Efficacy and mortality of rotating sheaths versus laser sheaths for transvenous lead extraction: a meta-analysis.

BACKGROUND: Rotating and laser sheaths are both routinely used in transvenous lead extraction (TLE) which can lead to catastrophic complications including death. The efficacy and risk of each approach are uncertain. To perform a meta-analysis to compare success and mortality rates associated with rotating and laser sheaths. METHODS: We searched electronic academic databases for case series of consecutive patients and randomized controlled trials published 1998-2017 describing the use of rotating and laser sheaths for TLE. Among 48 studies identified, rotating sheaths included 1,094 patients with 1,955 leads in 14 studies, and laser sheaths included 7,775 patients with 12,339 leads in 34 studies. Patients receiving rotating sheaths were older (63 versus 60 years old) and were more often male (74% versus 72%); CRT-P/Ds were more commonly extracted using rotating sheaths (12% versus 7%), whereas ICDs were less common (37% versus 42%), p > 0.05 for all. Infection as an indication for lead extraction was higher in the rotating sheath group (59.8% versus 52.9%, p = 0.002). The mean time from initial lead implantation was 7.2 years for rotating sheaths and 6.3 years for laser sheaths (p > 0.05). RESULTS: Success rates for complete removal of transvenous leads were 95.1% in rotating sheaths and 93.4% in laser sheaths (p < 0.05). There was one death among 1,094 patients (0.09%) in rotating sheaths and 66 deaths among 7,775 patients (0.85%) in laser sheaths, translating to a 9.3-fold higher risk of death with laser sheaths (95% CI 1.3 to 66.9, p = 0.01). CONCLUSIONS: Laser sheaths were associated with lower complete lead removal rate and a 9.3-fold higher risk of death.

US hospital webpages on atrial fibrillation ablation: A potential source for misinformation.

INTRODUCTION: Atrial fibrillation (AF) ablation is performed worldwide. To attract patients, hospitals frequently have webpages that tout the success of the procedure. The information disseminated to the public via these webpages has not been systematically reviewed. Our objective was to assess accuracy of information delivered to the public on hospital websites in regard to atrial AF ablation. METHODS: From July 2019 to January 2020, we performed a Google search for all US hospitals registered with Medicare to see if they had a webpage describing AF ablation. Resulting hospital webpages were abstracted for data on AF ablation success rates and risks. Success rates over 86%, the highest success rate in the medical literature, were deemed exaggerated. RESULTS: Among 4805 hospitals, 487 had webpages describing AF ablation and 33 discussed success rates of AF ablation. Twelve percentage reported exaggerated success rates, 3% referred to ablation as a cure, and 2.8% referred to ablation as a tool to eliminate AF. Less than 10% of webpages describing AF ablation noted the potential need for a second ablation to achieve the stated success rate and merely 16% mentioned risks of the procedure. One percentage of webpages directly suggested AF ablation could reduce risk of stroke while others indirectly suggested it by discussing cessation of anticoagulation. Two webpages mentioned reduced mortality. CONCLUSION: US hospital webpages rarely discuss AF ablation. When discussed, there were concerning unsubstantiated claims regarding mortality, stroke prevention, and need for medical therapy. This could lead to some patients undergoing AF ablation based on faulty understanding.

Feasibility of Coronary Artery Calcium Scoring on Dual-Energy Chest Computed Tomography: A Prospective Comparison with Electrocardiogram-Gated Calcium Score Computed Tomography.

