Aptamer-Based Screen of Neuropsychiatric Lupus Cerebrospinal Fluid Reveals Potential Biomarkers That Overlap With the Choroid Plexus Transcriptome.

OBJECTIVE: As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform. METHODS: CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases. RESULTS: Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, α2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins. CONCLUSION: Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential.

Survival and morbidity outcomes after pelvic exenteration for pelvic sarcoma: an institutional series.

BACKGROUND: To describe our institutional experience in the management of locally advanced primary, and recurrent pelvic sarcoma through pelvic exenteration (PE). METHODS: Patients undergoing PE for locally advanced primary or recurrent pelvic sarcoma between 2003 and 2017 were identified from a prospectively maintained database at a single quaternary referral hospital in Sydney, Australia were eligible for review. The primary outcomes measured were surgical resection margin and survival. Secondary outcome measures included 30-day morbidity, in hospital length of stay (LOS) and return to theatre. RESULTS: There were 29 patients who underwent PE for pelvic sarcoma during the study period, with 55% (n = 16) having advanced primary tumours and 45% (n = 13) having recurrent disease. The R0 resection rate was 52% (n = 15); and five-year-survival of 38% (n = 11). The R0 resection was noted to be higher in patients having primary advanced tumours (56%) compared to those with recurrent disease (46%), however this failed to reach statistical significance in this cohort. There was no recorded 30-day mortality. Grade 3 or higher Clavien-Dindo complications were uncommon (14%), but more likely in patients undergoing surgery for recurrent disease (75%). CONCLUSION: In our cohort of patients with locally advanced and recurrent disease, more than 50% achieved an R0 resection. Recurrent disease makes R0 resection more difficult and can lead to higher morbidity, need for 30-day re-intervention and longer in hospital LOS. PE surgery remains the only curative option for locally advanced, and recurrent sarcoma in the pelvis, and can be performed with acceptable survival and morbidity outcomes.

Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen.

In the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn's disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

Open Thrombectomy for Acute Abdominal Aortic Occlusion Due to Tumor Embolism after Lung Resection.

Arterial tumor embolization is a rare but often catastrophic complication of lung resection for malignancy. This case describes tumor embolization to the abdominal aorta in a patient with metastatic sarcoma. After partial pneumonectomy he developed acute kidney injury, bilateral lower limb ischemia and spinal cord ischemia. Computed tomography angiogram demonstrated complete occlusion of the paravisceral aorta. Perfusion was restored with open thromboembolectomies of the abdominal aorta, superior mesenteric artery and bilateral lower limbs. For perioperative lung cancer patients with acute arterial occlusion intraluminal tumor should be considered and thereby an open approach to revascularisation adopted.