the citric acid cycle and does not produce an acidosis per se. The hallmark of a toxic alcohol is one that is metabolized to a carboxylic acid metabolite and leads to an anion gap metabolic acidosis. Compounds that do this include methanol and ethylene glycol, forming formic acid and oxalic acid, respectively. (Unlike these two compounds, isopropyl alcohol is metabolized to acetone rather than a carboxylic acid and does not cause acidosis!)
Earlier on, before the toxic alcohol is metabolized, you may not see an anion gap. Instead, you will see a osmolar gap (i.e., measured osmolality – calculated osmolality, with normal being -10 to +10). As a reminder, you can calculate the serum osmolality using the formula: Calculated osmolality = 2 [Na] + [glucose]/18 + [BUN]/2.8 + [ethanol]/4.1. (These laboratory studies must be drawn at the same time to be interpretable!) As the alcohol is metabolized, the anion gap increase, although the presence of ethanol may delay this process since alcohol dehydrogenase will preferentially metabolize ethanol. Also, keep in mind that the absence of an osmolar gap does NOT rule out toxic alcohol ingestions, especially with toxic alcohols with lower molecular masses (e.g., methanol).
Important toxic alcohols to consider include:
Methanol (wood alcohol): Methanol is found in windshield washer fluid, illicit distillation, and many solvents. Its metabolite, formate, inhibits oxidative phosphorylation and leads to lactic acidosis. Methanol is also directly toxic to retina (“snowfield” blindness) and to basal ganglia (e.g., putaminal necrosis). Of note, folate increases formate metabolism to carbon dioxide and water.
Ethylene glycol: Ethylene glycol is found in antifreeze. It is metabolized to oxalate and produces calcium oxalate stones, which can lead to renal failure and hypocalcemia. Urine fluorescence (added to most antifreeze) and falsely high point-of-care lactate levels (from the intermediate metabolic glycolic acid) can be seen. Thiamine and pyridoxine increase breakdown to nontoxic metabolites.
Propylene glycol: Propylene glycol in “safer” antifreezes and is in fact used as a diluent in many medications (e.g., lorazepam)! It is metabolized to lactate, which we have endogenous processes (i.e., Cori cycle) for metabolizing. However, long-term, high-dose infusion can still lead to lactic acidosis!
Isopropyl alcohol, found in rubbing alcohol, does not cause acidosis but will produce an osmolar gap. It is also quite intoxicating and can cause hemorrhagic gastritis.
Now that you’ve diagnosed the intoxication, how do you treat it? The goal is to block metabolism of the toxic alcohol, using ethanol (target level: 100 mg/dL) or fomepizole (15 mg/kg loading dose, followed by 10 mg/kg Q12H for 48 hours and 15 mg/kg Q12H thereafter – EXPENSIVE!). Hemodialysis may be required to remove the toxic alcohol/metabolites and/or to reverse the acidosis, especially in cases of renal failure.
RACE4ALL: Growth Mindset
Switching gears, we moved onto a session on Growth Mindset led by our very own Dr. Connie Chace. She taught us the difference between a fixed mindset and a growth mindset. A person with a fixed mindset often sees failure as a sign of permanent deficiency. This is associated with poorer learning and achievement outcomes. Unfortunately, the medical profession predisposes us to a fixed mindset.
However, we can shift our mindset! A person with a growth mindset instead focuses on the process of learning, is curious about challenges ahead, sees failures as opportunities, and appreciates feedback. We can foster a growth mindset both in ourselves and in others by praising wisely, rebranding and normalizing failure, using deliberate language with the word “yet,” giving process-focused feedback, and modeling a growth mindset yourself! The same techniques are also effective for encouraging a growth mindset in our educators (e.g., fellows, attendings, mentors). A growth mindset is infectious!
Our residents had an opportunity to do some role-playing and practice these skills.
We wrapped up the day with continuity clinic reorientation. A huge thank-you to all of our speakers and continuity clinic attendings for another successful Friday school!
This morning our inquisitive R2, Eddy Wang, presented a case of an elderly gentleman who presented with progressive dyspnea and cough. We reviewed his chest x-ray which showed a large pleural effusion that pushed the trachea left. With the help of our expert discussant, Dr. Peralta, we reviewed chest x-ray findings of pneumonia vs atelectasis vs effusion vs pneumonectomy; particularly what can happen to the trachea. The patient then underwent thoracentesis and our we reviewed what labs to order for the fluid, particularly given the CT abnormalities noted on the periphery of the pleura. Then a rapid response was called on our patient at and a repeat chest x-ray showed a new opacity. Eddy then reviewed the typical presentation and management of re-expansion pulmonary edema. Our patient’s labs returned and our patient was diagnosed with mesothelioma. Our residents then reviewed what military exposures are associated with lung cancer given our patient’s service history.
This morning our wonderful junior resident, Tally Desmarais, presented a case as part of her RACE Track pathway. She shared the initial presentation of an elderly female who presented with subacute, progressive shortness of breath and weakness. The patient was found to be hypotensive, anemic, and volume overloaded with acute renal failure. Our residents then got into groups to discuss initial management of this presentation. Then with the help of our brilliant expert discussant, Dr. Antoinette Birs, Tally reviewed the images of our patient’s echocardiogram which showed findings concerning for cardiac tamponade. They then reviewed physical exam findings, pathophysiology, as well as the common causes of cardiac tamponade.
