EUH Morning Report: Should lasix (furosemide) be considered in the setting of hypercalcemia?

The Bottom Line: Avoid loop diuretics in the setting of acute hypercalcemia, except it may be considered for patients with concomitant volume overload.

DynaMed Plus provides the following information on loop diuretics:

  • inhibits calcium resorption in distal renal tubule
  • may worsen volume depletion and electrolyte derangements and should be used with caution
  • no evidence to support use in acute hypercalcemia
    • may be used to control volume overload
    • associated with hypokalemia and possibly contributes to dehydration

References: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 116018, Hypercalcemia; [updated 2016 Dec 27, cited 2018 Jul 19]; [about 10 screens]. Emory login required.

LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine. 2008;149(4):259-263.

Summary: The following is a review of LeGrand et al’s 2008 article (NEJM Journal Watch):

A literature review found little support for the use of the diuretic furosemide to treat hypercalcemia.

Many textbooks recommend saline and furosemide as first-line management for hypercalcemia. Investigators searched the literature since 1950 for studies of furosemide or bisphosphonate use for hypercalcemia in people.

They identified nine reports — the most recent from 1983 — involving 37 patients treated with furosemide for hypercalcemia; doses ranged from 240 mg to 2400 mg. Calcium normalized in 14 of 39 episodes, and within 12 hours in only two cases. Intensive monitoring was accompanied by replacement of fluid and electrolyte losses. Complications included hypernatremia, coma, metabolic acidosis, hypophosphatemia and hypomagnesemia, altered mental status, and tetany.

Investigators identified 56 clinical studies of bisphosphonates — 34 were randomized and included more than 1000 patients. In a systematic review of 26 studies of bisphosphonate use in hypercalcemia of cancer, calcium levels normalized in more than 70% of patients. The authors conclude that volume repletion and bisphosphonate therapy should be the standard management strategy for hypercalcemia, with furosemide used only for managing fluid overload.


Forced saline diuresis for hypercalcemia is a long-standing practice that persists, even in authoritative texts, despite the absence of evidence for its efficacy, the existence of known risks, and the availability of other proven treatments. Saline and bisphosphonates, with or without calcitonin, are the standard of care for hypercalcemia.

Posted in EUH, Teaching pearls, Therapy

EUH Morning Report: What is the criteria for liver transplantion in patients with hepatocellular carcinoma?

The Bottom Line: Liver transplant is recommended for patients with potentially resectable or transplantable disease according to performance status or lack of severe comorbidity, or in patients with unresectable disease who meet Milan or United Network for Organ Sharing (UNOS) criteria. Controversy exists over liver transplantation in patients with tumors marginally outside Milan or UNOS criteria, but some institutions may still consider it (DynaMed Plus, 2017).

  • Milan criteria for liver transplantation for hepatocellular carcinoma includes either of:
    • single lesion ≤ 5 cm in diameter
    • 2-3 lesions all ≤ 3 cm in diameter
  • UNOS criteria for liver transplantation for hepatocellular carcinoma includes both of:
    • Milan criteria
    • no evidence of macrovascular involvement or extrahepatic disease

Reference: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 909499, Management of early hepatocellular carcinoma / Liver Transplant; [updated 2017 May 31, cited 2018 June 28]; [about 24 screens]. Emory login required.


(DynaMed Plus, 2017)

Posted in Applying evidence, EUH, Morning Report, Therapy | Tagged ,

EUH Morning Report: Review of type 1 vs type 2 hepatorenal syndrome

The Bottom Line: Hepatorenal syndrome (HRS) is functional renal impairment in patients with advanced liver disease and without evidence of renal parenchymal disease, severe volume loss, or nephrotoxicity from medication.

    • type 1 hepatorenal syndrome
      • rapid decline in renal function
      • doubling of serum creatinine from baseline to > 2.5 mg/dL (221 mcmol/L) in < 2 weeks
      • usually triggered by precipitating event causing both a decline in liver function as well as a decline in other organ functions leading to hepatorenal syndrome
    • type 2 hepatorenal syndrome
      • steady, progressive decline in renal function (average serum creatinine 2 mg/dL [176.8 mcmol/L])
      • usually characterized by refractory ascites and sodium retention

Reference: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 116729, Hepatorenal syndrome; [updated 2018 May 30, cited 2018 June 28]; [about 15 screens]. Emory login required.

Posted in Background question, EUH, Morning Report

EUH Morning Report: What is Sister Mary Joseph’s nodule?

The Bottom Line: Sister Mary Joseph’s nodule is a metastatic cancer of the umbilicus that is typically associated with adult cancers of the gastrointestinal tract and ovary (Albano and Kanter, 2005). It is a rare but important physical finding and is a sign of advanced stage of malignancy (Tso et al, 2013).

References: Albano EA, Kanter J. Sister Mary Joseph’s Nodule. N Engl J Med. 5 May 2005;352(18):193.

Tso S, Brockley J, Recica H, Ilchyshyn A. Sister Mary Joseph’s Nodule: an unusual but important characteristic of widespread internal malignancy. Br J Gen Pract. 2013 Oct;63(615):551-552. Doi: 10.3399/bjgp13X673900.

