Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study

IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.     

Acute sensorineural hearing loss in hemodialysis patients

Abstract

Background: Approximately, 30–40% of patients experienced hearing loss under regular hemodialysis.

Objective: This study reviewed our experience on treating acute hearing loss in patients under regular hemodialysis over the past two decades.

Methods: Twenty-six patients having acute hearing loss under hemodialysis were divided into two groups based on their etiologies. Sixteen patients (16 ears) with sudden sensorineural hearing loss (SSHL) were assigned to Group A and 10 patients (13 ears) with endolymphatic hydrops (EH) were assigned to Group B.

Results: No significant difference was noted between Groups A and B, regardless of hemodialysis duration, clinical manifestation, underlying systemic diseases, blood examination, and vestibular test battery. In contrast, serum osmolality was significantly lower in Group B (292?±?11 mOsm/kg) than in Group A (310?±?11 mOsm/kg). Furthermore, Group B (40?±?14?dB) had better mean hearing level than Group A (87?±?21?dB) in the initial audiogram, and a higher hearing improvement rate (69%) than Group A (19%).

Conclusions and significance: Both SSHL and EH are major causes for precipitating acute hearing loss in hemodialysis patients. Compared to SSHL, the less deteriorated MHL and lower serum osmolality in EH provide two clues for differentiating acute hearing loss in hemodialysis patients.     

Fathers of children with autism spectrum disorder: Their perceptions of paternal role a predictor of caregiving satisfaction,self-efficacy and burden

BackgroundThe positive effect of a father’s involvement in children’s upbringing is now recognised. However, research on fathers raising children with autism spectrum disorder (ASD) are still few. This study examines the relationship between the perception, fathers of children with ASD have of the importance of their role in the development of their children and the feelings (self-efficacy, caregiving burden, satisfaction) they express about their parenting experience.MethodSixty-three Swiss Italian fathers of children with ASD completed The Role of the Father Questionnaire (ROFQ), three sub-scales of the Caregiver Survey, a subtest of the Child Adjustment and Parent Efficacy Scale and a home-made questionnaire measuring Perceived Social Support.ResultsThe results from hierarchical multiple regression analyses show that the importance that fathers attach to the paternal role predicts positively their caregiving satisfaction and their feeling of self-efficacy. The children’s challenging behaviours predict positively the caregiving burden whereas the assessment of social support predicts it negatively.ConclusionsThe perception of the importance of the paternal role needs to be considered in the support offered to families with a child with ASD. A better understanding of the fathers’ feelings could be of value for the programmes.     

Sex Disparities in Risk of Mortality Among Children With ESRD

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Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

Background

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.