His bundle pacing guided by automated intrinsic morphology matching is feasible in patients with narrow QRS complexes

Pace mapping and visual comparison of the local pacing response with the intrinsic QRS morphology form the mainstay of His bundle pacing (HBP). We evaluated the performance of a surface lead morphology match algorithm for automated classification of the pacing response in patients with narrow intrinsic QRS undergoing electroanatomic mapping (EAM)-guided HBP. HBP was attempted in 43 patients. In 28 cases with narrow QRS, the EnSite AutoMap Module was used for automated assessment of the QRS morphology resulting from pace mapping in the His cloud area with either a diagnostic catheter or the His lead. An intrinsic morphology match score (IMS) was calculated for 1.546 QRS complexes and assessed regarding its accuracy and performance in classifying the individual pacing response as either selective HBP (S-HBP), nonselective HBP (NS-HBP) or right ventricular stimulation. Automated morphology comparison of 354 intrinsic beats with the individual reference determined a test accuracy of 99% (95% CI 98.96–99.04) and a precision of 97.99–99.5%. For His-lead stimulation, an IMS ≥ 89% identified S-HBP with a sensitivity, specificity and positive predictive value of 1.00 (0.99, 1.00) and a negative predictive value of 0.99 (0.98, 1.00). An IMS between 78 and < 89% indicated NS-HBP with a sensitivity and specificity of 1.00 (0.99, 1.00) and 0.99 (0.98, 1.00), respectively. IMS represents a new automated measure for standardized individual morphology classification in patients with normal QRS undergoing EAM-guided HBP. Clinical trial registration: NCT04416958

Global snow mass measurements and the effect of stratigraphic detail on inversion of microwave brightness temperatures

Snow provides large seasonal storage of freshwater, and information about the distribution of snow mass as Snow Water Equivalent (SWE) is important for hydrological planning and detecting climate change impacts. Large regional disagreements remain between estimates from reanalyses, remote sensing and modelling. Assimilating passive microwave information improves SWE estimates in many regions but the assimilation must account for how microwave scattering depends on snow stratigraphy. Physical snow models can estimate snow stratigraphy, but users must consider the computational expense of model complexity versus acceptable errors. Using data from the National Aeronautics and Space Administration Cold Land Processes Experiment (NASA CLPX) and the Helsinki University of Technology (HUT) microwave emission model of layered snowpacks, it is shown that simulations of the brightness temperature difference between 19 GHz and 37 GHz vertically polarised microwaves are consistent with Advanced Microwave Scanning Radiometer-Earth Observing System (AMSR-E) and Special Sensor Microwave Imager (SSM/I) retrievals once known stratigraphic information is used. Simulated brightness temperature differences for an individual snow profile depend on the provided stratigraphic detail. Relative to a profile defined at the 10 cm resolution of density and temperature measurements, the error introduced by simplification to a single layer of average properties increases approximately linearly with snow mass. If this brightness temperature error is converted into SWE using a traditional retrieval method then it is equivalent to ±13 mm SWE (7% of total) at a depth of 100 cm. This error is reduced to ±5.6 mm SWE (3 % of total) for a two-layer model

Differences of patients’ perceptions for elective diagnostic coronary angiography and percutaneous coronary intervention in stable coronary artery disease between elderly and younger patients

Harald Rittger,1 Barbara Frosch,1 Laura Vitali-Serdoz,1 Matthias Waliszewski2,3 1Medizinische Klinik 1, Klinikum Fürth, Fürth, Germany; 2Medical Scientific Affairs, B. Braun Melsungen AG, Berlin, Germany; 3Department of Internal Medicine and Cardiology, Charité – Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany Aims: There is limited evidence of the differences in expectations between elderly (≥80 years) and younger patients (<80 years) regarding treatment success of percutaneous coronary interventions (PCI). We conducted a survey in patients undergoing diagnostic coronary angiography (DA) and/or intervention (PCI) to identify differences in patient perceptions between elderly and younger patients.Methods and results: This is an all-comers study of consecutive patients who underwent DA and/or PCI. Patients were asked to fill out a questionnaire prior to DA/PCI. This questionnaire consisted of ten questions with potential patient expectations based on an increasing scale of importance from 0 to 5 which were related to the procedure (eg, extend life, decrease symptoms etc.) and the value of “hard” cardiac endpoints like death, stroke, acute myocardial infarction and target lesion revascularization for the patient. Among 200 patients (mean age 76.6±9.3 years, 60.5% male, ejection fraction 63.7%±13.2%), 100 patients (50%) were ≥80 years. For these elderly patients the questions “to remain independent,” “to maintain mobility, so that I can maintain my current life,” and “to prevent myocardial infarction” were rated highest. Regarding “hard” cardiac endpoints “to avoid PCI in the future” was rated lowest in younger and in elderly patients. Significant differences were found between the age groups with the items “to avoid myocardial infarction,” “avoid heart insufficiency,” “to extend my life” and “to maintain mobility so that I can maintain my current life” (P<0.001).Conclusions: In our survey we found significant differences in patient expectations between elderly and younger patients regarding the outcome of DA/PCI. Keywords: patient perceptions, coronary angiography, percutaneous coronary intervention, elderl