Rationale and Objectives: This study aimed to evaluate the feasibility of assessment using the coronary artery calcium score (CACS) in dual-energy chest computed tomography (CT). Materials and Methods: We prospectively enrolled 30 patients (19 male, 11 female; mean age, 63.73 ± 9.40 years) who clinically required contrast-enhanced chest CT. The patients underwent electrocardiogram-gated cardiac calcium-scoring CT with a slice thickness of 2.5 mm followed by a sequentially non-gated contrast-enhanced dual-energy chest CT using 140/80 fast kVp switching technology with slice thicknesses of 1.25 mm and 2.5 mm. Virtual unenhanced (VUE) images were then reconstructed from the dual-energy CT using the material suppressed iodine (MSI) technique. Results: The mean heart rates were 63.33 ± 12.01 beats per minute. The mean CACS on the coronary calcium-scoring CT was 361.1 ± 435.5, and CACSs of the VUE images were 76.8 ± 128.6 (2.5 mm slice) and 108.7 ± 165.1 (1.25 mm slice). The correlation coefficients of CACS between the coronary calcium-scoring CT with the VUE 2.5 mm and 1.25 mm images were 0.888 and 0.904, respectively. The inter-observer agreements for the calcium score measurement between the calcium-scoring CT, VUE 2.5 mm, and VUE 1.25 mm were 1.000, 0.999, and 1.000, respectively. Conclusions: In conclusion, assessment of CACS using dual-energy chest CT might be feasible when using MSI virtual unenhanced dual-energy chest CT images with a slice thickness of 1.25 mm.

Safety of transvenous lead removal in adult congenital heart disease: a national perspective.

INTRODUCTION AND OBJECTIVES: Data are scarce on outcomes of transvenous lead removal (TLR) in adult congenital heart disease (CHD). We evaluated the safety of the TLR procedure in adult CHD patients from a 10-year national database. METHODS: We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify TLR procedures in adult patients with and without CHD from 2005 to 2014. Outcomes included in-hospital mortality and complications. RESULTS: Of 132 068 adult patients undergoing TLR, 1939 had simple CHD, 657 had complex CHD, and 626 had unclassified CHD. The number of TLR procedures in adult CHD slightly increased from 236 in 2005 to 445 in 2014, with fluctuations over the study period. The overall rate of any complications in the TLR procedure was 16.6% in patients with CHD vs 10.1% in patients without CHD (P <.001). In a propensity score-matched cohort, CHD was associated with a higher risk of any complication after full adjustment vs patients without CHD (adjusted odd ratio, 1.49; 95% confidence interval, 1.11-1.99; P=.007). Simple and complex CHD were associated with 1.5- and 2.1-fold increased risks of any TLR-related complication, respectively. CHD was not associated with an increased risk of in-hospital mortality (adjusted odd ratio, 0.77; 95% confidence interval, 0.42-1.39; P=.386). CONCLUSIONS: Compared with patients without CHD, adult patients with simple and complex CHD undergoing TLR are more likely to have complications but show no increase in mortality.

Pure red cell aplasia and seronegative myasthenia gravis in association with thymoma.

Pure red cell aplasia is an uncommon paraneoplastic syndrome of thymoma. Myasthenia gravis is the most common paraneoplastic syndrome associated with thymoma. We present a case of a 79-year-old Pacific Islander female who presented with profound fatigue, generalized weakness, significant unintentional weight loss, bilateral ptosis, and anemia. The bone marrow biopsy showed near absence of erythroid elements consistent with pure red cell aplasia. Ice-pack test was consistent with myasthenia gravis and computed tomography of the chest demonstrated a thymoma. The patient was started on immunosuppressive treatment with prednisone and cyclosporine. This case demonstrates a rare combination of paraneoplastic manifestations of thymoma: pure red cell aplasia and myasthenia gravis.

Eruptive xanthoma associated with severe hypertriglyceridemia and poorly controlled type 1 diabetes mellitus.

Eruptive xanthoma is characterized by yellowish skin papules encircled by an erythematous halo and associated with severe hypertriglyceridemia above 2,000 mg/dl. Hypertriglyceridemia can be caused by primary genetic mutations, secondary causes, such as uncontrolled diabetes, obesity, alcohol overuse, or combinations of both. Eruptive xanthoma can serve as an important clinical indicator of underlying systemic conditions (e.g. hypertriglyceridemia and uncontrolled diabetes mellitus). It is important for clinicians to recognize it to prevent further complications such as pancreatitis and cardiovascular disease.

Reported mortality with rotating sheaths vs. laser sheaths for transvenous lead extraction.

