Today our amazing future chief Dr. Averie Tigges discussed a case of a young man with SCI admitted for UTI, but used the case to discuss the greater concept of malnutrition. Averie walked us through some of the prior rationale for using pre-albumin and then discussed why it is actually not a useful bio-marker for malnutrition (its a negative acute phase reactant!) . She then discussed the different clinical scores available to assess malnutrition and highlighted the choosing wisely recommendation to utilize one of these scores over pre-albumin for assessment of malnutrition.
This afternoon, Kimberly Kreitinger presented the case of a female in her 50s with a history of metastatic colorectal cancer. The patient has had a course involving treatment for the past 4 years with FOLFOX + Avastin, which was stopped due to HTN, FOLFOX + cetuximab, SBRT to lung and liver lesions, then targeted therapy with trastuzumab and pertuzumab, though demonstrated disease progression. The patient was then considered for immune checkpoint inhibitor therapy with Pembrolizumab, a PD-1 inhibitor.
We discussed the tested indications for the use of ICIs in the treatment of metastatic colorectal cancer. Notably, multiple trials have demonstrated efficacy in prolonging progression free survival and improving overall survival in patients with metastatic CRC, but in patients demonstrated to have either mismatch repair deficiency (MMR-D) or high degrees of microsatellite instability (MSI-H). These trials demonstrated the effectiveness of Pembrolizumab (PD-1 inhibitor), Ipilimumab (a CTLA-4 inhibitor), or the combination of Ipilimumab and nivolumab (PD-1 inhibitor). The rationale behind the use of ICIs in these patients is that those with defective MMR are felt to be prone to indels or frameshift mutations, which may confer increased immunogenicity due to epitope formation.
The patient was found on genomic testing to have microsatellite stability, though demonstrated intermediate levels of tumor mutational burden (TMB) and high levels of Tumor infiltrating lymphocytes (TILs), which may have favorable prognostic profiles with regard to response rates to ICI therapy–active research performed by investigators here at UCSD! Much of this data is preliminary, though provides us with a glimpse of advanced therapies for patients whose disease has progressed beyond standard systemic chemotherapeutic options. Thank you to Dr. Sacco for her expert input and Kim Kreitinger for a great case presentation.
This afternoon, we discussed two topics outlined by the Journal of Hospital Medicine’s Choosing Wisely topic series: 1. Routine TSH testing in hospitalized patients, and 2. Card Flipping on Hospital Medicine Ward Rounds.
Card Flipping on Rounds, otherwise known as “table rounding,” involves the discussion of patient care plans away from the bedside. Some of the reasons for why this is done include perceptions of efficiency, desires to shield ward teams’ discussions regarding sensitive patient subjects (malignancy or patient behaviors), or desires that certain teaching topics are more appropriate at the table rather than the bedside. However, arguments in support of bedside rounding are that bedside rounding may actually improve efficiency due to having nursing staff, ancillary services, the patient, and other members of the care team involved in the decision making conversation, thus eliminating confusing that may occur later in the day. It was also discussed that many patients actually prefer bedside rounding due to improved transparency with regard to care, as well as feelings that they were included in the decision making process. Ultimately, we discussed the need to have a balanced, thoughtful approach when choosing what rounding format is most appropriate for each clinical scenario, as well as addressing the practical time demands that often obligate a mixed use of table rounding and bedside rounding. We discussed that decisions to utilize bedside rounding for its clear benefits in patient engagement, involvement of multidisciplinary teams, and physical exam teaching were superior to that of table rounding– but that table rounding formats could be useful in times when clinical decision making is relatively straightforward (i.e. in the case of placement issues).
The second discussion we had was regarding the routine testing of TSH in hospitalized patients. While it would appear that TSH is tested for “completeness,” in reality the use of TSH in hospitalized patients very rarely leads to a diagnosis of true thyroid disease. In fact, up to 30% of hospitalized patients may have an abnormal TSH when tested during hospitalized settings, only to have true thyroid disease confirmed in subsequent outpatient testing in only 8% of those patients, yielding an incredibly high false-positive rate. We discussed the utilization of Bayes Theorem to highlight this further–as many patients who have routine testing of TSH may have a low pre-test probability of having thyroid dysfunction– using a test with a high false positive rate in that setting nearly completely ameliorates the test specificity. Nevertheless, it was noted that in some clinical scenarios where clinical findings suggestive of thyroid diseases were noted — goiter on physical exam, lethargy, or unexplained tachycardia, the likelihood ratio of underlying thyroid dysfunction was significantly elevated and the use of TSH as a confirmatory test was deemed to be warranted. In essence, developing an awareness of the statistical limitations of tests used in variable risk populations will go far to improve our understanding of diagnostic testing and their utilities in different clinical scenarios.
This afternoon, Sophie Cannon presented an interesting case of a female in her 30s with a history of chronic urticaria who presented in respiratory distress, tachycardia and throat swelling following the ingestion of a meal prepared at a restaurant. A similar event had happened previously, months ago though the symptoms were not as severe, and self resolved. This prompted the discussion of upfront recognition and treatment of patients whose presentations are concerning for anaphylaxis, the diagnosis of which is purely clinical, and can be made in the following scenarios:
We also reviewed the pathophysiology of the various mechanisms by which anaphylaxis occurs. Most are likely familiar with the canonical IGE mediated pathways, Which upon re-exposure, allergen-specific IgE antibodies bind to allergens and form allergen-specific IgE immune complexes, which then activate mast cells and basophils, causing degranulation and release of preformed histamine, leukotriene, prostaglandins, and platelet activating factor. There are several additional pathways worth mentioning, including the non-IgE pathways involving IgG, cytokine release response pathways involving IL-6, IL-1B, and TNFa, mixed CRR/IgE pathways, as well as the direct complement C5a activating pathways.
