Urine biomarkers for monitoring juvenile lupus nephritis: a prospective longitudinal study

Background

In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting.

Methods

Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity.

Results

JSLE patients (n?=?64; median age 14.1 years) were seen at 3 (interquartile range: 2–5) clinical reviews over 364 (182–532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p?<?0.001) for active renal disease at the time of the current review. uMCP1 was an excellent predictor of improved renal disease over time (AUC: 0.81; p?=?0.013). uNGAL was a good predictor of worsened renal disease activity (AUC 0.76; p?=?0.04) over time.

Conclusion

Biomarkers (uMCP1, serum C3) can indicate current renal involvement in JSLE, whilst uMCP1 and uNGAL are able to predict subsequent renal disease activity changes. Moving towards biomarker-led monitoring may improve the renal outcome for our patients.     

Prevalence and predictors of cardiac hypertrophy and dysfunction in patients with Type 2 diabetes

The aim of the present study was to determine the prevalence and predictors of an abnormal echocardiogram in patients with Type 2 diabetes. Cardiac function and structure were rigorously assessed by comprehensive transthoracic echocardiographic techniques in 229 patients with Type 2 diabetes. Cardiovascular risk factors and diabetic complications were assessed, and predictors of an abnormal echocardiogram were identified using multivariate logistic regression analysis. An abnormal echocardiogram was present in 166 patients (72%). LVH (left ventricular hypertrophy) occurred in 116 patients (51%), and cardiac dysfunction was found in 146 patients (64%), of whom 109 had diastolic dysfunction alone and 37 had systolic+/-diastolic dysfunction. Independent predictors of an abnormal echocardiogram were obesity, age, the number of antihypertensive drugs used (all P<0.001) and creatinine clearance (P<0.05). The risk of an abnormal echocardiogram increased by 9% for each year over 50 years of age {OR (odds ratio), 1.09 [95% CI (confidence interval), 1.04-1.15]}, 3-fold if obesity was present [BMI (body mass index) >30; OR, 4.2 (95% CI, 1.9-9.0)] and by 80% for each antihypertensive agent used [OR, 1.8 (95% CI, 1.3-2.4) per agent]. In conclusion, an abnormal cardiac echocardiogram is common in patients with Type 2 diabetes. Importantly, although cardiac abnormalities can be predicted by traditional risk factors, such as age, obesity and renal function, the absence of micro- or macro-vascular complications does not predict a normal echocardiogram. We suggest that an echocardiogram identifies those with Type 2 diabetes at increased cardiovascular risk due to occult LVH and diastolic dysfunction, and this information may lead to more aggressive management of known risk factors in the clinic.     

The impact of lactate-buffered high-volume hemofiltration on acid-base balance

OBJECTIVE: To evaluate the effect of high-volume hemofiltration (HVHF) with lactate-buffered replacement fluids on acid-base balance. DESIGN: Randomized crossover study. SETTING: Intensive Care Unit of Tertiary Medical Center PARTICIPANTS: Ten patients with septic shock and acute renal failure. INTERVENTIONS: Random allocation to 8 h of isovolemic high-volume hemofiltration (ultrafiltration rate: 6 l/h) or 8 h of isovolemic continuous venovenous hemofiltration (ultrafiltration rate: 1 l/h) with lactate-buffered replacement fluid with subsequent crossover. MEASUREMENTS AND RESULTS: We measured blood gases, electrolytes, albumin, and lactate concentrations and completed quantitative biophysical analysis of acid-base balance changes. Before high-volume hemofiltration, patients had a slight metabolic alkalosis [pH: 7.42; base excess (BE) 2.4 mEq/l] despite hyperlactatemia (lactate: 2.51 mmol/l). After 2 h of high-volume hemofiltration, the mean lactate concentration increased to 7.30 mmol/l ( p=0.0001). However, a decrease in chloride, strong ion difference effective, and strong ion gap (SIG) compensated for the effect of iatrogenic hyperlactatemia so that the pH only decreased to 7.39 ( p=0.05) and the BE to -0.15 ( p=0.001). After 6 h, despite persistent hyperlactatemia (7 mmol/l), the pH had returned to 7.42 and the BE to 2.45 mEq/l. These changes remained essentially stable at 8 h. Similar but less intense changes occurred during continuous venovenous hemofiltration. CONCLUSIONS: HVHF with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia. However, such hyperlactatemia only has a mild and transient acidifying effect. A decrease in chloride and strong ion difference effective and the removal of unmeasured anions all rapidly compensate for this effect.     