AIMS: Rotating sheaths and laser sheaths are commonly used for transvenous lead extraction. This study aims to compare observed mortality between both approaches. METHODS AND RESULTS: The Manufacturer and User Facility Device Experience database was searched from 2011 to 2016 to determine number of deaths associated with each sheath. An independent analytics firm provided estimates for number of cases done, allowing calculation of market share. A sensitivity analysis was performed to determine relative risk (RR) of mortality at the calculated market share (36% rotating/64% laser) and two others. Additional sensitivity analyses assumed underreporting of deaths associated with rotating sheaths. An estimated 50 545 extractions were performed. Thirteen deaths were associated with rotating sheaths compared to 167 with laser sheaths. Of these, 92% (rotating) and 95% (laser) were due to cardiovascular injury. At the calculated market share, the RR of death was 7.2 times greater with laser sheaths [95% confidence interval (CI) 4.1-12.7, P < 0.0001]. At market share estimates of 25% rotating/75% laser and 45% rotating/55% laser, the RR of death with laser sheaths was 4.3 (95% CI 2.4-7.5, P < 0.0001) and 10.5 times greater (95% CI 6.0-18.5, P < 0.0001), respectively. The RR of death remained significant when assuming deaths with rotating sheaths were underreported and when deaths using both sheaths were attributed to the rotating sheath. CONCLUSIONS: Lead extraction with laser sheaths appears to be associated with a higher risk of mortality compared to rotating sheaths. Further studies are warranted to confirm this finding.

Safety of Transvenous Lead Removal in Patients ≥70 Years of Age in the United States from 2005 to 2012.

Cardiac devices are increasingly an element of treatment for the elderly, leading to more frequent transvenous lead removal (TLR) procedures in this population. Data on TLR in very elderly patients, especially nonagenarians, is scarce. We used Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify a total of 36,099 patients ≥70 years who underwent TLR from 2005 to 2012, with outcomes including in-hospital mortality and complications. The in-hospital mortality rate was significantly higher in nonagenarians without device infection (0.9% in age 70 to 79 vs 0.7% in age 80 to 89 vs 2.6% in age ≥90, p = 0.012), but overall complication rates were not different in age groups regardless of infection status and co-morbidity index (all p >0.05). Among patients with device infection, octogenarians, and nonagenarians were not associated with increased risk of in-hospital mortality relative to septuagenarians after controlling for all other confounders. However, in patients without device infection, logistic regression showed significantly higher mortality in patients age ≥90 years (odd ratio 4.22, 95% confidence interval 1.66 to 10.75, p = 0.003), but not in patients age 80 to 89 years (odd ratio 1.05, 95% confidence interval 0.48 to 2.30, p = 0.907), compared with patients age 70 to 79 years. In conclusion, in nonagenarians with infection, mortality is driven more by the patient's other conditions than by age. For patients without infection, however, nonagenarians experienced higher mortality than younger patients.

Stress-driven structural and functional switching of Ypt1p from a GTPase to a molecular chaperone mediates thermo tolerance in Saccharomyces cerevisiae.

Guanosine triphosphatases (GTPases) function as molecular switches in signal transduction pathways that enable cells to respond to extracellular stimuli. Saccharomyces cerevisiae yeast protein two 1 protein (Ypt1p) is a monomeric small GTPase that is essential for endoplasmic reticulum-to-Golgi trafficking. By size-exclusion chromatography, SDS-PAGE, and native PAGE, followed by immunoblot analysis with an anti-Ypt1p antibody, we found that Ypt1p structurally changed from low-molecular-weight (LMW) forms to high-molecular-weight (HMW) complexes after heat shock. Based on our results, Ypt1p exhibited dual functions both as a GTPase and a molecular chaperone, and furthermore, heat shock induced a functional switch from that of a GTPase to a molecular chaperone driven by the structural change from LMW to HMW forms. Subsequently, we found, by using a galactose-inducible expression system, that conditional overexpression of YPT1 in yeast cells enhanced the thermotolerance of cells by increasing the survival rate at 55°C by ∼60%, compared with the control cells expressing YPT1 in the wild-type level. Altogether, our results suggest that Ypt1p is involved in the cellular protection process under heat stress conditions. Also, these findings provide new insight into the in vivo roles of small GTP-binding proteins and have an impact on research and the investigation of human diseases.