The patient was ultimately treated with IM Epinephrine, which prompted resolution of the patient’s respiratory symptoms, glucocorticoids to help prevent biphasic anaphylaxis, as well as antihistamines to treat the patient’s pruritis and skin manifestations. Thank you to Sophie and Dr. Broide for a great case, and fantastic teaching!
Take Home Points:
- Anaphylaxis is a clinical diagnosis; early recognition and empiric treatment can prevent respiratory and cardiovascular collapse and death
- Multiple mechanisms lead to “anaphylaxis,” including those that are mediated by T-cells and macrophages, which may present with a sepsis-like presentation, due to release of pro-inflammatory cytokines IL-6, IL-1B, and TNF-a
- IM Epinephrine is the gold standard therapy upfront and is the only measure that has been shown to effectively treat respiratory compromise associated with anaphylaxis. Glucocorticoids, antihistamines, and leukotriene modulators are all adjunct strategies and should not be used in place of epinephrine. Caution should be used when considering IV Bolus epinephrine, as outcomes have not been demonstrated to be superior, but have instead been linked to cardiovascular complications such as MI/Stroke.
Figures were adapted from Wilfox et al, Journal of Asthma and Allergy, 2018
Today at Jacobs, we discussed two common practices in hospital medicine which, current evidence suggests, should be done away with: the use of docusate for prevention and treatment of constipation and assumption of a historical penicillin allergy without further investigation. Our residents digested the “Things We Do For No Reason” articles on these subjects, and then presented the information to each other in quick, 5-minute chalk talks! The “Things We Do For No Reason” series is a quick and easy tool to highlight both high value care, as well as quick, relevant topics to teach about on wards (you only need 20 minutes of prep time!). Check out our residents in action!
This week, Diego Vargas presented the case of a middle aged man who had presented with rectal pain, hematochezia, fevers and chills. He was found to have metastatic rectal adenocarcinoma, complicated by local abscess and fistula formation, and was septic. The patient was stabilized with several courses of broad spectrum antibiotics and referred to our medical center for further evaluation of his cancer. Upon initial work up, CT chest/abdomen/pelvis revealed liver metastases as well as intraabdominal and intrathoracic lymph node involvement. Moreover, the case was complicated with a worsening AKI, findings of hyperuricemia to 11, hyperkalemia, and mild hyperphosphatemia, raising suspicion for potential spontaneous tumor lysis syndrome.
We discussed TLS in more detail and the types of malignancy that are most likely to have TLS as a consequence of treatment–primarily liquid hematologic malignancies were the most likely etiologies (acute leukemias/lymphomas, burkitt’s lymphoma, etc). More rarely, solid tumors can also present with TLS following treatment–these tumor types have been mainly described in case reports–breast cancer, SCLC, and widely metastatic colon cancer. Spontaneous TLS is not commonly seen in solid tumors.
We also discussed the Cairo-Bishop criteria for Tumor Lysis Syndrome, which include both laboratory and Clinical criteria as a tool to help establish TLS in the right clinical setting. It is important to note that these criteria apply primarily for cases either <3 days or >7 days following treatment, which may be chemotherapy or radiation.
Ultimately, the it was felt that while the patient’s tumor had metastasized the ultimate tumor burden and the fact that it was a solid tumor was an unlikely cause of the patient’s multiple electrolyte abnormalities and renal dysfunction, but rather it was more likely that an AKI was the causative etiology to explain the former. Thank you Diego for a great, live case and we appreciate Dr. Husain’s expert input!
- Hematologic malignancies are much more likely to cause tumor lysis syndrome following initiation of chemotherapy. Solid tumors, unless with aggressive SCLC, breast cancer or metastatic colon ca, are much less likely to have TLS as a consequence of treatment.
- Spontaneous tumor lysis can occur in tumors with very high cell turnover–most commonly aggressive acute leukemias and lymphomas.
- The Cairo-Bishop criteria may help with the identification and recognition of TLS if clinical suspicion is high.
Today at Jacobs, we continued with our hematology conference series by discussing a case of an elderly patient with high risk MDS who presented with neutropenic fever! With the assistance of expert hematologist Dr. Choi, we had an excellent discussion about the most pertinent features of MDS. See the slideshow below for some of the highlights of our discussion!
Today at Jacobs, we continued with our hematology conference series by discussing a case of a young woman presenting with acute neurologic changes, MAHA, and thrombocytopenia! We discussed the delineation between MAHA (a descriptive term) and TMA (the pathologic process), the initial work-up, and a schema to approach TMA in general. Dr. Erin Reid, our expert hematologist, provided an amazing discussion on TMA and refined our residents’ approach to diagnosing some of the potentially life-threatening causes of TMA! Ultimately, she was diagnosed with pregnancy-associated TTP and improved with plasmapheresis!
Today at Jacobs, we worked on some RACE track concepts through a hospital medicine lens! The residents paired up to discuss 2 articles from SHM’s Choosing Wisely campaign, “Things We Do For No Reason.” They then prepared a 5 minute chalk talk based on the articles to present to our small group! The teams learned just how easy it can be to quickly synthesize some high yield topics into a deliverable for wards!
This afternoon at Jacobs, we continued to explore our longitudinal clinical reasoning curriculum by doing a deep dive into the concept of the diagnostic schema! As a reminder, the diagnostic schema is a conceptual approach to specific symptoms or diseases that is meant to organize the way we approach a differential diagnosis. Importantly, the schema does not need to be entirely comprehensive, but is built such that you can rationally approach a disease category and use it to guide work-up and management. As an example, the team discussed their different approaches to post-prandial pain!