Afreen Shariff

Newly approved systemic treatment options for metastatic urothelial cancer (mUC) have diversified treatments and improved responses and survival for chemotherapy refractory disease. These systemic treatments have associated toxicities which need appropriate management for patients to stay on treatment and potentially have longer benefit from treatment. We review the expected toxicities of immune checkpoint inhibitors, FGFR inhibitors such as erdafitinib, and antibody drug conjugates such as enfortumab vedotin and sacituzumab govitecan.

OBJECTIVE: To describe a rare case of Wernicke encephalopathy (WE) as a result of hyperemesis gravidarum due to primary hyperparathyroidism (PHPT) in pregnancy. METHODS: We present the clinical presentation, supportive laboratory values, diagnostic dilemmas, treatment, clinical outcome, and supportive literature review of a patient with WE as a result of hyperemesis gravidarum due to PHPT in pregnancy. RESULTS: A 27-year-old previously healthy G1P0 female presented with initial symptoms of right upper-quadrant pain, nausea, vomiting, and paresthesias at 17.3 weeks of gestation. The patient later developed neurologic symptoms including acute encephalopathy, ataxia, and intranuclear ophthalmoplegia. The suspicion for WE was confirmed with characteristic findings on brain magnetic resonance imaging. WE was attributed to severe malnutrition from hyperemesis gravidarum and poor prenatal care. Hypercalcemia with an elevated parathyroid hormone level was identified following an unfortunate intrauterine fetal demise, raising suspicion for PHPT. PHPT was confirmed, and after undergoing successful parathyroidectomy, the patient regained normal neurologic function, with the exception of mild lower-extremity paresthesias. CONCLUSION: This case is an example where early recognition and treatment of hyperparathyroidism can be masked by severe malnutrition and present in an unusual way with neurologic symptoms of WE. Early recognition and suspicion are critical in preventing poor fetal outcomes and long-term consequences.

Objective: To describe a rare case of primary adrenal insufficiency (PAI) from immune checkpoint inhibitors (ICPIs). Methods: We describe the clinical presentation, supportive laboratory findings, long-term outcomes, and a review of the current available literature on PAI following administration of ipilimumab and nivolumab. Results: A 49-year-old Caucasian male with stage IIIB metastatic melanoma and failed standard chemotherapy and monotherapy with ipilimumab was started on nivolumab in addition to ipilimumab. Two months after starting the combination therapy, he presented with weakness, lethargy, nausea, and diarrhea for 1 to 2 weeks. Since there was a concern for treatment-associated endocrinopathy, an 8 AM cortisol and adrenocorticotrophic hormone (ACTH) were measured and noted to be 5.4 μg/dL (normal, 5 to 25 μg/dL) and 224 pg/mL (normal, 15 to 66 pg/mL), respectively. The cortisol was interpreted as normal, and follow-up was arranged in the endocrinology clinic. ACTH was drawn at the same time but reported after discharge. He presented again in 2 weeks with progressive symptoms, and a prestimulus cortisol was 1.6 μg/dL and 60 minutes after cosyntropin administration did not change, at 1.7 μg/dL. The patient was diagnosed with PAI based on additional data that included a plasma ACTH concentration of 827 pg/mL, elevated renin, and undetectable aldosterone with concurrent hyponatremia and hyperkalemia. He was treated with glucocorticoid and mineralocorticoid replacement and has since been in cancer remission. Conclusion: This case exemplifies how the diagnosis of a classic disease can be confounded in a complex patient and adds to the list of endocrinopathies from ICPI, where a high clinical suspicion should be maintained. Abbreviations: ACTH adrenocorticotrophic hormone anti-CTLA-4 Ab anti–cytotoxic T-cell antigen 4 antibody ICPI immune checkpoint inhibitor PAI primary adrenal insufficiency PD-1 programmed death 1 PDL-1 programmed death ligand 1

Background: We test a deep learning (DL) supported remote diagnosis approach to detect diabetic retinopathy (DR) and other referable retinal pathologies using ultra-wide-field (UWF) Optomap. Methods: Prospective, non-randomized study involving diabetic patients seen at endocrinology clinics. Non-expert imagers were trained to obtain non-dilated images using UWF Primary. Images were graded by two retina specialists and classified as DR or incidental retinal findings. Cohen's kappa was used to test the agreement between the remote diagnosis and the gold standard exam. A novel DL model was trained to identify the presence or absence of referable pathology, and sensitivity, specificity and area under the receiver operator characteristics curve (AUROC) were used to assess its performance. Results: A total of 265 patients were enrolled, of which 241 patients were imaged (433 eyes). The mean age was 50±17 years, 45% of patients were female, 34% had a diagnosis of diabetes mellitus type 1, and 66% of type 2. The average Hemoglobin A1c was 8.8±2.3%, and 81% were on Insulin. Of the 433 images, 404 (93%) were gradable, 64 patients (27%) were referred to a retina specialist, and 46 (19%) were referred to comprehensive ophthalmologist for a referable retinal pathology on remote diagnosis. Cohen's kappa was 0.58, indicating moderate agreement. Our DL algorithm achieved an accuracy of 82.8% (95% CI: 80.3-85.2%), a sensitivity of 81.0% (95% CI: 78.5-83.6%), specificity of 73.5% (95% CI: 70.6-76.3%), and AUROC of 81.0% (95% CI: 78.5-83.6%). Conclusions: UWF Primary can be used in the non-ophthalmology setting to screen for referable retinal pathology and can be successfully supported by an automated algorithm for image classification.