Successful catheter cryoablation of Hisian ectopy using 2 new diagnostic criteria based on unipolar and bipolar recordings of the His electrogram

We describe the case of a 61-year-old woman who underwent successful catheter cryoablation of a symptomatic Hisian ectopy. Diagnosis was based on features of the HV interval assessed from a bipolar recording during mapping. The location of the arrhythmic focus was identified using simultaneous unipolar and bipolar recordings of the His electrogram. This case report highlights the use of 2 new criteria for the diagnosis and mapping of Hisian ectopy, and the successful use of cryothermia for the ablation of extrasystoles arising from the His bundle.     

Nephrectomy for the failed renal allograft in children: predictors and outcomes

Background

There are no guidelines for the removal of a failed renal allograft, and its impact on subsequent dialysis and retransplantation has not yet been described.

Methods

We performed a 10-year review of allograft failure to study the factors that determined an outcome of transplant nephrectomy and choice of subsequent renal replacement therapy in children with or without nephrectomy.

Results

A total of 34 children developed graft failure over the 10-year study period, of whom 18 (53 %) required transplant nephrectomy. The median graft survival was 1.1 (range 0.2–10.6) versus 7.5 (1.5–15.0) years in the nephrectomy and non-nephrectomy groups, respectively (p?=?0.011). Children with graft failure within 1 year of transplantation were four-fold more likely to require transplant nephrectomy than those with graft failure after 1 year (p?=?0.04). Renal biopsy performed at ≤8 weeks prior to graft loss showed Banff grade II acute rejection in 13 of the 18 children who required subsequent nephrectomy versus three of the 13 children who did not need nephrectomy (p?=?0.01). Inflammation (fever, graft tenderness and raised C-reactive protein (CRP) in the 2 weeks preceding graft failure) was seen in 66 % of nephrectomized children, but not in any in the non-nephrectomy group (p?=?0.0003 for CRP between groups). Banff II rejection, an inflammatory response and the time post-transplantation significantly and independently predicted the outcome of nephrectomy (p?=?0.008, R ²?=?67 %). Human leukocyte antigen (HLA) antibody levels after graft failure were higher in the nephrectomy group (p?=?0.0003), but there was no difference between groups in terms of the presence or class of donor-specific antibodies. Of the children with graft failure, 82 % required dialysis (61 % hemodialysis) and 35 % have to date been successfully retransplanted.

Conclusions

Children with Banff II rejection, an inflammatory response and early graft loss are more likely to require transplant nephrectomy. Nephrectomy may be associated with higher circulating HLA antibody levels.     

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53–0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.In the last decades, renal replacement therapy with hemodialysis has become a standard of care for patients with ESRD. Despite continuous improvement, annual mortality among these patients ranges between 15% and 25%.^1,2 Hemodialysis techniques are based on the ability of molecules to diffuse across a semipermeable membrane, which allows adequate clearance of low molecular weight particles. To increase the clearance of middle-to-large molecules, synthetic membranes with high water permeability (high-flux membranes) were introduced years ago. The anticipated benefit of high-flux over low-flux hemodialysis on patient survival was not confirmed in the Hemodialysis (HEMO) study.³ However, the Membrane Permeability Outcome (MPO) study,⁴ as well as a post hoc analysis in diabetic patients, showed that high-flux hemodialysis improved long-term survival in patients with hypoalbuminemia.Clearance of middle-to-large molecules can be increased by combining diffusive and convective transport through hemodiafiltration. The introduction of online hemodiafiltration (OL-HDF) using ultrapure dialysate as the source of the replacement fluid has allowed the convective volume to be increased and has reduced the cost of the procedure.⁵ Randomized studies with limited sample sizes and nonrandomized studies have shown that OL-HDF improves hemodynamic stability and response to erythropoietic-stimulating agents (ESAs) and reduces the incidence of hemodialysis-associated amyloidosis and chronic inflammation.^6–11 The effect of OL-HDF on patient survival is derived from noncontrolled studies. The European Dialysis Outcomes and Practice Pattern Study was associated with a mortality risk reduction of 35% in patients treated with high-efficiency hemodiafiltration compared with those treated with conventional hemodialysis.¹² These results were confirmed in other noncontrolled studies conducted in several European countries,^13–15 although two recent, randomized studies failed to show differences in patient survival^16,17In 2007, the Catalonian Health Authorities approved a specific additional reimbursement for OL-HDF to dialysis care providers and the Catalonian Society of Nephrology promoted this randomized study (On-Line Hemodiafiltration Survival Study, or Estudio de Supervivencia de Hemodiafiltración On-Line [ESHOL]) to compare the effect of OL-HDF over hemodialysis on patient survival.¹⁸     

Abnormal functioning of the semantic network in schizophrenia patients with thought disorganization. An exemplar production task

Numerous studies have indicated that thought disorganization in schizophrenia is associated with an enhanced semantic priming effect. This suggests abnormal functioning of the semantic network in these patients, with disinhibited spreading of semantic activation. We investigated whether thought disorganization is also associated with atypical responses in the production of semantic category exemplars. An exemplar production task was administered to 43 patients with schizophrenia and 24 healthy controls. The names of 16 semantic categories were provided, and the participants were requested to produce an exemplar for each category. The typicality of the response was rated according to norms. Higher ratings of thought disorganization were associated with the production of more atypical exemplars. In addition, the patients with high thought disorganization scores were significantly more atypical in their responses than were the healthy controls. In contrast, the patients with low thought disorganization scores were equivalent to the healthy controls. Higher ratings of affective flattening were associated with the production of less atypical exemplars. The results corroborate, within a different paradigm than semantic priming, the theory that thought disorganization is associated with faster and more distant connections within the semantic network. This effect is counteracted by affective flattening.     

