All posts by The Chiefs

Diagnosing plasma cell dyscrasias

Remember this pearl covered in CUH morning report last week regarding the sensitivity of the work-up for myeloma spectrum disorders:

  1. SPEP alone – sensitivity is 82%
  2. SPEP plus immunofixation– sensitivity is 92%
  3. SPEP plus immunofixation plus either Serum free light chains OR UPEP– sensitivity is 98%

At CUH & Parkland, the new SPEP always reflexes to immunofixation, so really what you should remember to do is send either the serum free light chains or the 24-hour UPEP, keeping in mind that SFLC is much easier logistically to do. If patients are admitted anyway, though, in practice, hematologists will recommend obtaining all 3 SPEP / SFLC / 24-hr UPEP.

 

Viral Arthritis

This week at CUH MR, we talked about viral arthritis:

– Viral arthritis – responsible for about 1% of all cases of acute arthritis

– World-wide, parvovirus B19, hep B / C, HIV, and arboviruses (specifically alphaviruses, which includes chikungunya) are the most important causes of virally mediated arthritis

  • Most commonly, viruses will cause a symmetric polyarthritis (similar in distribution to RA); HIV – arthralgias are more common than true arthritis

– Serologic testing may help the diagnosis but also helpful are associated clinical features that point to a specific virus (slapped cheek rash in parvovirus; jaundice related to hepatic injury in hepatitis viruses)

– Treatment goals are relief of symptoms and maintenance of function: acetaminophen / NSAIDs in doses typically used in inflammatory arthropathy like RA; steroids are discouraged because of limited utility in most viral arthritis; there is no role for anti-virals because the illness is self-limited in most cases

R2s Dr Eule and Dr Sumarsono Publish!

 

 

It’s been a big week for our second-year residents as two of them have had first author publications.

Eule Paper

Dr. Corbin Eule had his publication “The Direct Antiglobulin Test for Evaluating Anemia” published in JAMA this week as part of their Diagnostic Test Interpretation series. Dr. Eule presents a patient case and the results of their labs and asks the reader to interpret them in a multiple-choice question. He then provides a nice overview of the DAT test. Co authors on the paper include Dr. Arjun Gupta (former chief resident and current hematology/oncology fellow at Johns Hopkins) and Dr. Srikanth Nagalla (hematology/oncology fellowship program director). Read the paper here.

Sumarsono Paper

Dr. Sumarsono had his publication “A 57 Year-Old Man With Subacute Progressive Hemoptysis and Fevers” published in CHEST. The paper details a case of a man presenting with hemoptysis and found to have an unusual diagnosis that was first considered after a specific physical exam finding. Co-authors on the paper include Dr. Timothy J Brown (current chief resident), Dr. Stan Atkin (former resident, current OHSU hospitalist), and Dr. Jason Clark (intensivist). Read the paper here.

Management of TTP

This week at morning report, we discussed TTP. Here is how you should think about the management of TTP:

Plasma Exchange: cornerstone of treatment. Perform daily until there is a complete response (see below).

Rituximab: beneficial to start early, there is data that suggests better remission rates when added to plasma exchange upfront.

Steroids: adjunctive because there is minimal data to back this up, but generally recommended if there is no contraindication.

These treatment modalities are initiated early and urgently in a patient with presumptive TTP. Treatment is continued until there is a complete response, which is defined by a platelet count above 150,000 for two consecutive days, together with normal or normalizing LDH and clinical recovery (ie end organ damage has resolved). After treatment, patients are most vulnerable to a recurrence within the first week after tapering of therapy. Patients are followed closely to assess for symptoms and for CBC/ADAMTS13 monitoring. What is unclear is what to do with patients who are asymptomatic but have a down trending/low ADAMTS13. In this situation, data suggests that treatment with rituximab can reduce the possibility of relapse, likely through decreasing the production of the antibodies inhibiting ADAMTS13.

 

Who needs HCC screening?

