Case Report: Successful treatment of late-onset immune checkpoint inhibitor-associated membranous nephropathy in a patient with advanced renal cell carcinoma.

Background: Diagnosing immune checkpoint inhibitor (ICI)-associated nephritis can be challenging since it is a rare complication of therapy, associated with a spectrum of immune-mediated pathologies, and can present months after ICI therapy discontinuation (i.e., late-onset). ICIs are increasingly administered in combination with other cancer therapies with associated nephrotoxicity, further obfuscating the diagnosis of ICI-associated nephritis. In this report, we describe the first suspected case of late-onset ICI-associated membranous nephropathy (MN) in a patient with metastatic clear cell renal cell carcinoma (RCC) who had discontinued ICI therapy 6 months prior to presentation. Prompt recognition of the suspected late-onset immune-related adverse event (irAE) resulted in the successful treatment of MN and continuation of RCC therapy. Case presentation: A 57-year-old man with metastatic clear cell RCC was responsive to third-line RCC therapy with lenvatinib (oral TKI) and everolimus (oral mTOR inhibitor) when he presented with nephrotic range proteinuria and acute kidney injury (AKI). His kidney biopsy revealed probable secondary MN with subendothelial and mesangial immune complex deposits and negative staining for both phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A). While a diagnosis of paraneoplastic MN could not be excluded, the patient was responding to cancer therapy and had tumor regression. However, 6 months prior to presentation, the patient had received pembrolizumab, an ICI, with his first-line RCC treatment. Due to concern that the patient may be presenting with late-onset ICI-associated MN, he was effectively treated with rituximab, which allowed for his continued RCC therapy. Conclusion: This report highlights the first case of suspected late-onset ICI-associated MN and the increasing complexity of recognizing renal irAEs. With the growing indications for the use of ICIs in combination with other cancer therapies, recognizing the various presentations of ICI-immune nephritis can help guide patient management and treatment.

Real-time Quaking-induced Conversion Assay for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease in a Living Patient.

Creutzfeldt-Jakob disease (CJD) is the most common prion disease in humans with an incidence of one case per million inhabitants worldwide. The sporadic form of CJD (sCJD) is spontaneous and accounts for 85% of cases. Its symptoms include rapidly progressive dementia, ataxic gait, personality changes, myoclonus, coma, and eventually death. The challenging diagnosis is currently made by a combination of clinical criteria and supporting tests such as electroencephalography (EEG), magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) studies. These modalities can be falsely positive or negative in some cases. Therefore, true confirmation usually requires a postmortem brain biopsy. We present a case of a 58-year-old woman who was diagnosed with sporadic form CJD by the novel Real-time Quaking-induced Conversion (RT-QuIC) assay. It is based on an ultrasensitive detection of the pathogenic prion protein in the CSF that directly detects a prion protein rather than a surrogate marker of neurodegeneration such as 14-3-3 or tau protein. The RT-QuIC assay has emerged as the most sensitive and specific CSF study to accurately diagnose sCJD in a living patient, without the need for invasive brain biopsy. The emergence of the nasal brushing RT-QuIC assay may further revolutionize the future of combating prion diseases.

Case Report: Kryptonite-A Rare Case of Left-Sided Bilothorax in a Sickle Cell Patient.

Bilothorax is a rare cause of an exudative pleural effusion. The diagnosis is confirmed by a pleural fluid to serum bilirubin ratio of greater than 1. Typically, bilothorax presents as a right-sided effusion due to its proximity to the liver and biliary system. Herein, we present a case of isolated left-sided bilothorax in a 43-year-old female admitted with sickle cell crisis. Only one other case of isolated spontaneous left-sided bilothorax has been described in the literature. A thoracentesis performed on admission demonstrated greenish fluid and bilothorax was suspected, with a pleural fluid to serum bilirubin ratio greater than 1 confirming the diagnosis. A magnetic resonance cholangiopancreatography (MRCP) showed an abnormal 90-degree acute angulation in the mid-to-distal common bile duct with proximal common bile duct and intrahepatic bile ducts dilation. This was further confirmed with an endoscopic retrograde cholangiopancreatography (ERCP), which did not reveal any extravasation of contrast into the left pleural space. Ultimately, despite the use of various modalities, no definitive cause of bilothorax was identified. Postthoracentesis imaging revealed evidence of fibrothorax, a direct and permanent complication of bilothorax. The presence of an isolated left-sided bilothorax, along with the lack of a confirmed etiology, makes this case unique.