Elevated fibrosis burden as assessed by MRI predicts cryoballoon ablation failure.

INTRODUCTION: Late-gadolinium enhancement magnetic resonance (LGE-MRI) imaging is increasingly used in management of atrial fibrillation (AFib) patients. Here, we assess the usefulness of LGE-MRI-based fibrosis quantification to predict arrhythmia recurrence in patients undergoing cryoballoon ablation. Our secondary goal was to compare two widely used fibrosis quantification methods. METHODS: In 102 AF patients undergoing LGE-MRI and cryoballoon ablation (mean age 62 years; 64% male; 59% paroxysmal AFib), atrial fibrosis was quantified using the pixel intensity histogram (PIH) and image intensity ratio (IIR) methods. PIH segmentations were completed by a third-party provider as part of the standard of care at our hospital; Image intensity ratio (IIR) segmentations of the same scans were carried out in our lab using a commercially available software package. Fibrosis burdens and spatial distributions for the two methods were compared. Patients were followed prospectively for recurrent arrhythmia following ablation. RESULTS: Average PIH fibrosis was 15.6 ± 5.8% of the left atrial (LA) volume. Depending on threshold (IIRthr ), the average IIR fibrosis (% of LA wall surface area) ranged from 5.0 ± 7.2% (IIRthr = 1.2) to 37.4 ± 10.9% (IIRthr = 0.97). An IIRthr of 1.03 demonstrated the greatest agreement between the methods, but spatial overlap of fibrotic areas delineated by the two methods was modest (Sorenson Dice coefficient: 0.49). Fourty-two patients (41.2%) had recurrent arrhythmia. PIH fibrosis successfully predicted recurrence (HR 1.07; p = .02) over a follow-up period of 362 ± 149 days; regardless of IIRthr , IIR fibrosis did not predict recurrence. CONCLUSIONS: PIH-based volumetric assessment of atrial fibrosis was modestly predictive of arrhythmia recurrence following cryoballoon ablation in this cohort. IIR-based fibrosis was not predictive of recurrence for any of the IIRthr values tested, and the overlap in designated areas of fibrosis between the PIH and IIR methods was modest. Caution must therefore be exercised when interpreting LA fibrosis from LGE-MRI, since the values and spatial pattern are methodology-dependent.

Sustainable fabrication of hybrid silver-copper nanocomposites (Ag-CuO NCs) using Ocimum americanum L. as an effective regime against antibacterial, anticancer, photocatalytic dye degradation and microalgae toxicity.

In this study, a sustainable fabrication of hybrid silver-copper oxide nanocomposites (Ag-CuO NCs) was accomplished utilizing Ocimum americanum L. by one pot green chemistry method. The multifarious biological and environmental applications of the green fabricated Ag-CuO NCs were evaluated through their antibacterial, anticancer, dye degradation, and microalgae growth inhibition activities. The morphological features of the surface functionalized hybrid Ag-CuO NCs were confirmed by FE-SEM and HR-TEM techniques. The surface plasmon resonance λmax peak appeared at 441.56 nm. The average hydrodynamic size distribution of synthesized nanocomposite was 69.80 nm. Zeta potential analysis of Ag-CuO NCs confirmed its remarkable stability at -21.5 mV. XRD and XPS techniques validated the crystalline structure and electron binding affinity of NCs, respectively. The Ag-CuO NCs demonstrated excellent inhibitory activity against Vibrio cholerae (19.93 ± 0.29 mm) at 100 µg/mL. Anticancer efficacy of Ag-CuO NCs was investigated against the A549 lung cancer cell line, and Ag-CuO NCs exhibited outstanding antiproliferative activity with a low IC50 of 2.8 ± 0.05 µg/mL. Furthermore, staining and comet assays substantiated that the Ag-CuO NCs hindered the progression of the A549 cells and induced apoptosis as a result of cell cycle arrest at the G0/G1 phase. Concerning the environmental applications, the Ag-CuO NCs displayed efficient photocatalytic activity against eosin yellow degradation up to 80.94% under sunlight irradiation. Microalgae can be used as an early bio-indicator/prediction of environmental contaminants and toxic substances. The treatment of the Ag-CuO NCs on the growth of marine microalgae Tetraselmis suecica demonstrated the dose and time-dependent growth reduction and variations in the chlorophyll content. Therefore, the efficient multifunctional properties of hybrid Ag-CuO NCs could be exploited as a regime against infective diseases and cancer. Further, the findings of our investigation witness the remarkable scope and potency of Ag-CuO NCs for environmental applications.