Preparation and properties of hollow fiber membranes for removing virus and bacteria.

In this study, polysulfone hollow fiber membrane was successfully prepared by phase inversion method for separation of virus and bacteria. When we prepare the hollow fiber membrane, we controlled various factors such as the polymer concentration, air gap and internal coagulation to investigate effect to membrane property. Morphology of surface and cross section of membrane were measured by field emission scanning electron microscope (FE-SEM). Water flux of membrane was measured using test modules. Mean pore diameter of membrane was calculated using rejection of polystyrene (PS) latex beads for separation of virus and bacteria. Flux and mean flow pore diameter of prepared membrane show 800 L/mh, 0.03 µm at 1.0 kgf/cm2. The bacteria removal performance of prepared UF membranes was over 6 logs

Impact of Oncotype DX on treatment decisions in ER-positive, node-negative breast cancer with histologic correlation.

Oncotype DX, a gene-expression profiling assay, provides stratification of patients with estrogen-receptor positive, lymph-node-negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen-receptor positive, node-negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen-receptor positive, lymph-node-negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.

Thioredoxin reductase type C (NTRC) orchestrates enhanced thermotolerance to Arabidopsis by its redox-dependent holdase chaperone function.

Genevestigator analysis has indicated heat shock induction of transcripts for NADPH-thioredoxin reductase, type C (NTRC) in the light. Here we show overexpression of NTRC in Arabidopsis (NTRC°(E)) resulting in enhanced tolerance to heat shock, whereas NTRC knockout mutant plants (ntrc1) exhibit a temperature sensitive phenotype. To investigate the underlying mechanism of this phenotype, we analyzed the protein's biochemical properties and protein structure. NTRC assembles into homopolymeric structures of varying complexity with functions as a disulfide reductase, a foldase chaperone, and as a holdase chaperone. The multiple functions of NTRC are closely correlated with protein structure. Complexes of higher molecular weight (HMW) showed stronger activity as a holdase chaperone, while low molecular weight (LMW) species exhibited weaker holdase chaperone activity but stronger disulfide reductase and foldase chaperone activities. Heat shock converted LMW proteins into HMW complexes. Mutations of the two active site Cys residues of NTRC into Ser (C217/454S-NTRC) led to a complete inactivation of its disulfide reductase and foldase chaperone functions, but conferred only a slight decrease in its holdase chaperone function. The overexpression of the mutated C217/454S-NTRC provided Arabidopsis with a similar degree of thermotolerance compared with that of NTRC°(E) plants. However, after prolonged incubation under heat shock, NTRC°(E) plants tolerated the stress to a higher degree than C217/454S-NTRC°(E) plants. The results suggest that the heat shock-mediated holdase chaperone function of NTRC is responsible for the increased thermotolerance of Arabidopsis and the activity is significantly supported by NADPH.

Inhibitor of apoptosis (IAP)-like protein lacks a baculovirus IAP repeat (BIR) domain and attenuates cell death in plant and animal systems.

A novel Arabidopsis thaliana inhibitor of apoptosis was identified by sequence homology to other known inhibitor of apoptosis (IAP) proteins. Arabidopsis IAP-like protein (AtILP) contained a C-terminal RING finger domain but lacked a baculovirus IAP repeat (BIR) domain, which is essential for anti-apoptotic activity in other IAP family members. The expression of AtILP in HeLa cells conferred resistance against tumor necrosis factor (TNF)-α/ActD-induced apoptosis through the inactivation of caspase activity. In contrast to the C-terminal RING domain of AtILP, which did not inhibit the activity of caspase-3, the N-terminal region, despite displaying no homology to known BIR domains, potently inhibited the activity of caspase-3 in vitro and blocked TNF-α/ActD-induced apoptosis. The anti-apoptotic activity of the AtILP N-terminal domain observed in plants was reproduced in an animal system. Transgenic Arabidopsis lines overexpressing AtILP exhibited anti-apoptotic activity when challenged with the fungal toxin fumonisin B1, an agent that induces apoptosis-like cell death in plants. In AtIPL transgenic plants, suppression of cell death was accompanied by inhibition of caspase activation and DNA fragmentation. Overexpression of AtILP also attenuated effector protein-induced cell death and increased the growth of an avirulent bacterial pathogen. The current results demonstrated the existence of a novel plant IAP-like protein that prevents caspase activation in Arabidopsis and showed that a plant anti-apoptosis gene functions similarly in plant and animal systems.