Research methodologies to investigate the experience of breastfeeding: a discussion paper

This paper is a discussion of the importance of choosing appropriate methodologies to research the breastfeeding experience of women in the United Kingdom. Despite a plethora of research emphasising the benefits of breastfeeding to maternal and infant health, there is a relative dearth of research from the United Kingdom about women's experiences of breastfeeding. In order to understand the inherent complexities of successfully promoting and supporting breastfeeding, a mothers’ breastfeeding experience must be examined within her specific context. This is increasingly recognised as a vital tool in providing effective support by health care professionals in extending breastfeeding duration. As such, this highlights the importance that appropriate methodologies are chosen through which to explore this phenomenon from the perspective of those experiencing it. This paper debates the importance of philosophical lines of enquiry in relation to breastfeeding research, and argues that engaging with ontological perspectives would offer opportunities for researchers to engage with women's understanding of breastfeeding in today's society. A hermeneutic phenomenological approach that is informed from feminist methodologies is deemed the most appropriate in researching mothers’ views of breastfeeding.     

High-frequency oscillatory ventilation in adults: clinical considerations and management priorities

Recently, there has been renewed interest in high-frequency oscillatory ventilation (HFOV) as a lung-protective strategy in adults. It limits overdistension and prevents cyclic collapse by maintaining end-expiratory lung volume. Studies have shown that HFOV is safely tolerated in the adult population and may offer more benefit if applied early in the course of disease. These findings have implications for clinicians as the use of HFOV may increase in the coming decade. Gas transport mechanisms, ventilator settings, patient monitoring, and clinical considerations for HFOV are substantially different from conventional mechanical ventilation. This article reviews management strategies and monitoring priorities currently recommended for management of adults receiving HFOV.     

Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women

A range of studies have shown that the complex process of implantation and an establishment of a pregnancy also involves immune factors. Disturbances in these underlying immune mechanisms might lead to implantation and pregnancy failure and may be involved in the pathogenesis of unexplained infertility. Several studies have reported that imbalances in uterine NK (uNK) cell abundance are associated with infertility; however, controversies exist. An increased amount of CD56⁺ uNK cells along with a decrease in CD16⁺ uNK cells have been associated with normal fertility in some studies. Very few studies of FoxP3⁺ regulatory T cells (Tregs) in the pre-implantation endometrium have been performed. Results are sparse and controversial, studies reporting both increased and decreased numbers of Tregs, respectively, in women suffering from infertility. In conclusion, studies imply that uNK cells, Tregs and HLA-G carry pivotal roles regarding the establishment of a healthy pregnancy, and that abnormal immune mechanisms involving these parameters may be associated with infertility. However, more research in early phases of the reproductive cycle, such as investigating the conditions in the endometrium before implantation, is needed to further clarify the underlying mechanisms.     

DSP30 and interleukin‐2 as a mitotic stimulant in B‐cell disorders including those with a low disease burden

Chromosome abnormalities detected during cytogenetic investigations for B‐cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B‐cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B‐cell malignancies. Here, we describe the comparison of two B‐cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B‐cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B‐cell disorders, revealing abnormal cytogenetic results in a range of B‐cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B‐cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B‐cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease.     

A novel ECEL1 mutation expands the phenotype of distal arthrogryposis multiplex congenita type 5D to include pretibial vertical skin creases

Arthrogryposis multiplex congenita (AMC) is a heterogeneous disorder characterized by multiple joint contractures often in association with other congenital abnormalities. Pretibial linear vertical creases are a rare finding associated with arthrogryposis, and the etiology of the specific condition is unknown. We aimed to genetically and clinically characterize a boy from a consanguineous family, presenting with AMC and pretibial vertical linear creases on the shins. Whole exome sequencing and variant analysis revealed homozygous novel missense variants of ECEL1 (c.1163T > C, p.Leu388Pro, NM_004826) and MUSK (c.2572C > T, p.Arg858Cys, NM_005592). Both variants are predicted to have deleterious effects on the protein function, with amino acid positions highly conserved among species. The variants segregated in the family, with healthy mother, father, and sister being heterozygous carriers and the index patient being homozygous for both mutations. We report on a unique patient with a novel ECEL1 homozygous mutation, expanding the phenotypic spectrum of Distal AMC Type 5D to include vertical linear skin creases. The homozygous mutation in MUSK is of unknown clinical significance. MUSK mutations have previously shown to cause congenital myasthenic syndrome, a neuromuscular disorder with defects in the neuromuscular junction.