Does Peritoneal Protein Transport Increase with Peritoneal Dialysis Therapy Duration and Lead to Extracellular Water Overload in Peritoneal Dialysis Patients?

Faster peritoneal transport status has been associated with adverse outcomes for peritoneal dialysis (PD) patients. Peritoneal protein clearance, through large pores, may be a surrogate marker of local inflammation. We wished to determine whether peritoneal protein transport increased with PD duration or was associated with extracellular water (ECW) expansion. We studied the relationships between 4 h Dialysate (D)/Serum (S) protein and ECW excess, using multifrequency bioelectrical impedance assessments, in 103 PD patients with up to 4 years of prospectively collected peritoneal equilibrium test (PET) results. 4 h PET D/S total protein and creatinine ratios were stable over time (K‐W test, P = 0.063 and P = 0.3357, respectively). The initial PET 4 h D/S creatinine and D/S total protein correlated with ECW excess (r = 0.33, P = 0.003, and r = 0.27, P = 0.019, respectively), but thereafter there was no association. CRP and albumin did not correlate with 4 h D/S creatinine or total protein. Serial 4 h D/S total protein and 4 h D/S creatinine correlated all time points (P < 0.001). At the start of PD therapy, over‐hydration (ECW excess) was observed with higher 4 h D/S creatinine and 4 h D/S total protein ratios, suggesting initial exposure to PD fluids causes faster transport. Thereafter changes in peritoneal creatinine and total protein transport mirrored each other suggesting that similar factors lead to changes in both small and large pore transport, and there was no sustained increase in larger pore transport with therapy time.     

Recurrent urinary tract infection in girls. Group with lower tract findings and a benign course

A group of girls is described with recurrent urinary tract infections characterized by predominantly lower tract symptoms. Clinical, laboratory, and radiography findings during the period of follow-up are presented. Infection persisted in most patients over several years. Response to medical and surgical treatment was unsatisfactory. The mean interval between the initial and most recent radiological study was 6 1/2 years. No case of renal parenchymal scarring was seen.     

Successful biventricular cardiac resynchronization therapy in a failing Fontan patient: Implications of ventriculo‐ventricular interdependency in single ventricle physiology

We describe a Fontan patient with severe heart failure who was successfully treated with biventricular cardiac resynchronization therapy (CRT). Our case shows that strain imaging might play a crucial role in guiding placement of pacing leads and in characterizing the electromechanical substrate associated with a favorable CRT response. Furthermore, we demonstrate for the first time that ventriculo‐ventricular interdependency seems an important mechanical concept, which can be utilized to augment cardiac performance in failing Fontan patients with a functional hypoplastic ventricle.     

Arterial wall thickness and the risk of recurrent ischemic events in carriers of the prothrombin G20210A mutation with clinical manifestations of atherosclerosis

The G20210A mutation in the prothrombin gene is an established risk factor for venous thrombosis. There is controversy about the role of this mutation in arterial thrombotic disease and atherosclerosis. We determined the presence of the prothrombin mutation and examined its influence on carotid and femoral artery intima-media thickness (IMT) and the occurrence of new ischemic events during follow-up in 277 patients with clinically manifest atherosclerotic disease: ischemic stroke, myocardial infarction or peripheral arterial disease. The mean age at entry was 63 years. Mean IMT was significantly higher in carriers of the prothrombin mutation (1.17 (SD 0.29) mm versus 0.97 (SD 0.25) mm: (delta)IMT=0.20, P=0.02). The increase in IMT was not attributable to differences in age, type of arterial disease or cardiovascular risk factors between carriers and non-carriers. During a mean follow-up of 3.5 years, a strong trend for more ischemic events was observed: 4 of the 11 carriers suffered from a recurrent ischemic event, compared with 30 of the 164 male non-carriers (36 versus 18%; P=0.06). These results suggest that the G20210A mutation contributes to the process of arterial wall thickening and is associated with the occurrence of ischemic events in a cohort of elderly persons with established atherosclerosis.     

Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

Objective

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years.