Take Home Points:
Common causes: neoplastic, postviral, uremic, and hemorrhagic
Physical exam findings: “beck’s triad” of JVD, hypotension, and muffled heart sounds. Also look out for pulsus paradoxus, sinus tachycardia, and signs of right heart failure.
Echo findings: pericardial effusion, right sided chamber collapse, plethoric IVC
Today our stellar R2, Mehul Trivedi, gave a RACE Track case presentation of an elderly woman who presented with fatigue, DOE, and tachycardia. On initial labs our patient had a new anemia! With the help of our expert discussant, Dr. Gupal, he reviewed the initial work up for the new anemia and determining the etiology. As the work up results came in, our residents were concerned for a hemolytic anemia. Mehul then explained how a Direct Coombs Test works and we found that our patient had warm autoimmune hemolytic anemia! He then discussed primary vs secondary as well as treatment.
Take Home Points:
LDH, Indirect Bilirubin, Haptoglobin, Reticulocytosis are all markers of hemolysis
Blood smears can be helpful in ruling out MAHA/TTP, also in showing spherocytes
Positive Coombs test is diagnostic for warm autoimmune hemolytic anemia
Treatment depends on whether it is primary vs secondary and consists of transfusion for acute cases, and steroids/rituximab chronically
Tonight, we were joined by all of the UCSD IM pathway directors, pathway CMRs, and current pathway residents for a Pathway Open House! Thank you to everyone who joined! Don’t worry if you weren’t able to make it tonight, all the info you need is on the blog. Also, feel free to reach out to the pathway directors and chief residents at any time!
We will be sending all the residents more information about how to apply this coming Winter soon!
Hospital Medicine Pathway
Pathway Director: Dr. Ali Farkhondehpour
CMR: Ashley Scanlon
Primary Care Pathway
Pathway Director: Dr. Stacy Charat
CMR: Lauren Haggerty
Pathway Directors: Dr. EB Sladek & Dr. Samantha Spilman
CMR: Armando Martinez
Pathway Directors: Dr. Supraja Thota and Dr. Connie Chace
CMR: Averie Tigges & Lizzy Hastie
Global Health Pathway
Pathway Director: Dr. Annie Cowell
CMR: Lizzy Hastie
The pathway powerpoints and a recording of the presentations can be accessed here:
Today was our first day of the Rheumatology Friday School Block and part of our Resident As Clinician Educator for All (RACE 4 All) curriculum!
From 1-3pm, RACE Track Director, Dr. Supraja Thota shared tips on how to be an amazing team leader and teach on rounds. She included a mini-workshop on the “holdover game,” helping residents to make holdovers into a rich, interactive cognitive reasoning exercise that can help avoid anchoring!
From 3-5pm, residents and interns gathered in small groups to come up with creative questions to test their co-residents on the clinical manifestations, work up and treatment of SLE! Dr Maripat Corr from our Rheumatology Department then reviewed SLE with us! With her help, and the help of our new resident experts in SLE, we were able to answer all the fun (but difficult) questions made by each small group! While we were able to cover a lot, learning about SLE is not restricted to Friday School! Check out this amazing article on SLE for the internist in the Annals of Internal Medicine! Click Here!
Today one of our amazing RACE track residents, Dr. Eric Low, discussed a fascinating case of an elderly woman who presented with altered mental status and was found to have a profound metabolic acidosis secondary to metformin overdose! Dr. Low used this case as the impetus for an excellent discussion on the general approach to acid/base disorders as well as ensuring our ability to identify the rare triple acid/base disorder! Thank you to our expert discussant Dr. Warda Zaman for her helpful pearls as well!
Take Home Points:
Remember the difference between emia (the state of being) and osis (the process).
Develop a system for approaching acid/base disturbances (try Eric’s!).
Make sure to work through acid/base disturbances completely to rule-out concomitant disorders.
An elevated anion gap is never normal and always implies an underlying acidosis (make sure to correct for albumin!).
Today, RACE track superstar Masha Barsky presented a fascinating case of a patient in their 40s with newly diagnosed HIV/AIDS (CD4 27, VL 126K) who had 2 weeks of dry cough and progressive shortness of breath. We went through a great diagnostic schema of approaching respiratory disease in an HIV/AIDS patient, including both HIV/AIDS-specific diagnoses and diagnoses pertinent to immunocompetent and immunocompromised patients. The patient underwent a multitude of tests which revealed a positive AFB sputum and MTB-PCR, as well as chest imaging concerning for miliary TB! We then reviewed miliary TB, including distinctions between pulmonary vs miliary (disseminated) TB and additional work-up needed to evaluate for extrapulmonary involvement. Thank you to our expert discussant, Dr. Jocelyn Keehner, for her insights!
Use a diagnostic schema for an HIV patient with respiratory symptoms that includes bacterial/fungal/parasitic/viral infectious causes as well as several non-infectious causes – consider HIV/AIDS-specific diagnoses and the CD4 counts associated with them, but don’t forget diagnoses that can occur in anyone as well!
Evaluate carefully for extra-pulmonary involvement in miliary TB, including dedicated imaging for any suspected organ abnormality and a lumbar puncture for any neurologic symptoms.
Pulmonary TB can occur in HIV/AIDS patients with any CD4 count, while miliary TB is more likely to occur in HIV/AIDS patients with CD4 count <100-200.