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Background Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis. First-line multikinase inhibitors like sorafenib and lenvatinib are poorly tolerated and have low response rates. Several clinical trials have shown tolerability and efficacy of immunotherapy in this setting. The objective of this retrospective study was to determine the outcomes of front-line nivolumab in a frail real-world population. Observations In this retrospective study conducted between January 2016 and December 2019, 14 men (median age, 63.5 years; range, 58-72 years) with HCC received nivolumab as front-line systemic therapy. Only 2 patients had a response to immunotherapy (14.3%), of which 1 patient had a complete response (7.1%). The median progression-free survival was 4 months and median overall survival was 8 months. Incidence of grade 3 or higher toxicity was 35%. Conclusions In our small, real-world cohort of patients receiving immunotherapy as front-line systemic treatment for HCC, outcomes were poor with front-line immunotherapy.

Hepatic sinusoidal obstruction syndrome (SOS) has been reported in patients receiving high dose intravenous (IV) cyclophosphamide especially as a part of preparative regimen for hematopoietic stem cell transplantation. Hepatic SOS from low dose oral cyclophosphamide has not been reported. Here we present a rare case of hepatic SOS induced by low dose oral cyclophosphamide. A 78-year-old male with history of coronary artery disease status post coronary artery bypass graft (CABG) was initially seen in hematology clinic for evaluation of normocytic anemia. During workup, bone marrow biopsy revealed NK cell large granular lymphocytic leukemia (LGL). He was then started on low dose oral cyclophosphamide 50 mg daily. After 2 months, his dose was reduced to 25 mg daily due to severe neutropenia. He then tolerated cyclophosphamide well and his hemoglobin (Hb) improved from his baseline 8 gm/dl to 12 gm/dl in 4 months. After 6 months of treatment, he was admitted to the hospital for abdominal distension, ascites and 15 pounds weight gain over 3 weeks. Labs most prominent on admission were Hb of 12.5 gm/dL , WBC 5.3 x 103/µL, Platelets 197 x 103/µL, total bilirubin 1.6 mg/dL, aspartate aminotransferase (AST) 89 U/L , alanine aminotransferase (ALT) 35 U/L and alkaline phosphatase (ALP) 283 U/L. Workup of ascites included abdominal paracentesis which revealed serum ascites albumin gradient(SAAG) High dose of IV cyclophosphamide given as myeloablative therapy in combination of total body irradiation or busulfan (or other agents) in preparation for hematopoietic stem cell transplantation can induce hepatic SOS, which can be severe leading to acute liver failure and death. The diagnosis is usually based on clinical features of tender hepatomegaly, weight gain, ascites and jaundice. Liver biopsy is usually diagnostic. Mechanism of injury is related to direct toxic effects of cyclophosphamide on sinusoidal cells in the liver, causing their necrosis and release into the sinusoids, obstruction and obliteration of hepatic veins. This case demonstrates that hepatic SOS can also be caused by low dose oral cyclophosphamide. Given this rare occurrence, it is prudent for the clinicians to keep an open mind and consider hepatic SOS as a potential side effect even with oral cyclophosphamide. Disclosures Yacoub: Novartis: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Hylapharm: Current equity holder in private company; Cara Therapeutics: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Dynavax: Current equity holder in publicly-traded company; Roche: Other: Support of parent study and funding of editorial support.

Thrombocytopenia is an uncommon side effect of trimethoprim/sulfamethoxazole (TMP/SMX) when given in the usual recommended adult dosage. We report a case of severe and possibly life-threatening thrombocytopenia associated with TMP/SMX therapy. A 92-year-old female presented after a mechanical fall and subsequent intractable bleeding from a laceration on her left leg. She had a history of cellulitis of the lower extremities treated with a 10-day course of TMP/SMX. Her last dose was two days before the visit. The physical examination was significant for a small laceration on her left shin, with persistent oozing of blood. Her blood work was notable for white blood cells (WBC) 9.4×10^9/L (9.4×10^3/mm^3), hemoglobin 125g/L (12.5 g/dL) and platelets 5×10^9/L (5×10^3/mm^3). A repeat platelet count was 4×10^9/L. Prothrombin time was 11 seconds and the international normalized ratio (INR) was one. The TMP/SMX was discontinued and one unit of platelets was transfused. Her platelet count subsequently increased to 108×10^9/L. Severe thrombocytopenia with a platelet count of ≤10×10^9/Lmay rarely result in the catastrophic spontaneous bleeding. Thus, low platelet counts associated with TMP/SMX carry potential life-threatening complications. The clinicians should be aware of this adverse effect of TMP/SMX, which appears to be dose/duration independent. We suggest careful monitoring of complete blood cell count, especially platelet count, before and during TMP/SMX therapy.

Anti-N-methyl-D-aspartate-Receptor (NMDAR) encephalitis is an autoimmune disorder with a multifaceted presentation that involves memory deficits, psychiatric symptoms, and autonomic instability. This case report describes the classic presentation of Anti-NMDAR encephalitis and highlights its association with ovarian teratomas. We present a 26 -year-old female who came in with new onset seizures and altered mentation who subsequently developed automatism. Electroencephalograms (EEG) showed left frontal spikes and right temporal delta activity. Magnetic resonance imaging (MRI) revealed right temporal hyper-intensity. The diagnosis was established with positive anti-NMDAR antibodies in the cerebrospinal fluid (CSF). The patient was initially treated with steroids and valproic acid, however, her condition progressively worsened. A five-day course of intravenous immunoglobulins (IVIG) was started followed by rituximab. The clinical course was complicated with the patient developing neutropenic fever and cerebrospinal fluid cultures (CSF) growing methicillin-sensitive Staphylococcus aureus (MSSA). She underwent pelvic imaging which showed a right ovarian teratoma. Evidence suggests that removal of ovarian tumor leads to better clinical and mortality outcomes in patients with Anti-NMDAR encephalitis. It is important for the internist to consider paraneoplastic syndromes in patients with Anti-NMDAR encephalitis.