Evaluation of Phytochemical Screening, Pigment Content, In Vitro Antioxidant, Antibacterial Potential and GC-MS Metabolite Profiling of Green Seaweed Caulerpa racemosa.

Exploration of seaweeds to unravel their bioactive metabolites from the perspective of wider applications gained substantial importance. The present study was performed to investigate the total phenolic, flavonoid, tannin content, antioxidant activity and antibacterial potential of various solvent extracts of green seaweed Caulerpa racemosa. The methanolic extract showed higher phenolic (11.99 ± 0.48 mg gallic acid equivalents/g), tannin (18.59 ± 0.54 mg tannic acid equivalents/g) and flavonoid (33.17 ± 0.76 mg quercetin equivalents/g) content than other extracts. Antioxidant activity was determined by using 2,2-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay with different concentrations of C. racemosa extracts. The methanolic extract showed higher scavenging potential in both the DPPH and ABTS activity with the inhibition value of 54.21 ± 1.39% and 76.62 ± 1.08%, respectively. Bioactive profiling was also identified by using Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared (FT-IR) techniques. These studies revealed the presence of valuable bioactive compounds in C. racemosa extracts and these compounds might be responsible for antimicrobial, antioxidant, anticancer and anti-mutagenic properties. Major compounds identified in GC-MS were 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, 3-hexadecene and Phthalic acid. In terms of antibacterial activity, C. racemosa has promising antibacterial potential against aquatic pathogens Aeromonas hydrophila, Aeromonas veronii and Aeromonas salmonicida. Further evaluation studies focusing aquatic related aspects would reveal the novel bioproperties and applications of C. racemosa.

Potentials of Aloe barbadensis inclusion in fish feeds on resilience to Aeromonas hydrophila infection in freshwater fish Labeo rohita.

Aquatic bacterial pathogens can cause severe economic loss in aquaculture industry. An opportunistic pathogen, Aeromonas hydrophila is responsible for Motile Aeromonas Septicemia, leading to high mortality rates in fish. The present study was focused on the efficacy of Aloe barbadensis replacing fishmeal diets on hematological, serum biochemical, antioxidant, histopathological parameters, and disease resistance against A. hydrophila infection in Labeo rohita. Isonitrogenous fishmeal replaced diets (FMR) were prepared with varying levels of A. barbadensis at D1 (0%) (control), D2 (25%), D3 (50%), D4 (75%) and D5 (100%) then fed to L. rohita. After 60 days of post-feeding, the experimental fish were challenged with A. hydrophila. Blood and organs were collected and examined at 1- and 15-days post infection (dpi). The results demonstrated that on 1 dpi, white blood cells (WBC), total protein, cholesterol and low-density lipoprotein (LDL) levels were significantly increased in D3 diet fed groups. The D2 and D3 diet fed group showed decreasing trends of serum glutamic pyruvic transaminase (SGPT) and antioxidant enzymes activity on 15 dpi. The histopathological architecture results clearly illustrated that the D3 diet fed group had given a higher protective effect by reducing the pathological changes associated with A. hydrophila infection in liver, intestine and muscle. Higher percentage of survival rate was also observed in D3 diet fed group. Therefore, the present study suggested that the dietary administration of A. barbadensis up to 50% fishmeal replacement (D3 diet) can elicit earlier antioxidant activity, innate immune response and improve survival rate in L. rohita against A. hydrophila infection.

A wearable cardioverter defibrillator with a low false alarm rate.

