Lead dependent tricuspid dysfunction: Analysis of the mechanism and management in patients referred for transvenous lead extraction

Background: Lead-dependent tricuspid dysfunction (LDTD) is one of important complicationsin patients with cardiac implantable electronic devices. However, this phenomenon isprobably underestimated because of an improper interpretation of its clinical symptoms. Theaim of this study was to identify LDTD mechanisms and management in patients referred fortransvenous lead extraction (TLE) due to lead-dependent complications.Methods: Data of 940 patients undergoing TLE in a single center from 2009 to 2011 wereassessed and 24 patients with LDTD were identifi ed. The general indications for TLE, pacingsystem types and lead dwell time in both study groups were comparatively analyzed. Theradiological and clinical effi cacy of TLE procedure was also assessed in both groups with precisionestimation of clinical status patients with LDTD (before and after TLE). Additionally,mechanisms, concomitant lead-dependent complications and degree (severity) of LDTD beforeand after the procedure were evaluated. Telephone follow-up of LDTD patients was performedat the mean time 1.5 years after TLE/replacement procedure.Results: The main indications for TLE in both groups were similar (apart from isolatedLDTD in 45.83% patients from group I). Patients with LDTD had more complex pacing systemswith more leads (2.04 in the LDTD group vs. 1.69 in the control group; p = 0.04). Therewere more unnecessary loops of lead in LDTD patients than in the control group (41.7% vs.5.24%; p = 0.001). There were no signifi cant differences in average time from implantationto extraction and the number of preceding procedures. Signifi cant tricuspid regurgitation(TR-grade III–IV) was found in 96% of LDTD patients, whereas stenosis with regurgitationin 4%. The 10% frequency of severe TR (not lead dependent) in the control group patients wasobserved. The main mechanism of LDTD was abnormal leafl et coaptation caused by: loop ofthe lead (42%), septal leafl et pulled toward the interventricular septum (37%) or too intensivelead impingement of the leafl ets (21%). LDTD patients were treated with TLE and reimplantationof the lead to the right ventricle (87.5%) or to the cardiac vein (4.2%), or surgery procedure with epicardial lead placement following ineffective TLE (8.3%). The radiological and clinicaleffi cacy of TLE procedure was very high and comparable between the groups I and II (91.7%vs. 94.2%; p = 0.6 and 100% vs. 98.4%; p = 0.46, respectively). Repeated echocardiographyshowed reduced severity of tricuspid valve dysfunction in 62.5% of LDTD patients. The follow--up interview confi rmed clinical improvement in 75% of patients (further improvement aftercardiosurgery in 2 patients was observed).Conclusions: LDTD is a diagnostic and therapeutic challenge. The main reason for LDTDwas abnormal leafl et coaptation caused by lead loop presence, or propping, or impingementthe leafl ets by the lead. Probably, TLE with lead reimplantation is a safe and effective optionin LDTD management. An alternative option is TLE with omitted tricuspid valve reimplantation.Cardiac surgery with epicardial lead placement should be reserved for patients withineffective previous procedures

Characterization of insulin crystalline form in isolated β-cell secretory granules

Insulin is stored in vivo inside the pancreatic β-cell insulin secretory granules. In vitro studies have led to an assumption that high insulin and Zn2+ concentrations inside the pancreatic β-cell insulin secretory granules should promote insulin crystalline state in the form of Zn2+-stabilized hexamers. Electron microscopic images of thin sections of the pancreatic β-cells often show a dense, regular pattern core, suggesting the presence of insulin crystals. However, the structural features of the storage forms of insulin in native preparations of secretory granules are unknown, because of their small size, fragile character and difficult handling. We isolated and investigated the secretory granules from MIN6 cells under near-native conditions, using cryo-electron microscopic (Cryo-EM) techniques. The analysis of these data from multiple intra-granular crystals revealed two different rhomboidal crystal lattices. The minor lattice has unit cell parameters (a ≃ b ≃ 84.0 Å, c ≃ 35.2 Å), similar to in vitro crystallized human 4Zn2+-insulin hexamer, whereas the largely prevalent unit cell has more than double c-axis (a ≃ b ≃ c ≃ 96.5 Å) that probably corresponds to two or three insulin hexamers in the asymmetric unit. Our experimental data show that insulin can be present in pancreatic MIN6 cell granules in a microcrystalline form, probably consisting of 4Zn2+-hexamers of this hormone

The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn 2+ levels : Zn 2+ levels in β-cells