Guidelines differ slightly between the different liver societies (AASLD & EASL & APASL) but most agree that we should screen the following high-risk groups:

  • Patients with Child Pugh A or B cirrhosis
  • Patients with Child Pugh C cirrhosis, only if awaiting liver transplant
  • Non-cirrhotic patients with HBV infection & any of the following characteristics:
    • Active hepatitis (ALT and/or high viral load)
    • Family history of HCC
    • Africans & African Americans (age does not matter)
    • Asian males > 40
    • Asian females > 50
  • +/- Chronic HCV & advanced fibrosis (stage F3), rather than strict cirrhosis

Keep these in mind when you’re seeing your PCIM & PRIME patients!

MEN Syndromes

Last week at the VA, we discussed a case of MEN1 in morning report! Here are some pearls about MEN syndromes:

MEN1: The 3 Ps”

  • Primary hyperparathyroidism – 90%
  • (Anterior) Pituitary tumor – 40%
    • MC prolactinoma à GH + prolactin à GH  à non functioning
    • ACTH / TSH secreting tumors are rare
  • Pancreatic islet cell tumor
    • Gastrinoma (ZES) – 30-40%
    • Insulinoma – 10%
    • Non-functioning – 20-55%

Caused by autosomal dominant mutation in MEN1 tumor suppressor gene

Clinical dx: 2+ MEN1 tumor types OR occurrence of 1 MEN tumor in a family member of a patient with diagnosis of MEN1

Who gets genetic testing? Any index patient with clinical MEN1, 1st degree relative of known MEN1 carrier regardless of symptoms, individuals with “suspicious or atypical MEN1”; if asymptomatic, offer genetic testing first to avoid extensive imaging / lab work-up

Who to screen: index patients & 1st degree relatives.

How to screen: Follow clinically for amenorrhea, galactorrhea, ED, growth abnormalities, nephrolithiasis, cushingoid changes, PUD / diarrhea, hypoglycemia, HA, visual changes. Labwork:  annual Ca, PTH, gastrin (fasting), glucagon, VIP, pancreatic polypeptide, chromogranin A, insulin, fasting glucose, prolactin, IGF-1. Radiology: There is no consensus on radiologic screening guidelines – suggest annual pancreatic imaging with EUS/MRI/CT and MR pituitary q3-5 years

MEN2A & B:

  • caused by autosomal dominant mutation in RET proto-oncogene
  • MEN2A – has 4 variants, 60-90% of MEN2 syndromes
  • MEN2B –  5% of all MEN variants
  • Manifestations:
    • Medullary thyroid carcinoma – typically earliest manifestation & almost all patients with MEN2 have it
    • Pheochromocytoma – 50%
    • Primary hyperparathyroidism – 10-50% of only MEN2A patients
    • cutaneous lesions / mucosal neuromas, Hirschsprung’s disease
  • thyroid, parathyroid, adrenal glands are at risk of developing tumors that reduce life expectancy –> importance of early diagnosis because of the excellent prognosis of medullary thyroid cancer if diagnosed early
  • Who to screen: as a result, you screen first and second degree relatives of an index case.
  • How to screen: plasma metanephrines, calcium / PTH, calcitonin and thyroid / neck US

Infective endocarditis

Today at morning report, we discussed a case of tricuspid valve  endocarditis in IVDU. Here are some points to keep in mind about endocarditis:

Subacute bacterial endocarditis – often due to strep species of low virulence (mainly viridans strep); clinical course is slowly progressive, indolent over weeks to months, has low propensity to embolize

Acute bacterial endocarditis –  fulminant disease over days to weeks, more likely staph aureus, and frequently causes metastatic infection

 

Microbiology: based on a large cohort 2700+ patients with infective endocarditis:

