What is the Milan Criteria for liver transplantation?

The Bottom Line: The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas (HCC) and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors.

References: Mazzaferro V., et al. “Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.” New England Journal of Medicine 1996 Mar 14; 334(11): 693-699.

Mazzaferro V., et al. “Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience.” Liver Transplantation 2011 Oct; 17 (Suppl 2): S44-S57 .

Summary:   The original prospective cohort study simply concluded that “liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis” (1996, p.693). Named for its origin in Milan, Italy, the Milan criteria (MC) have since become a standard practice of care in treatment of patients with HCC. Ever since their adoption in clinical practice, the MC have helped doctors to single out early-stage HCC as a prognostic category of cancer presentation that is amenable to curative treatments. After their implementation, the favorable posttransplant outcomes that were observed in cohort series were so convincing that the MC immediately became the standard of care for early HCC, and further validation by randomized controlled trials (RCTs) was prevented.


Posted in Applying evidence, Background question, EUH

Vitamin k administration routes for prevention of thrombosis

Bottom line: Evidence that is of low and moderate quality, respectively, is used in a guideline that recommends against routine vitamin K supplementation for patients taking vitamin K antagonists (VKAs) (grade 2c) and against routine vitamin K supplementation for patients taking VKAs with international normalized ratios (INRs) between 4.5 and 10 and no evidence of bleeding (grade 2b). Low-quality evidence resulted in a guideline recommendation of oral vitamin K for patients taking VKAs with INRs > 10 with no evidence of bleeding (grade 2c) and of the additional use of a slow IV injection rather than reversal with coagulation factors alone for patients with VKA-associated major bleeding (grade 2c) (Holbrook et al., 2012).


Holbrook, A., Schulman, S., Witt, D., Vandvik, P., Fish, J., Kovacs, M., . . . Guyatt, G. (2012). Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2 Suppl), E152S-E184S.

Crowther, M., Douketis, J., Schnurr, T., Steidl, L., Mera, V., Ultori, C., . . . Ageno, W. (2002). Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial. Annals of Internal Medicine, 137(4), 251-254.

Raj, G., Kumar, R., & McKinney, W. (1999). Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione. Archives of Internal Medicine., 159(22), 2721-2724.

Rivosecchi, R., Garavaglia, J., & Kane-Gill, S. (2015). An evaluation of intravenous vitamin k for warfarin reversal: Are guideline recommendations being followed? Hospital Pharmacy., 50(1), 18-24.

Guyatt, G., Cook, D., Jaeschke, R., Pauker, S., & Schünemann, H. (2008). Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest., 133(6 Suppl), 123S-131S.


Literature states that IV vitamin K is effective more rapidly in reversing anticoagulation than oral and subcutaneous vitamin K routes (Raj, Kumar, & McKinney, 1999; Rivoscchi, Garavaglia, & Kane-Gill, 2015), and oral vitamin K is effective more rapidly than subcutaneous vitamin K (Crowder et al, 2002). Different routes have different issues. Commentary on whether the 9th edition of the guidelines are being followed states, “Subcutaneous injection is generally not recommended due to erratic absorption and unpredictable results….Intravenous administration requires the medication to be given over 30 minutes, which could prevent other medications from being administered…anaphylaxis…approximately 3 cases per 10,000 administrations…remains a risk that must be considered…if anticoagulation is reversed to below subtherapeutic levels unnecessarily, patients are at risk for thrombotic events until anticoagulation is resumed” (Rivoscchi, Garavaglia, & Kane-Gill, 2015).

Explanations of grades that were provided with 8th edition of American College of Chest Physicians’ guidelines state: “Grade 2 recommendation. For grading methodologic quality, randomized controlled trials (RCTs) begin as high-quality evidence (designated by “A”), but quality can decrease to moderate (“B”), or low (“C”) as a result of poor design and conduct of RCTs, imprecision, inconsistency of results, indirectness, or a high likelihood for reporting bias. Observational studies begin as low quality of evidence (C) but can increase in quality on the basis of very large treatment effects. Strong (Grade 1) recommendations can be applied uniformly to most patients. Weak (Grade 2) suggestions require more judicious application, particularly considering patient values and preferences and, when resource limitations play an important role, issues of cost” (Guyat, Cook, Jaeschke, Pauker, & Schunemann, 2008).