Summary: The condition is named after Sister Mary Joseph (1856-1939), a surgical assistant for Dr. William Mayo, who noted the association between paraumbilical nodules observed during skin preparation for surgery and metastatic intraabdominal cancer confirmed at surgery (Albano and  Kanter, 2005).

Posted in Background question, EUH, Teaching pearls | Tagged

EUH Morning Report: What is the rational clinical exam for ascites?

The Bottom Line: The examiner should ask about recent ankle edema, weight gain, or change in abdominal girth. Other potentially important items are a history of liver disease or congestive heart failure. The focused physical exam includes: (1) inspection for bulging flanks, (2) percussion for flank dullness, (3) a test for shifting dullness, and (4) a test for a fluid wave (Williams and Simel, 1992).


References: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 116330, Ascites; [updated 2017 Jul 31, cited 2018 Jun 22]; [about 20 screens]. Emory login required.

Williams JW Jr, Simel DL. The rational clinical examination. Does this patient have ascites? How to divine fluid in the abdomen. JAMA. 1992 May 20;267(19):2645-8.

Summary: Ascites is a symptom that may have important diagnostic, prognostic, and therapeutic implications. When clinically detectable, ascites may indicate underlying heart failure, liver disease, nephrotic syndrome, or malignancy (Williams & Simel, 1992).

Skin: assess for signs of liver disease

  • Jaundice
  • Spider veins
  • Palmar erythema
  • Caput medusa (abdominal wall collateral veins)


  • Jugular venous distention may be present secondary to heart failure


  • Look for associated pleural effusions (dependent rales)


  • Abdominal distention
  • Fluid wave
  • Shifting dullness
  • Umbilicus eversion
  • Low umbilicus position (Tanyol sign)
  • Flank dullness
    • About 1,500 mL of fluid must be present to be detected
    • If no flank dullness, patient has < 10% chance of ascites


  • Look for associated peripheral edema
  • Leukonychia (white nails) may be seen in advanced liver disease


  • Penile or scrotal edema may be seen

(DyanMed Plus, 2018)

Posted in Diagnosis, EUH | Tagged

New Intern Orientation: Adjusted ASCVD Risk

The Bottom Line: Major guidelines recommend that decisions about aspirin, blood pressure, and statin treatments be informed by 10-year CVD risk estimates from the PCEs, which were derived in 2013 using data from 5 cohort studies. These PCEs are controversial because of reports that they substantially misestimate risk. Two basic strategies to revise the PCEs could improve their accuracy: updating the data from which they are derived and changing the statistical methods used to derive them (Yadlowsky et al, 2018).

In his review of the recent study by Yadlowsky et al (2018), Dr. Dan Dressler provides the following example: Assume the patient is a 68-year-old white man with the following favorable risk profile: Total cholesterol, 160 mg/dL; HDL cholesterol, 55 mg/dL; blood pressure, 120/70 mm Hg; and no history of diabetes, hypertension, or smoking. His 10-year CVD risk is 12% on the ACC/AHA calculator, but only 6% on this new model’s calculator. The latter risk is below the threshold at which most clinicians would recommend statin therapy (Dressler, 2018).

References: Dressler DD. 10-year cardiovascular risk might be lower than we thought. NEJM Journal Watch. 2018 Jun 21.

Yadlowsky S, Hayward RA, Sussman JB, McClelland RL, et al. Clinical implications of revised pooled cohort equations for estimating atherosclerotic cardiovascular disease risk. Ann Intern Med. 2018 Jun 5. doi:10.7326/M17-3011

Summary: The clinical implications of the results suggest that the revised PCEs will reduce overestimation of risk in general and may prevent adverse events, health care costs, and inflated expectations of absolute risk and corresponding absolute therapeutic benefit. Additionally, use of the updated equations will correct erroneous, implausible risk estimates for many African American adults (Yadlowsky et al, 2018).

The study by Yadlowskey et al (2018) validates what some clinicians have observed in practice: Some patients are classified inaccurately as “high risk.” Although guidelines that depend on risk calculation would not necessarily need to change if risk calculators are updated, the number of patients who would be affected by guideline recommendations could be lowered dramatically (Dressler 2018).

Posted in Diagnosis, EUH | Tagged

EUH Krakow Conference: What are risk factors for cryptococcus gattii?

The Bottom Line:  The risk factors for acquiring cryptococcus gattii are:

  • Age > 50 years
  • History of smoking
  • Corticosteroid use
  • HIV infection
  • History of cancer
  • History of chronic lung disease


References: MacDougall L, Murray F, Romney M, Starr M, et al. Risk factors for Cryptococcus gattii infection, British Columbia, Canada. Emerg Infect Dis. 2011 Feb;17(2):193-199. Doi:10.3201/eid1702.101020

Bartlett KH, Cheng PY, Duncan C, Galanis E, et al. A decade of experience: Cryptococcus gattii in British Columbia. Mycopathologia. 2012 Jun;173(5-6):311-9. Doi:10.1007/s11046-011-9475-x.

Summary: Cryptococcus gattii is commonly believed to infect those with healthy immune systems, yet several immunosuppressive and pulmonary conditions seem to be risk factors (MacDougall et al, 2011).

Posted in Diagnosis, EUH | Tagged