Heat-induced chaperone activity of serine/threonine protein phosphatase 5 enhances thermotolerance in Arabidopsis thaliana.

• This study reports that Arabidopsis thaliana protein serine/threonine phosphatase 5 (AtPP5) plays a pivotal role in heat stress resistance. A high-molecular-weight (HMW) form of AtPP5 was isolated from heat-treated A. thaliana suspension cells. AtPP5 performs multiple functions, acting as a protein phosphatase, foldase chaperone, and holdase chaperone. The enzymatic activities of this versatile protein are closely associated with its oligomeric status, ranging from low oligomeric protein species to HMW complexes. • The phosphatase and foldase chaperone functions of AtPP5 are associated primarily with the low-molecular-weight (LMW) form, whereas the HMW form exhibits holdase chaperone activity. Transgenic over-expression of AtPP5 conferred enhanced heat shock resistance to wild-type A. thaliana and a T-DNA insertion knock-out mutant was defective in acquired thermotolerance. A recombinant phosphatase mutant (H290N) showed markedly increased holdase chaperone activity. • In addition, enhanced thermotolerance was observed in transgenic plants over-expressing H290N, which suggests that the holdase chaperone activity of AtPP5 is primarily responsible for AtPP5-mediated thermotolerance. • Collectively, the results from this study provide the first evidence that AtPP5 performs multiple enzymatic activities that are mediated by conformational changes induced by heat-shock stress.

Heat-shock and redox-dependent functional switching of an h-type Arabidopsis thioredoxin from a disulfide reductase to a molecular chaperone.

A large number of thioredoxins (Trxs), small redox proteins, have been identified from all living organisms. However, many of the physiological roles played by these proteins remain to be elucidated. We isolated a high M(r) (HMW) form of h-type Trx from the heat-treated cytosolic extracts of Arabidopsis (Arabidopsis thaliana) suspension cells and designated it as AtTrx-h3. Using bacterially expressed recombinant AtTrx-h3, we find that it forms various protein structures ranging from low and oligomeric protein species to HMW complexes. And the AtTrx-h3 performs dual functions, acting as a disulfide reductase and as a molecular chaperone, which are closely associated with its molecular structures. The disulfide reductase function is observed predominantly in the low M(r) forms, whereas the chaperone function predominates in the HMW complexes. The multimeric structures of AtTrx-h3 are regulated not only by heat shock but also by redox status. Two active cysteine residues in AtTrx-h3 are required for disulfide reductase activity, but not for chaperone function. AtTrx-h3 confers enhanced heat-shock tolerance in Arabidopsis, primarily through its chaperone function.

Heat-shock dependent oligomeric status alters the function of a plant-specific thioredoxin-like protein, AtTDX.

We found that Arabidopsis AtTDX, a heat-stable and plant-specific thioredoxin (Trx)-like protein, exhibits multiple functions, acting as a disulfide reductase, foldase chaperone, and holdase chaperone. The activity of AtTDX, which contains 3 tetratricopeptide repeat (TPR) domains and a Trx motif, depends on its oligomeric status. The disulfide reductase and foldase chaperone functions predominate when AtTDX occurs in the low molecular weight (LMW) form, whereas the holdase chaperone function predominates in the high molecular weight (HMW) complexes. Because deletion of the TPR domains results in a significant enhancement of AtTDX disulfide reductase activity and complete loss of the holdase chaperone function, our data suggest that the TPR domains of AtTDX block the active site of Trx and play a critical role in promoting the holdase chaperone function. The oligomerization status of AtTDX is reversibly regulated by heat shock, which causes a transition from LMW to HMW complexes with concomitant functional switching from a disulfide reductase and foldase chaperone to a holdase chaperone. Overexpression of AtTDX in Arabidopsis conferred enhanced heat shock resistance to plants, primarily via its holdase chaperone activity.