The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with its expression on the surface of supporting cells in the inner ear, CTL2 contains 10 predicted membrane-spanning regions with multiple N-glycosylation sites. The 68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the transporter function of this molecule. CTL2 mRNA and protein are abundantly expressed in human inner ear. Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans.

e19098 Background: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency. Spontaneous TLS (STLS) in solid tumors occurring prior to initiation of therapy is a rarely reported entity and has poor outcomes. Little is known about the prognostic factors influencing STLS in solid tumors. Methods: A systematic search of Medline, PubMed, and Embase was conducted to identify reports of patients ≥18 years diagnosed with STLS in solid tumors. Individual case reports and case series were summarized, and descriptive statistics were employed to report clinical outcomes. Fischer exact t test was used for statistical analysis. Results: 63 patients from 61 case reports and one patient from our institution resulted in a total of 64 patients. 53.1% were males with a median age of 56.1 years. The most common solid tumors were of pulmonary origin. 85.9% patients had stage 4 malignancy, 75.0% had hepatic involvement. The most common presenting symptom was abdominal discomfort. The mean serum potassium, phosphorus, uric acid, calcium, lactate dehydrogenase, and creatinine upon presentation were 6.1 mmol/l, 7.5 mg/dl, 16.4 mg/dl, 7.5 mg/dl, 4421.2 IU/L and 3.7 mg/dl, respectively. In addition to intravenous hydration, allopurinol and rasburicase were administered in 48.4% and 42.2% patients. Urinary alkalization and sodium bicarbonate administration were reported in 6.3% and 15.6% patients. 43.8% patients required hemodialysis and 39 patients died (mortality of 60.9%). Patients who underwent hemodialysis had a similar mortality of 60.4%. We assessed liver involvement (primary hepatocellular carcinoma and hepatic metastasis) as a potential prognostic factor. Compared to patients without liver involvement, patients with liver involvement had a higher unadjusted all-cause mortality (70.83% vs 25%; OR 7.29 [95% CI 1.71 - 30.98]; p = 0.006). Conclusions: Hepatic involvement is a potential prognostic factor for STLS in solid tumors and is associated with a grave prognosis. Future large prospective studies are needed to probe into the role of early hemodialysis and to identify other prognostic factors of STLS in solid tumors.

Bevacizumab (BV) is a humanized monoclonal antibody that inhibits angiogenesis by targeting vascular endothelial growth factor (VEGF). The addition of BV to combination chemotherapy has been shown to improve the outcomes in several malignancies, including colorectal carcinoma (CRC). However, the use of BV has been associated with adverse effects, including hypertension, hemorrhage, proteinuria, delayed wound healing and bowel perforation. Pneumothorax (PTX) as an adverse event associated with BV use has rarely been reported. We herein report the case of a 68-year-old female patient with a history of metastatic CRC treated with combination chemotherapy, including BV, who presented with complaints of shortness of breath and was found to have a right-sided PTX.