Methods

Detailed clinical data on different parameters describing the disease activity in sequential time periods covering the first 2 years after diagnosis were retrieved from the charts of 311 patients with JIA and compared between subtypes. In a cohort of 146 patients, the relation of these different clinical variables to the course of disease in the following 3 years was evaluated.

Results

The percentage of time with active disease in the first 2 years differed significantly between subtypes. In all subtypes, a broad spectrum of activity was observed. The time with active disease in the first 2 years was the most significant factor associated with the duration of active disease in the following years.

Conclusion

Different percentages of time with active disease have been observed between JIA subtypes in the first 2 years. The cumulative duration of activity varied widely within each subtype. Regarding the prognosis of the individual patient, the clinical course in the first 2 years appears to be predictive of the clinical course in the following years. Patients that have less time with active disease in the first 2 years are not likely to develop an unremitting clinical course later on.     

The use of contrast echocardiography for the detection of cardiac shunts.

Recently, debate has erupted about the clinical significance of cardiovascular shunts. Several major health problems such as stroke and migraine have been associated with patent foramen ovale (PFO) with right-to-left shunt (RLS). The nature of the relationship between these syndromes and PFO is not clearly understood. Technical advances have led to more therapeutic options including device closure of PFO, hence prevention of such a PFO-related stroke has become feasible. Therefore, optimal diagnosis of PFO has become of greater clinical importance. Contrast echocardiography with non-transpulmonary contrast agents has been the cornerstone in diagnosis of PFO with RLS for over four decades. Despite being a relatively invasive procedure, transesophageal echocardiography (TEE) is considered the gold standard for detection of RLS. Several other echocardiographic techniques such as transthoracic echocardiography (TTE) with second harmonic imaging and transcranial Doppler ultrasonography (TCD) have shown increased sensitivity and specificity compared to TEE for the detection of PFO with RLS. Moreover, improvement of skills and techniques used for detection of these shunts has led to greater detection of small and large sized RLS in the echocardiographic laboratory. This review gives and overview of the echocardiographic techniques, contrast agents and manoeuvres used for detection of the major cardiovascular shunts and their clinical relevance to major health problems.     

Combinatorial detection of autoreactive CD8<Superscript>+</Superscript> T cells with HLA-A2 multimers: a multi-centre study by the Immunology of Diabetes Society T Cell Workshop

Aims/hypothesis

Validated biomarkers are needed to monitor the effects of immune intervention in individuals with type 1 diabetes. Despite their importance, few options exist for monitoring antigen-specific T cells. Previous reports described a combinatorial approach that enables the simultaneous detection and quantification of multiple islet-specific CD8⁺ T cell populations. Here, we set out to evaluate the performance of a combinatorial HLA-A2 multimer assay in a multi-centre setting.

Methods

The combinatorial HLA-A2 multimer assay was applied in five participating centres using centralised reagents and blinded replicate samples. In preliminary experiments, samples from healthy donors were analysed using recall antigen multimers. In subsequent experiments, samples from healthy donors and individuals with type 1 diabetes were analysed using beta cell antigen and recall antigen multimers.

Results

The combinatorial assay was successfully implemented in each participating centre, with CVs between replicate samples that indicated good reproducibility for viral epitopes (mean %CV = 33.8). For beta cell epitopes, the assay was very effective in a single-centre setting (mean %CV = 18.4), but showed sixfold greater variability across multi-centre replicates (mean %CV = 119). In general, beta cell antigen-specific CD8⁺ T cells were detected more commonly in individuals with type 1 diabetes than in healthy donors. Furthermore, CD8⁺ T cells recognising HLA-A2-restricted insulin and glutamate decarboxylase epitopes were found to occur at higher frequencies in individuals with type 1 diabetes than in healthy donors.

Conclusions/interpretation

Our results suggest that, although combinatorial multimer assays are challenging, they can be implemented in multiple laboratories, providing relevant T cell frequency measurements. Assay reproducibility was notably higher in the single-centre setting, suggesting that biomarker analysis of clinical trial samples would be most successful when assays are performed in a single laboratory. Technical improvements, including further standardisation of cytometry platforms, will likely be necessary to reduce assay variability in the multi-centre setting.