Utility of immunohistochemistry with C3d in C3 glomerulopathy.

C3-dominance by immunofluorescence is a defining feature in the diagnosis of C3 glomerulopathy. Most pathologists stain for C3c, which has been reported as a trace/negative even in otherwise clear-cut cases of dense deposit disease. We investigated the usefulness of C3d immunohistochemistry in biopsies with C3 glomerulopathy as an ancillary diagnostic tool. All biopsies from patients diagnosed with C3 glomerulopathy in the period January 2005 to June 2017 in the Erasmus MC, Rotterdam were included (n = 14; 10 C3 glomerulonephritis, 4 dense deposit disease). The staining pattern of C3d and C4d by immunohistochemistry was analyzed. As controls, biopsies from patients with immune complex membranoproliferative glomerulonephritis (n = 2), infection-associated glomerulonephritis (n = 6), pauci-immune crescentic glomerulonephritis (n = 7), tubulointerstitial nephritis (n = 7) and chronic-active antibody-mediated rejection (n = 9) were included. All 14 biopsies with C3 glomerulopathy showed a C3d score of ≥2, including two clear-cut biopsies with C3 glomerulopathy originally showing a trace/negative staining for C3c. In the control group, a C3d score ≥2 was observed in 11 biopsies (35%; 2 with immune complex membranoproliferative glomerulonephritis (100%), 6 with infection-associated glomerulonephritis (100%), 1 with pauci-immune crescentic glomerulonephritis (14%), 1 with tubulointerstitial nephritis (14%) and 1 with chronic-active antibody-mediated rejection (11%)). C4d was positive in 71% of the biopsies with C3 glomerulopathy (10/14). In conclusion, C3d immunohistochemistry is a valuable tool in the diagnosis of C3 glomerulopathy, especially in cases in which C3c immunofluorescence shows a trace/negative. We recommend the use of C3d in addition to C3c in cases suspicious for C3 glomerulopathy.

Physicians' clinical prediction of survival in head and neck cancer patients in the palliative phase.

BACKGROUND: The prognosis of patients with incurable head and neck cancer (HNC) is a relevant topic. The mean survival of these patients is 5 months but may vary from weeks to more than 3 years. Discussing the prognosis early in the disease trajectory enables patients to make well-considered end-of-life choices, and contributes to a better quality of life and death. However, physicians often are reluctant to discuss prognosis, partly because of the concern to be inaccurate. This study investigated the accuracy of physicians' clinical prediction of survival of palliative HNC patients. METHODS: This study was part of a prospective cohort study in a tertiary cancer center. Patients with incurable HNC diagnosed between 2008 and 2011 (n = 191), and their treating physician were included. Analyses were conducted between July 2018 and February 2019. Patients' survival was clinically predicted by their physician ≤3 weeks after disclosure of the palliative diagnosis. The clinical prediction of survival in weeks (CPS) was based on physicians' clinical assessment of the patient during the outpatient visits. More than 25% difference between the actual survival (AS) and the CPS was regarded as a prediction error. In addition, when the difference between the AS and CPS was 2 weeks or less, this was always considered as correct. RESULTS: In 59% (n = 112) of cases survival was overestimated. These patients lived shorter than predicted by their physician (median AS 6 weeks, median CPS 20 weeks). In 18% (n = 35) of the cases survival was correctly predicted. The remaining 23% was underestimated (median AS 35 weeks, median CPS 20 weeks). Besides the differences in AS and CPS, no other significant differences were found between the three groups. There was worse accuracy when predicting survival closer to death: out of the 66 patients who survived 6 weeks or shorter, survival was correctly predicted in only eight (12%). CONCLUSION: Physicians tend to overestimate the survival of palliative HNC patients. This optimism can result in suboptimal use of palliative and end-of-life care. The future development of a prognostic model that provides more accurate estimates, could help physicians with personalized prognostic counseling.

Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated. METHODS AND ANALYSIS: This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05499949.