Serum trace element concentrations in children with chronic renal failure

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N-acetylcysteine does not prevent contrast-induced nephropathy after cardiac catheterization in patients with diabetes mellitus and chronic kidney disease: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) constitute to be a high-risk population for the development of contrast-induced nephropathy (CIN), in which the incidence of CIN is estimated to be as high as 50%. We performed this trial to assess the efficacy of <it>N</it>-acetylcysteine (NAC) in the prevention of this complication.</p> <p>Methods</p> <p>In a prospective, double-blind, placebo controlled, randomized clinical trial, we studied 90 patients undergoing elective diagnostic coronary angiography with DM and CKD (serum creatinine ≥ 1.5 mg/dL for men and ≥ 1.4 mg/dL for women). The patients were randomly assigned to receive either oral NAC (600 mg BID, starting 24 h before the procedure) or placebo, in adjunct to hydration. Serum creatinine was measured prior to and 48 h after coronary angiography. The primary end-point was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.5 mg/dL (44.2 μmol/L) or ≥ 25% above baseline at 48 h after exposure to contrast medium.</p> <p>Results</p> <p>Complete data on the outcomes were available on 87 patients, 45 of whom had received NAC. There were no significant differences between the NAC and placebo groups in baseline characteristics, amount of hydration, or type and volume of contrast used, except in gender (male/female, 20/25 and 34/11, respectively; P = 0.005) and the use of statins (62.2% and 37.8%, respectively; P = 0.034). CIN occurred in 5 out of 45 (11.1%) patients in the NAC group and 6 out of 42 (14.3%) patients in the placebo group (P = 0.656).</p> <p>Conclusion</p> <p>There was no detectable benefit for the prophylactic administration of oral NAC over an aggressive hydration protocol in patients with DM and CKD.</p> <p>Trial registration</p> <p>NCT00808795</p

Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy

Ponatinib for Treating Chronic Myeloid Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig®; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article presents the critical review of the company's submission by the ERG and the outcome of the NICE guidance. Clinical evidence for ponatinib was derived from a phase II, industry-sponsored, single-arm, open-label, multicentre, non-comparative study. Despite the limited evidence and potential for biases, this study demonstrated that ponatinib was likely to be an effective treatment (in terms of major cytogenetic response and major haematological response) with an acceptable safety profile for patients with CML. Given the absence of any head-to-head studies comparing ponatinib with other relevant comparators, the company undertook a matching-adjusted indirect comparison (MAIC) of ponatinib with bosutinib. The approach was only used for patients with CP-CML because comprehensive data were not available for the AP- or BP-CML groups to allow the matching technique to be used. Despite the uncertainty about the MAIC approach, ponatinib was considered likely to offer advantages over bosutinib in the third-line setting, particularly for complete cytogenetic response. The company developed two health economic models to assess the cost effectiveness of ponatinib for the treatment of patients in CP-CML or in advanced CML (AP- or BP-CML, which were modelled separately). The company did not adequately explore the uncertainty in the survivor functions. As a result, the ERG believed the uncertainty in the decision problem was underestimated. Exploratory analyses undertaken by the ERG produced the following results for ponatinib. In CP-CML, from £18,246 to £27,667 per quality-adjusted life-year (QALY) gained compared with best supportive care (BSC), from £19,680 to £37,381 per QALY gained compared with bosutinib and from £18,279 per QALY gained to dominated compared with allogeneic stem cell transplant (allo-SCT). In AP-CML, the cost per QALY gained for ponatinib ranged from £7123 to £17,625 compared with BSC, and from dominating to £61,896 per QALY gained compared with allo-SCT. In BP-CML, the cost effectiveness of ponatinib ranged from £5033 per QALY gained to dominated compared with allo-SCT, although it was likely to be at the more favourable end of this range, and dominant in all scenarios compared with BSC. The NICE appraisal committee concluded that ponatinib is a cost-effective use of NHS resources in the considered population, subject to the company providing the agreed discount in the Patient Access Scheme

Long-term treatment of childhood refractory and steroid dependent nephrotic syndrome with Cyclosporin A

Background: Cyclosporin A (CsA) is now commonly used in the management of children with steroid-dependent and steroid resistant nephoitic syndrome. It has been reported to be effective in maintaining remission in 70-100 percent of patients with SDNS but somewhat SRNS 0-100 percent. The aim of this study was to evaluate the efficacy of long-term (CsA) in children with refractory nephrotic syndrome (RNS) and steroid dependent nephrotic syndrome (SDNS). Materials and Methods: The long-term effect of (CsA) in 91 Iranian children aged 3 months to 11 years (54 with RNS and 37 with SDNS) was assessed between 1984 and 1999. Eighty of 91 children received renal biopsy prior to introduction of (CsA), and the other 11 patients had not consent for kidney biopsy. If the patients did not show remission aftre receiving 3-6 months of (CsA), the medication was discontinued. Results: All patient were treated with (CsA) in combination with low dose alternate day prednisolone. In children with RNS and SDNS, therapy with (CsA) induced, remission in 25 of 54 (46.2 percent) and 27 of 37 (73 percent) respectively (P&lt;0.02). Of the 32 patients with minimal change disease (MCD), 23 (72 percent) responded to therapy, compared with 4 of 18 (22 percent) with focal segmental glomerulosclerosis (FSGS) (P&lt;0.005). Twenty-four (48 percent) of 50 who entered complete remission, had relapse 1-12 months after cessation of (CsA). The duration between the onset of nephrotic syndrome (NS) and administration of (CsA) and sexuality of patients had no effect in result of treatment. Side effects occurred in 25 patients (27.4 percent). No patients exhibited raised transaminases, 8 (8.7 percent) of the children developed hirsutism, 7 (7.6 percent) hypertension, 7 (7.6 percent) gingival hyperplasia, (2.2 percent) neurological toxicity and 1 (1 percent) increase in serum creatinine. Conclusion: Our findings suggest that (CsA) can be used to induce a complete remission in a significant proportion of patients with RNS and SDNS, and patients with SDNS have areasonable potential for remission than children with RNS. Resistant to steroid and cyclophosphamid

"SENSORINEURAL HEARING LOSS IN CHILDREN WITH END-STAGE RENAL DISEASE"

One of the complications of end-stage renal disease (ESRD) is sensorineural hearing loss (SNHL). Despite large number of studies on adults ESRD patients, there are only a few reported surveys regarding SNHL in children. To determine the prevalence of SNHL in children with ESRD and its relationship with sex of patients, presence of hypertension, history of ototoxic drugs administration and duration of dialysis, we evaluated 30 children and adolescents suffering from ESRD who were under hemodialysis therapy with standard pure-tone audiometry. The ages of children were 5-17.5 years (mean 12 years). Patients with Alport’s syndrome and other hereditary or congenital syndromes involving the ears were excluded from the study. SNHL was detected in 9 patients (30%); 3 children had unilateral and 6 had bilateral SNHL (15 ears). In all of these 15 ears SNHL was in high frequencies (4000-8000 Hz). In 10 ears (66%) also there was SNHL in middle frequencies and in 7 ears (46.6%)there was hearing loss in all frequencies (250-8000 Hz). The severity of SNHL was mild in 7, moderate in 9, severe in 13 and profound in 3 ears in at least one frequency. There was no significant relationship between SNHL and sex of patients, presence of hypertension, history of ototoxic drugs administration and duration of dialysis (P values were 0.8107, 0.3217, 0.69, 0.087, respectively). SNHL is common in children and adolescents with ESRD and must be considered in rehabilitation of these children; the etiology of this impairment is not clear