Neurogenesis in temporal lobe epilepsy: Relationship between histological findings and changes in dentate gyrus proliferative properties

Objective

The relationship between hippocampal histopathological abnormalities, epileptogenesis and neurogenesis remains rather unclear.

Methods

Tissue samples including the subgranular zone of dentate gyrus (DG) were freshly collected for tissue culture for neurospheres generation in 16 patients who underwent surgery for drug-resistant temporal lobe epilepsy. Remaining tissues were histologically examined to assess the presence of mesial temporal sclerosis (MTS) and focal cortical dysplasia.

Results

MTS was detected in 8 cases. Neurospheres were formed in 10/16 cases. Only three out of these 10 cases exhibited MTS; on the contrary 5/6 cases lacking neurosphere proliferation presented MTS. There was a significant correlation between presence of MTS and absence of proliferation (p = 0.0389). We also observed a correlation between history of febrile seizures (FS) and presence of MTS (p = 0.0004) and among the 6 cases lacking neurosphere proliferation, 4 cases (66.6%) had experienced prolonged FS. Among “proliferating” cases the percentage of granular cells pathology (GCP) was lower (20% vs 50%) compared to “non proliferating” cases.

Conclusion

A decreased potential to generate neurosphere from the SGZ is related to MTS and to alterations of dentate gyrus granule cells, especially in MTS type 1b and GCP type 1. These histological findings may have different prognostic implications, regarding seizure and neuropsychological outcome, compared to patients with other epileptogenic lesions (such as FCD, glioneuronal tumours, vascular lesions).     

A comparative study of glial and non‐neural cell properties for transplant‐mediated repair of the injured spinal cord

Cell transplantation is one strategy for encouraging regeneration after spinal cord injury and a range of cell types have been investigated for their repair potential. However, variations in study design complicate determination of which cells are most effective. In this study we have carried out a direct comparison of the regenerative and integrative properties of several cell preparations following transplantation into the lesioned rat spinal cord. Transplants included: (i) purified olfactory ensheathing cells (OECs) and (ii) fibroblast‐like cells, from olfactory bulb (OBFB‐L), (iii) a 50:50 mixture of (i) and (ii) (OEC/OBFB‐L), (iv) dissociated nasal mucosa (OM), (v) purified peripheral nerve Schwann cells (SCs), (vi) peripheral nerve fibroblasts, and (vii) skin fibroblasts (SF). All transplants supported axonal regeneration: OECs and SCs promoted the greatest regeneration while OBFB‐like cells were least efficient and mixed cell populations were less effective than purified populations. Tract‐tracing experiments demonstrated that none of the cell types promoted regeneration beyond the lesion. Although all cell types prevented cavity formation, the extent of astrocytic hypertrophy [GFAP immunoreactivity (IR) at the transplant/lesion site] differed markedly. OECs and SCs were associated with the least GFAP‐IR, fibroblasts and fibroblast‐like cells resulted in greater GFAP‐IR while hypertrophy surrounding transplants of OM was most extensive. These differences in host‐transplant reactivity were confirmed by transplanting cells into normal spinal cord where the cellular interaction is not complicated by injury. Thus, purified glial cells have advantages for transplant‐mediated repair, combining maximal support for axonal regeneration with a minimal astrocytic reaction around the transplant site. © 2013 Wiley Periodicals, Inc.     

Induction of atypical EAE mediated by transgenic production of IL‐6 in astrocytes in the absence of systemic IL‐6

Interleukin (IL)‐6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL‐6‐deficient mice (IL‐6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte‐targeted production of IL‐6‐restricted to the cerebellum (GFAP‐IL6), EAE induced with MOG_35–55 was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL‐6 produced in the central nervous system, we have generated mice producing IL‐6 essentially only in the brain by crossing the GFAP‐IL6 mice with IL‐6 KO mice. Interestingly, GFAP‐IL6‐IL‐6 KO mice showed a milder but almost identical phenotype as the GFAP‐IL6 mice, which correlated with a lower load of inflammatory cells and decreased microglial reactivity. These results indicate that not only is cerebellar IL‐6 production and eventual leakage into the peripheral compartment the dominating factor controlling this type of EAE but that it can also facilitate induction of autoimmunity in the absence of normal systemic IL‐6 production. © 2013 Wiley Periodicals, Inc.