Posted in EUH, Therapy | Tagged

Long-term versus short-term anticoagulation post ablation in patients with atrial fibrillation (a fib)/atrial flutter

Bottom line: “Observational data suggest that successfully ablated atrial fibrillation patients have very low rates of stroke (<0.7% per year) despite cessation of OAC [oral anticoagulation] after ablation. High-quality, randomized clinical trials are needed to address whether long-term OAC use may be obviated in patients who have had successful atrial fibrillation ablation.”[1] “CHADS2 and CHA2DS2-VASc scores could be used to identify patients at the risk of TE events after ablations who should continue OACs despite the status of recurrence” of thromboembolic (TE) events.[2]


  1. Ha, A., Hindricks, G., Birnie, D., & Verma, A. (n.d.). Long-term oral anticoagulation for patients after successful catheter ablation of atrial fibrillation: Is it necessary? Current Opinion in Cardiology, 30(1), 1-7.
  2. Chao, T., Lin, Y., Chang, S., Lo, L., Hu, Y., Chung, F., . . . Chen, S. (n.d.). Can oral anticoagulants be stopped safely after a successful atrial fibrillation ablation? Journal of Thoracic Disease, 7(2), 172-177.
Posted in Background question

Treatment of insulinoma

The Bottom Line: Treatment of insulinoma consists of controlling symptoms of hypoglycemia, followed by tumor localization.

Neuroendocrine Tumors
Jensen, Robert T., Norton, Jeffrey A., Oberg, Kjell
Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Chapter 33, Pages 501-541.e15
Copyright © 2016 by Saunders, an imprint of Elsevier Inc.
https://www.clinicalkey.com/#!/content/3-s2.0-B9781455746927000338 (click on “Treatment” in the menu on the left)

Hypoglycemia is controlled in most insulinoma patients by a combination of dietary and pharmacologic therapy. Snack intake should not be restricted to rapidly absorbed carbohydrates, because their ingestion may occasionally stimulate insulin secretion from the tumor.

If liver metastases are not present on imaging studies (>90% of cases), surgical exploration and resection (if possible) are indicated in patients with insulinomas. Anywhere from 70% to 97% of patients are cured by surgery.

Posted in VA | Tagged

Conditions exhibiting fever without tachycardia/causes of fever with relative bradycardia

Bottom line:

Conditions exhibiting fever without tachycardia/causes of fever with relative bradycardia (listed in alphabetical order):  babesiosis, beta blockers, brucellosis (combination of signs is not common), central nervous system (CNS) lesions, Chagas’ disease, Coxiella burnetii, cytomegalovirus heterophile-negative mononucleosis, dengue fever, digitalis, drug fever, Ehrlichia canis, factitious fever, legionella, leptospirosis, lymphomas, acute malaria, meningococcemia and meningitis, mycoplasma, pheochromocytoma, pneumonia caused by Chlamydia sp., pneumonia caused by mycoplasma (combination of signs is not common), psittacosis, Q fever, respiratory syncytial virus (RSV), acute rheumatic fever, Rift Valley fever, Rocky Mountain spotted fever, Salmonella typhimurium, sepsis, typhoid fever (combination of signs is rare; also known as enteric fever), typhus, viral hemorrhagic fevers, yellow fever


Posted in Diagnosis, EUH | Tagged

Sources for syncope rules

Evaluation of Guidelines in Syncope Study (EGSYS) syncope score: Calculate by QxMD (app is freely available for Android and Apple devices), EMERG CDRs (app is freely available for Android devices)

Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score: American Family Physician (AFP, see Table 1)

Risk Stratification of Syncope in the Emergency Department (ROSE) risk score: AFP (see Table 1)

San Francisco Syncope Rule: AFP (see Table 1), CliniCalc (app is freely available for Apple devices), MDCalc, MediCalc® (app is freely available for Android and Apple devices), Omnio (app is freely available for Android and Apple devices)

Syncope Risk Prediction (similar to OESIL tool): DynaMed Plus (click here for instructions)

Posted in Applying evidence, EUH, Miscellaneous

The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) Study

The Bottom Line: The effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. This RCT concluded that bloodpressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge.

Reference: He, Jiang, Zhang, Yonghong, Xu, Tan, Zhao, Qi, Wang, Dali, Chen, Chung-Shiuan, Tong, Weijun, Liu, Changjie, Xu, Tian, Ju, Zhong, Peng, Yanbo, Peng, Hao, Li, Qunwei, Geng, Deqin, Zhang, Jintao, Li, Dong, Zhang, Fengshan, Guo, Libing, Sun, Yingxian, Wang, Xuemei, and Cui, Yong. “Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients with Acute Ischemic Stroke: The CATIS Randomized Clinical Trial.JAMA the Journal of the American Medical Association. 311.5 (2014): 479-89.

For Additional Reading: Gorelick, Philip B. “Should Blood Pressure be Lowered in Acute Ischemic Stroke? The CATIS Trial.” Journal of American Society of Hypertension 9.5 (2015):331-333.

Ivanov A, Mohamed A, Korniyenko A. “Permissive Hypertension In Acute Ischemic Stroke: Is It a Myth or Reality?Journal of the American College of Cardiology. 65.10S (2015). doi:10.1016/S0735-1097(15)61344-4.

Posted in Applying evidence, Background question, EUH | Tagged ,