Conclusion: Our robust customized GSA seems to be a promising first-line rapid screening tool for PIDs at an affordable price, which opens opportunities for low-cost genetic testing in developing countries. The technique is scalable, allows numerous new genetic variants to be added, and offers the potential for genetic testing not only in PIDs, but also in many other genetic diseases.

Background: Since the late '90s, infliximab (Remicade ®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima ® were introduced in clinical practice. Aim: To investigate the interchangeability of Remicade ® (originator infliximab) and its biosimilar Remsima ® in patients with rare immune-mediated inflammatory diseases (IMIDs). Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade ® to Remsima ® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation. Results: Forty eight patients treated with Remicade ® were switched to Remsima ® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima ® treatment, one withdrew from the study and one received additional corticosteroid therapy. Xue et al. Recurrent Disease Activity on Remsima ® Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade ® to Remsima ®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade ® to Remsima ®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires wellconsidered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening.

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Background: Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has also been implicated in the pathogenesis of ADPKD in pre-clinical models, but human data are limited. Here, we hypothesized that urinary PGE2 excretion is associated with impaired osmoregulation, disease severity and disease progression in patients with ADPKD. Methods: Urinary excretions of PGE2 and its metabolite (PGEM) were measured in a prospective cohort of patients with ADPKD. Linear regression was used for the cross-sectional analysis of the associations between urinary PGE2 and PGEM excretions, markers of osmoregulation and disease severity. Cox regression and linear mixed models were used for the longitudinal analysis of the associations between urinary PGE2 and PGEM excretions and disease progression. In two separate intervention studies we quantified the effect of starting tolvaptan and adding hydrochlorothiazide to tolvaptan on urinary PGE2 and PGEM excretions. Results: In 562 patients with ADPKD (61% female, eGFR 63 ± 28 ml/min/1.73 m2) higher urinary PGE2 or PGEM excretions were independently associated with higher plasma copeptin, lower urine osmolality, lower eGFR and greater total kidney volume. Patients with higher baseline urinary PGE2 and PGEM excretions had an increased risk of 40% eGFR loss or kidney failure (HR 1.28 and 1.47 for each doubling in urinary PGE2 or PGEM excretions) and a faster change in eGFR over time (-0.39 and -0.53 ml/min/1.73 m2/year for each doubling in urinary PGE2 or PGEM excretions). In the intervention studies, inducing polyuria by tolvaptan significantly increased urinary PGEM excretion, while reducing polyuria by adding hydrochlorothiazide to tolvaptan significantly increased urinary PGE2 excretion. Conclusions: Higher urinary PGE2 and PGEM excretions in patients with ADPKD are associated with parameters of osmoregulation, disease severity and progression.