INTRODUCTION: A wearable cardioverter defibrillator (WCD) is indicated in appropriate patients to reduce the risk for sudden cardiac death. Challenges for patients wearing a WCD have been frequent false shock alarms primarily due to electrocardiogram noise and wear discomfort. The objective of this study was to test a contemporary WCD designed for reduced false shock alarms and improved comfort. METHODS: One hundred and thirty patients with left ventricular ejection fraction ≤40% and an active implantable cardioverter defibrillator (ICD) were fitted with the ASSURE WCD (Kestra Medical Technologies) and followed for 30 days. WCD detection was enabled and shock alarm markers recorded, but shocks and shock alarms were disabled. All WCD episodes and ICD ventricular tachycardia/ventricular fibrillation (VT/VF) episodes were adjudicated. The primary endpoint was the false-positive shock alarm rate with a performance goal of 1 every 3.4 days (0.29 per patient-day). RESULTS: Of 163 WCD episodes, 4 were VT/VF and 159 non-VT/VF (121 rhythms with noise, 32 uncertain with noise, 6 atrial flutter without noise). Only three false-positive shock alarm markers were recorded; one false-positive shock alarm every 1333 patient-days (0.00075 per patient-day, 95% confidence interval: 0.00015-0.00361; p < .001). No ICD recorded VT/VF episodes meeting WCD detection criteria (≥170 bpm for ≥20 s) were missed by the WCD during 3501 patient-days of use. Median wear was 31.0 days (interquartile range [IQR] 2.0) and median daily use 23.0 h (IQR 1.7). Adverse events were mostly mild: skin irritation (19.4%) and musculoskeletal discomfort (8.5%). CONCLUSION: The ASSURE WCD demonstrated a low false-positive shock alarm rate, low patient-reported discomfort, and no serious adverse events.

Effect of stoichiometry on crosslinked epoxy resin characteristics: structural heterogeneities, topological defects, properties, free volume and segmental mobility.

Experimental studies have shown that changes in stoichiometry (R, ratio of amine groups to epoxy groups) cause considerable variations in the properties of epoxy-amine systems. Rationales based on free volume concepts have been routinely used to address these variations in properties but have hardly been satisfactorily substantiated. Many of these rationales remain as unverified conjectures to date. Substantiating these rationales will certainly bolster our understanding of the structure-stoichiometry-property relationship, but is difficult, due to inherent challenges involved in unambiguously characterizing the structural heterogeneities induced by changes in stoichiometry (structural heterogeneities include compositional distribution in the functionality of monomers, non-uniform dispersion of elastic chains and topological defects). The aim of the present work is to gain molecular-level insights into this relationship and to verify the rationales that rely on free volume concepts used for addressing the variations in properties with stoichiometry, with the help of all-atom molecular dynamics (MD) simulations. Five epoxy-amine systems with varying R ranging from 0.4 to 3, including the stoichiometric system (R = 1), were considered for these purposes. The properties of interest namely density, glass transition temperature (Tg) and thermal expansion coefficient in the rubbery state (αrl) of these systems were predicted. The local structure, fractional free volume and segmental mobility of these systems were then subsequently characterized as a function of stoichiometry and the results were analysed in detail. The role played by defects in properties and fractional free volume was then investigated. The results revealed significant insights into the compositional distribution of monomers with different functionalities as well as offered insights into the dispersion state and mobility of dangling chains, sols and elastic chains in the systems. Further, strong correlations were found between defect composition, fractional free volume at an elevated temperature (600 K) and thermomechanical properties (Tg and αrl) and it was established that the key mechanism underlying these correlations was the plasticization caused by defects. Analysis based on the rule of mixture models showed that these correlations were found to be in good agreement with the interpretations based on free volume concepts. The results also revealed a strong negative correlation between fractional free volume at room temperature and defect composition, a phenomenon typically associated with the antiplasticization effect.

Exploration of marine red seaweed as a dietary fish meal replacement and its potentiality on growth, hematological, biochemical, and enzyme activity in freshwater fish Labeo rohita.

