Faculty Bibliography

A 49-year-old woman with cholangiocarcinoma metastatic to the lungs presented with new-onset unrelenting headaches. A lumbar puncture revealed malignant cells consistent with leptomeningeal metastasis from her cholangiocarcinoma. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal enhancement. An intrathecal (IT) catheter was placed and IT chemotherapy was initiated with methotrexate. Her case is notable for the rarity of cholangiocarcinoma spread to the leptomeninges, the use of IT chemotherapy with cytologic and potentially symptomatic response, and a possible survival benefit in comparison to previously reported cases of leptomeningeal carcinomatosis secondary to cholangiocarcinoma.

LEARNING OBJECTIVE 1: Recognize and distinguish the clinical features of drug-induced hepatitis from other etiologies of hepatitis LEARNING OBJECTIVE 2: Manage acute drug-incuded hepatitis with concomitant hepatitis C infection CASE: A 61 year-old Hispanic female presented with jaundice, dark urine and progressive fatigue of three weeks duration. The patient presented to her primary care physician three weeks prior to admission with bloating and early satiety, and was started on rabeprazole 20 mg daily. After one week, blood tests were drawn which were notable for an AST/ ALT of 1680/1123 u/L, alkaline phosphatase of 283 u/L, and total bilirubin of 1.7 mg/dL. The patient subsequently noted worsening abdominal discomfort, fatigue and jaundice. She was referred for an endoscopy that demonstrated severe gastritis. The patient was then prescribed omeprazole 40 mg daily and ranitidine 20 mg daily, with discontinuation of rabeprazole. Due to progression of her symptoms the patient presented to our hospital where she was found to have an AST/ALT of 3423/1620 u/L, alkaline phosphatase of 269 u/L, total bilirubin 10 mg/dL, and a direct bilirubin 6mg/dL. Physical exam was significant for jaundice, icteric sclera, and mild right upper quadrant pain. A CAT scan of the abdomen and pelvis demonstrated several small hepatic cysts, but was otherwise normal. The patient's medications including omeprazole were held, and her hepatic enzymes subsequently improved, which was suggestive of a diagnosis of drug-induced hepatitis. In addition, workup of the patient's liver function abnormalities revealed a positive hepatitis C antibody and viral load of 7x 10 6 copies/mL. Due to suspicion of acute hepatitis C versus drug-induced hepatitis, a liver biopsy was performed which was significant for acute drug induced hepatitis intermixed with elements of chronic hepatitis C. DISCUSSION: In cases of acute hepatitis of unclear etiology, medications should always be considered as possible culprits and reviewed thoroughly. Alth!

OBJECTIVES: Many randomized clinical trials (RCTs) are labelled efficacy and safety while due consideration for power is provided only for efficacy outcomes. This in turn necessitates a discussion of the inadequacy of sample size (type II error) for identifying harm. This is particularly important in RCTs of TNF inhibitors as harm related to these agents is still a matter of debate. METHODS: PubMed was searched for all RCTs published examining TNF inhibitors in RA, PsA and AS. Only original study reports were surveyed for whether: (i) they were labelled as efficacy, safety or both; (ii) the methods sections included safety as a primary or secondary end point; (iii) power calculations were adequately explained; (iv) statistical tests of significance were given for harm; and finally (v) any discussion of type II error for harm was present. RESULTS: Of the 34 articles surveyed, 24 (71%) were labelled as efficacy and safety. Among these, 23 (96%) did not include safety as a formal primary or secondary end point. In only 2/24 (8%) power calculations were given for safety. Finally, in only 3/22 (14%) any discussion about the inadequate sample size (type II error) for detecting harm could be found. CONCLUSIONS: Most reports of RCTs of TNF inhibitors in rheumatological diseases are inappropriately labelled as addressing efficacy and safety. Their lack of power in detecting harm is not adequately discussed, either.