Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking. Methods: We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively. Results: Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR) < 15 ml/min per 1.73 m2 and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m2 with a mean (SD) change of +12 (25) and +20 (23) ml/min per 1.73 m2 at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%). Conclusion: A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.

Obstructive jaundice, a rare presentation of lung cancer: A case report.

Lung cancer metastases to the pancreas are rare but potentially life-threatening. Oftentimes, the presence of symptoms is indicative of extensive disease burden. This report describes a case of primary lung adenocarcinoma metastasizing to the head of the pancreas presenting as obstructive jaundice. The patient was a 61-year-old female veteran who presented with a chronic dyspnea, weight loss, and 3-weeks of nausea and vomiting found to have jaundice, elevated alkaline phosphatase levels, hyperbilirubinemia, and transaminitis. Imaging of her chest revealed large pulmonary parenchymal nodules throughout both lungs with a large left lower lobe mass and consolidation. Abdominal imaging showed a large heterogeneous mass in the pancreatic head, a grossly dilated common bile duct, and enlarged retroperitoneal lymph nodes contiguous with the mass. Pancreatic head biopsies revealed metastatic cancer cells from her lung adenocarcinoma which was confirmed via cytology and the presence of thyroid transcription factor - 1 and cytokeritin-7 expression and the absence of tumor protein 63 staining. Lung adenocarcinomas commonly metastasize to the bones, liver, and central nervous system but very rarely to the pancreas. There have been only a few reported cases of pancreatic tumors that manifested clinically as a result of primary lung cancer metastases however, even though uncommon, hematogenous spread of cancerous tissue should be considered on the differential as a cause for obstructive jaundice in the setting of lung adenocarcinoma.

Risk Factors and Outcomes of Rapid Correction of Severe Hyponatremia.

BACKGROUND AND OBJECTIVES: Rapid correction of severe hyponatremia can result in serious neurologic complications, including osmotic demyelination. Few data exist on incidence and risk factors of rapid correction or osmotic demyelination. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a retrospective cohort of 1490 patients admitted with serum sodium <120 mEq/L to seven hospitals in the Geisinger Health System from 2001 to 2017, we examined the incidence and risk factors of rapid correction and osmotic demyelination. Rapid correction was defined as serum sodium increase of >8 mEq/L at 24 hours. Osmotic demyelination was determined by manual chart review of all available brain magnetic resonance imaging reports. RESULTS: Mean age was 66 years old (SD=15), 55% were women, and 67% had prior hyponatremia (last outpatient sodium <135 mEq/L). Median change in serum sodium at 24 hours was 6.8 mEq/L (interquartile range, 3.4-10.2), and 606 patients (41%) had rapid correction at 24 hours. Younger age, being a woman, schizophrenia, lower Charlson comorbidity index, lower presentation serum sodium, and urine sodium <30 mEq/L were associated with greater risk of rapid correction. Prior hyponatremia, outpatient aldosterone antagonist use, and treatment at an academic center were associated with lower risk of rapid correction. A total of 295 (20%) patients underwent brain magnetic resonance imaging on or after admission, with nine (0.6%) patients showing radiologic evidence of osmotic demyelination. Eight (0.5%) patients had incident osmotic demyelination, of whom five (63%) had beer potomania, five (63%) had hypokalemia, and seven (88%) had sodium increase >8 mEq/L over a 24-hour period before magnetic resonance imaging. Five patients with osmotic demyelination had apparent neurologic recovery. CONCLUSIONS: Among patients presenting with severe hyponatremia, rapid correction occurred in 41%; nearly all patients with incident osmotic demyelination had a documented episode of rapid correction. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_06_05_CJASNPodcast_18_7_G.mp3.