Insulin is produced and stored inside the pancreatic β-cell secretory granules, where it is assumed to form Zn 2+ -stabilized oligomers. However, the actual storage forms of this hormone and the impact of zinc ions on insulin production in vivo are not known. Our initial X-ray fluorescence experiment on granules from native Langerhans islets and insulinoma-derived INS-1E cells revealed a considerable difference in the zinc content. This led our further investigation to evaluate the impact of the intra-granular Zn 2+ levels on the production and storage of insulin in different model β-cells. Here, we systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA (mRNA) and total insulin analysis. These studies revealed an impaired insulin production in the permanent β-cell lines with the diminished intracellular zinc content. The drop in insulin and Zn 2+ levels was paralleled by a lower expression of ZnT8 zinc transporter mRNA and hampered proinsulin processing/folding in both permanent cell lines. To summarize, we showed that the disruption of zinc homeostasis in the model β-cells correlated with their impaired insulin and ZnT8 production. This indicates a need for in-depth fundamental research about the role of zinc in insulin production and storage

Wytyczne Polskiego Towarzystwa Gastroenterologii dotyczące nadzoru kolonoskopowego po polipektomii — adaptacja wytycznych europejskich

Zasady nadzoru kolonoskopowego po polipektomii zawarte w prezentowanym artykule opracowano na podstawie europejskich wytycznych dotyczących zapewnienia jakości w badaniach przesiewowych i diagnostyce raka jelita grubego. Zalecenia oparto na istniejących dowodach naukowych i uzupełniono o opinie ekspertów w sprawach niepopartych dowodami, a całość została zaakceptowana przez Zarząd Główny Polskiego Towarzystwa Gastroenterologii. Stwierdzenia, w których istnieją różnice w porównaniu z wytycznymi europejskimi, oznaczono znakiem „#”. Gastroenterologia Kliniczna 2011, tom 3, nr 2, 55–6

Polish Society of Gastroenterology guidelines for colonoscopy surveillance following polypectomy : adapted European guidelines

Zasady nadzoru kolonoskopowego po polipektomii zawarte w prezentowanym artykule opracowano na podstawie europejskich wytycznych dotyczących zapewnienia jakości w badaniach przesiewowych i diagnostyce raka jelita grubego. Zalecenia oparto na istniejących dowodach naukowych i uzupełniono o opinie ekspertów w sprawach niepopartych dowodami, a całość została zaakceptowana przez Zarząd Główny Polskiego Towarzystwa Gastroenterologii. Stwierdzenia, w których istnieją różnice w porównaniu z wytycznymi europejskimi, oznaczono znakiem „#”.The presented guidelines for colonoscopy surveillance after polypectomy are based on recently published European guidelines for quality assurance in colorectal cancer screening and diagnosis. The guidelines are evidence-based and supplemented with experts’ opinion on topics with little evidence; the entire document has been accepted by the Governing Board of the Polish Society of Gastroenterology. Statements that differ from original statements in European guidelines are marked with “#”

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

Carrier Trap Density Reduction at SiO₂/4H-Silicon Carbide Interface with Annealing Processes in Phosphoryl Chloride and Nitride Oxide Atmospheres

The electrical and physical properties of the SiC/SiO2 interfaces are critical for the reliability and performance of SiC-based MOSFETs. Optimizing the oxidation and post-oxidation processes is the most promising method of improving oxide quality, channel mobility, and thus the series resistance of the MOSFET. In this work, we analyze the effects of the POCl3 annealing and NO annealing processes on the electrical properties of metal–oxide–semiconductor (MOS) devices formed on 4H-SiC (0001). It is shown that combined annealing processes can result in both low interface trap density (Dit), which is crucial for oxide application in SiC power electronics, and high dielectric breakdown voltage comparable with those obtained via thermal oxidation in pure O2. Comparative results of non-annealed, NO-annealed, and POCl3-annealed oxide–semiconductor structures are shown. POCl3 annealing reduces the interface state density more effectively than the well-established NO annealing processes. The result of 2 × 1011 cm−2 for the interface trap density was attained for a sequence of the two-step annealing process in POCl3 and next in NO atmospheres. The obtained values Dit are comparable to the best results for the SiO2/4H-SiC structures recognized in the literature, while the dielectric critical field was measured at a level ≥9 MVcm−1 with low leakage currents at high fields. Dielectrics, which were developed in this study, have been used to fabricate the 4H-SiC MOSFET transistors successfully

Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2

Abstract Insulin-like Growth Factor-2 (IGF2) is important for the regulation of human embryonic growth and development, and for adults’ physiology. Incorrect processing of the IGF2 precursor, pro-IGF2(156), leads to the formation of two IGF2 proforms, big-IGF2(87) and big-IGF2(104). Unprocessed and mainly non-glycosylated IGF2 proforms are found at abnormally high levels in certain diseases, but their mode of action is still unclear. Here, we found that pro-IGF2(156) has the lowest ability to form its inactivating complexes with IGF-Binding Proteins and has higher proliferative properties in cells than IGF2 and other IGF prohormones. We also showed that big-IGF2(104) has a seven-fold higher binding affinity for the IGF2 receptor than IGF2, and that pro-IGF2(87) binds and activates specific receptors and stimulates cell growth similarly to the mature IGF2. The properties of these pro-IGF2 forms, especially of pro-IGF2(156) and big-IGF2(104), indicate them as hormones that may be associated with human diseases related to the accumulation of IGF-2 proforms in the circulation