Tumor Necrosis Factor-α (TNF-α) regulates shedding of TNF-α receptor 1 by the metalloprotease-disintegrin ADAM8: evidence for a protease-regulated feedback loop in neuroprotection

Tumor necrosis factor α (TNF-α) is a potent cytokine in neurodegenerative disorders, but its precise role in particular brain disorders is ambiguous. In motor neuron (MN) disease of the mouse, exemplified by the model wobbler (WR), TNF-α causes upregulation of the metalloprotease-disintegrin ADAM8 (A8) in affected brain regions, spinal cord, and brainstem. The functional role of A8 during MN degeneration in the wobbler CNS was investigated by crossing WR with A8-deficient mice: a severely aggravated neuropathology was observed for A8-deficient WR compared with WR A8+/− mice, judged by drastically reduced survival [7 vs 81% survival at postnatal day 50 (P50)], accelerated force loss in the forelimbs, and terminal akinesis. In vitro protease assays using soluble A8 indicated specific cleavage of a TNF-α receptor 1 (p55 TNF-R1) but not a TNF-R2 peptide. Cleavage of TNF-R1 was confirmed in situ, because levels of soluble TNF-R1 were increased in spinal cords of standard WR compared with wild-type mice but not in A8-deficient WR mice. In isolated primary neurons and microglia, TNF-α-induced TNF-R1 shedding was dependent on the A8 gene dosage. Furthermore, exogenous TNF-α showed higher toxicity for cultured neurons from A8-deficient than for those from wild-type mice, demonstrating that TNF-R1 shedding by A8 is neuroprotective. Our results indicate an essential role for ADAM8 in modulating TNF-α signaling in CNS diseases: a feedback loop integrating TNF-α, ADAM8, and TNF-R1 shedding as a plausible mechanism for TNF-α mediated neuroprotection in situ and a rationale for therapeutic intervention

DDMC-p53 gene therapy with or without cisplatin and microwave ablation

Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2 Joshua Stopek,3 Thomas Vogl,4 Frank Hübner,1 J Francis Turner,5,6 Robert Browning,7 Konstantinos Zarogoulidis,2 Antonis Drevelegas,8 Konstantinos Drevelegas,8 Kaid Darwiche,9 Lutz Freitag,9 Harald Rittger101II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany; 2Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Covidien, Jersey City, NJ, USA; 4Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 5Division of Interventional Pulmonology, 6Medical Oncology, Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, 7Pulmonary and Critical Care Medicine, Interventional Pulmonology, National Naval Medical Center, Walter Reed Army Medical Center, Bethesda, MD, USA; 8Radiology Department, Interbalkan European Medical Center, Thessaloniki, Greece; 9Department of interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Essen-Duisburg, Essen, Germany; 10Medical Clinic I, ‘Fuerth Hospital, University of Erlangen, Erlangen, GermanyAbstract: Lung cancer remains the leading cause of death in cancer patients. Severe treatment side effects and late stage of disease at diagnosis continue to be an issue. We investigated whether local treatment using 2-diethylaminoethyl-dextran methyl methacrylate copolymer with p53 (DDMC-p53) with or without cisplatin and/or microwave ablation enhances disease control in BALBC mice. We used a Lewis lung carcinoma cell line to inoculate 140 BALBC mice, which were divided into the following seven groups; control, cisplatin, microwave ablation, DDMC-p53, DDMC-p53 plus cisplatin, DDMC-p53 plus microwave, and DDMC-p53 plus cisplatin plus microwave. Microwave ablation energy was administered at 20 W for 10 minutes. Cisplatin was administered as 1 mL/mg and the DDMC-p53 complex delivered was 0.5 mL. Increased toxicity was observed in the group receiving DDMC-p53 plus cisplatin plus microwave followed by the group receiving DDMC-p53 plus cisplatin. Infection after repeated treatment administration was a major issue. We conclude that a combination of gene therapy using DDMC-p53 with or without cisplatin and microwave is an alternative method for local disease control. However, more experiments are required in a larger model to identify the appropriate dosage profile.Keywords: DDMC, p53, carboplatin, microwave, non-small cell lung cance

Drug eluting stents for malignant airway obstruction: A critical review of the literature

Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement. © Ivyspring International Publisher