  • ​Staph aureus – 31%
  • Viridans group strep (oral flora) – 17%
  • CoNS – 11%
  • Strep bovis – 7%
  • Other strep – 5%
  • Enterococcus – 11%
  • Then, atypical organisms: HACEK – 2% / Fungi – 2% / non-HACEK gram negative organisms – 2%; 8% are culture-negative
In IVDU, staph aureus is still the most common – especially MRSA – followed by strep species and enterococcus; though we classically think of gram negative endocarditis (pseudomonas, E coli) in association with IVDU, these are rarer.
Indications for surgery: The class I indications (ACC / AHA guidelines) can be categorized as such:
  • ​heart failure – valvular dysfunction causing refractory pulmonary edema or cardiogenic shock
  • Prevention of embolization – vegetation > 10 mm with prior embolization (class I) or isolated vegetation > 15 mm and feasible valve repair (class IIb); recurrent emboli despite appropriate antibiotic therapy (class II)
  • uncontrolled infection – resistant organism – S. aureus (in many cases), fungi (candida, aspergillus) – (class I), persistent cultures after 7-10 days appropriate therapy (class I); enlarging vegetation despite 7-10 days appropriate therapy (class I), other evidence of uncontrolled infection defined as abscess / fistula / pseudoaneurysm (class I)
  • prosthetic valve endocarditis
  • neurologic complications – TIA / ischemic stroke without hemorrhagic conversion, cerebral abscess, silent microembolism
The indications for surgery in endocarditis associated with IVDU are generally the same though in general, surgery is not advised unless the patient agrees to enter drug rehabilitation program post-operatively. In IVDU, there is a risk of co-infection with HIV/Hepatitis B/C, but the presence of HIV infection is not a contraindication though it is considered higher-risk by CT surgery in advanced AIDS. Unfortunately, outcomes after surgery for patients with IE and IVDU are often poor: though they have similar short-term mortality, they have a substantially higher long-term mortality (noted at 60% in 13 months in 1 study; 45% at 20 months in another study) though these outcomes are related to risk of reinfection rather than operative mortality. Larger vegetations (> 2 cm) are a/w worse mortality.
Timing of surgery: no strict consensus on optimal timing but emergent = within 24 hours / urgent = within a few days / elective = after 1-2 weeks of antibiotic therapy. In general, early surgery is warranted for indications above and there is no advantage to delaying surgery

Left Ventricular Non-compaction

Today at morning report at the VA, we talked about left ventricular non-compaction:
– defined by prominent LV trabeculae (2:1 ratio of trabeculae to myocardial wall); deep intertrabecular recesses, and thin compacted layer.
Here are some echo images:
 
Here is a schematic to help you visualize what’s going on:
it is debated whether LVNC in adults is a distinct cardiomyopathy or an anatomic variant / morphologic trait shared by different types of cardiomyopathies. AHA classifies it as a genetic cardiomyopathy and it is associated with mutations in genes implicated in other genetic cardiomyopathies (ie HOCM). However, there is emerging evidence that pathogenic mechanisms leading to non-compaction or increased trabeculation may occur in adult life (found de novo in pregnant women, athletes, patients with sickle cell anemia).
– An important thing to note is that there are no genome-wide association studies because the challenge is that there are many phenotypic variants; so, a limitation of genetic studies is that most only screened genes associated with other cardiomyopathies (sarcomere mutations of HOCM).
– There is no gold standard for the diagnosis of LVNC, but TTE and cMRI with contrast are the best tools; if trabecula are biopsied, myocytes are histologically normal so biopsy is not part of the diagnostic work-up. Of note, it is common for either LV dilation or hypertrophy to be present and this does not influence the diagnosis but hypokinesis of non-trabeculated segments can strengthen the diagnosis of cardiomyopathy 2/2 LVNC. An important part of imaging is to distinguish true LVNC meeting criteria from hyper-trabeculation that is considered not pathologic.
Management
    – guidelines suggest that familial LVNC should be diagnosed by screening family members with TTE; genetic testing is not recommended routinely because does not change management
​- Patients are treated based on presence of cardiac dysfunction (ie GDMT for HFrEF) / arrhythmias
    ​- oral anticoagulation is administered to patients with LV dysfunction, proven thrombi, arrhythmias (atrial fibrillation is common) but debated in their absence
    – sudden cardiac death is a complication but not clear if this is related to the functional phenotype (reduced EF, HOCM) rather than LVNC itself. Clinical predictors for appropriate ICD therapy are not available
Find out more in this great review article: https://www.ncbi.nlm.nih.gov/pubmed/25443708