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Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease., Journal Article, Research Support, Non-U.S. Gov't, FLWOA, SCOPUS: ar.j, info:eu-repo/semantics/published

Background. The clinical course of acute renal failure (ARF) related to crush syndrome is very complex, because of co-existing surgical and/or medical complications. After the devastating Marmara earthquake that struck Turkey in August 1999, 639 patients were identified with nephrological problems, whose clinical findings have been the subject of this analysis. Methods. Specific questionnaires asking about 63 variables were sent to 35 reference hospitals that treated the victims. Clinical findings of the renal victims were analysed. Results. At admission, high fever was noted in 31.8% of the patients; the temperature of non-survivors was higher (P = 0.027). Mean blood pressure was higher in survivors (P = 0.004) and dialysed victims (P < 0.001). Most (61.4%) patients were oligo-anuric; oliguria lasted for 10.8 +/- 7.2 days. Thoracic and abdominal traumas were associated with a higher risk of mortality. 397 fasciotomies and 121 amputations were performed in 790 traumatized extremities. Fasciotomies were associated with sepsis (P < 0.001) and dialysis needs (P < 0.0001), while amputations were associated with mortality (P < 0.0001). Medical complications, which were associated with dialysis needs (P < 0.0001) and mortality (P < 0.0001), were observed in 51.5% of patients. In a multivariate analysis model of medical complications, disseminated intravascular coagulation (DIC) (P < 0.0001, OR = 5.81), and adult respiratory distress syndrome (ARDS) (P = 0.0001, OR = 4.53) were predictors of mortality. Conclusions. In the aftermath of catastrophic earthquakes, clinical findings of the renal victims can predict the final outcome. While fasciotomies indicate dialysis needs, extremity amputations, abdominal and thoracic traumas are associated with higher rates of mortality in addition to DIC and ARDS.

Background: We compared three access flow (AF) monitoring techniques: blood dilution using ultrasound (US), blood temperature monitoring (BTM), and online clearance monitoring (OCM), and investigated the impact of dialyzer blood flow (QB), measurement time point and patient’s position. Methods: US, BTM and OCM were performed in 20 hemodialysis (HD) patients at QB300. OCM was unreliable for measuring AF and was therefore further omitted. US and BTM measurements were repeated in 10 patients at QB200 ml/min, in 15 patients at the first weekly HD start and end and at the midweek HD start, and switching position during midweek HD. Results: AFs of 1,104 ± 607 (US) and 1,264 ± 664 ml/min (BTM) significantly correlated. No differences were found comparing AF at QB300 and QB200. AF decreased from HD start to end, while no difference was found changing patient’s position. Conclusion: AFs by BTM and US correlated well and may be measured at QB200–300 in all measured positions.

Background/Aims: Vascular access thrombosis is one of the most morbid problems encountered by hemodialysis patients. Surveillance protocols utilizing venous pressure (Vp) and vascular access blood flow (VABF) measurements have been employed to preserve vascular access. We undertook a study to evaluate combined dynamic Vp and VABF measurements in the identification of vascular access impairment. We also assessed the effect of preventive repair on thrombosis rates in impaired vascular accesses identified by surveillance. Methods: Eighty-six chronic hemodialysis patients with a functioning vascular access were enrolled into the surveillance protocol. All vascular accesses with greater than 50% of monthly Vp readings >120 mm Hg or VABF 25% compared to the highest previously measured value, were considered positive. Stenosis >50% on fistulography or a thrombotic event were defined as a ‘vascular access impairment episode’ while a stenosis Results: The sensitivity and specificity of the combined surveillance protocol for AVFs were 73.3 and 91%, respectively. In AVGs, they were 68.8 and 87.5%, respectively. The rate of thrombotic events was lower in patients who underwent early repair. The addition of dynamic Vp did not reduce the thrombosis rate any further than surveillance based on VABF alone. Conclusion: Combined monitoring for surveillance of AVFs improved sensitivity but had little benefit in AVGs over VABF monitoring alone. Raising VABF cutoff levels might increase and improve identification of vascular access risk for thrombosis, but at the expense of lower specificity.

Cool dialysate and midodrine have been used successfully to treat intradialytic hypotension (IDH) in the end-stage renal disease population. However, the exact mechanisms by which these interventions improve hemodynamic stability are not well known. We undertook a study to evaluate the effect of these modalities on intradialytic hemodynamics in patients with documented dialysis-associated hypotension. We used the ultrasound dilution technique to measure cardiac output (CO), central blood volume (CBV), and peripheral vascular resistance (PVR) in these patients. The study was performed in two phases. Phase 1 consisted of control (1A) and cool dialysate (1B) studies, whereas phase 2 consisted of control (2A) and midodrine (2B) studies. CO, CBV, and PVR were measured 30 minutes after the initiation of hemodialysis (HD) and 30 minutes before the termination of HD using the HD01 monitor. Blood pressure was measured pre-HD and post-HD. Fourteen patients with documented IDH completed the study. CO and CBV were significantly more preserved in the cool dialysate and midodrine phases compared with control phases. PVR increased in all phases of the study. Declines in mean arterial pressures from pre-HD to post-HD were less with cool dialysate versus control and midodrine versus control. Ultrafiltration volumes were not significantly different between phases. Cool dialysate and midodrine appear to improve intradialytic hemodynamics in patients with dialysis-associated hypotension, mainly through the preservation of CBV and CO, rather than significantly elevating PVR.