The present study investigated the dietary fishmeal replacement by marine red seaweed (Halymenia dilatata) meal (RSM) on growth performance, feed utilization, chemical body composition, hematological constituents, digestive, antioxidant, and metabolic enzymes in freshwater fish Labeo rohita (Rohu) fingerlings. The fish were fed with RSM-free control diet (RSM0) and four experimental diets, which replaced fish meal (FM) with varying levels of RSM (25%, 50%, 75%, and 100%, represented as RSM25, RSM50, RSM75, and RSM100 respectively). After a 60-day feeding trial, the survival rate (SR), growth performance (length gain, weight gain, and specific growth rate), protein efficiency ratio, chemical body composition (protein, lipid, and ash), and digestive enzymes (amylase and protease) were significantly increased (P < 0.05) in the fish fed with RSM50 diet containing 39% protein level. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a higher staining intensity of muscle proteins in fish fed with the RSM50 diet. However, the hematological constituents (hemoglobin, hematocrit, red blood cell, white blood cell, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration), antioxidant enzyme - superoxide dismutase, and metabolic enzymes (glutamic oxaloacetic transaminase and glutamic pyruvic transaminase) were not significantly altered in RSM50 diet when compared to control. In contrast, hematological constituents were decreased (P < 0.05), and antioxidant and metabolic enzymes were increased in rohu fed with RSM75 and RSM100 (P < 0.05). Furthermore, these findings suggest that RSM might be adopted at a pace of 37% (estimated polynomial second-order regression) and is found to be beneficial for freshwater fish L. rohita diets that enhance growth and immune responses. The current study recommended substituting (50%) of marine red seaweed (Halymenia dilatata) for fish meal significantly improves the growth performance, chemical body composition, and digestive enzymes of L. rohita and this could be a valuable natural replacement for fishmeal to reduce the production cost of aquatic feed.

Effects of intravesical prostaglandin E2 on bladder function are preserved in capsaicin-desensitized rats.

Prostaglandin E2 (PGE2) instilled into the bladder generates symptoms of urinary urgency in healthy women and reduces bladder capacity and urethral pressure in both humans and female rats. Systemic capsaicin desensitization, which causes degeneration of C-fibers, prevented PGE2-mediated reductions in bladder capacity, suggesting that PGE2 acts as an irritant (Maggi CA, Giuliani S, Conte B, Furio M, Santicioli P, Meli P, Gragnani L, Meli A. Eur J Pharmacol 145: 105-112, 1988). In the present study, we instilled PGE2 in female rats after capsaicin desensitization but without the hypogastric nerve transection that was conducted in the Maggi et al. study. One week after capsaicin injection (125 mg/kg sc), rats underwent cystometric and urethral perfusion testing under urethane anesthesia with saline and 100 µM PGE2. Similar to naïve rats, capsaicin-desensitized rats exhibited a reduction in bladder capacity from 1.23 ± 0.08 mL to 0.70 ± 0.10 mL (P = 0.002, n = 9), a reduction in urethral perfusion pressure from 19.3 ± 2.1 cmH2O to 10.9 ± 1.2 cmH2O (P = 0.004, n = 9), and a reduction in bladder compliance from 0.13 ± 0.020 mL/cmH2O to 0.090 ± 0.014 mL/cmH2O (P = 0.011, n = 9). Thus, changes in bladder function following the instillation of PGE2 were not dependent on capsaicin-sensitive pathways. Further, these results suggest that urethral relaxation/weakness and/or increased detrusor pressure as a result of decreased compliance may contribute to urinary urgency and highlight potential targets for new therapies for overactive bladder.

Effects of graded levels of mineral mixtures (Aquamin® and Agrimin®) supplemented diets on growth, survival, proximate composition, and carcass mineralization of juvenile freshwater prawn, Macrobrachium malcolmsonii (H Milne-Edwards 1844).

The present study investigated the effects of Aquamin® mineral mixture (AQMM) and Agrimin® mineral mixture (AGMM) supplemented diets on growth and chemical composition of juvenile freshwater prawn Macrobrachium malcolmsonii (H. Milne-Edwards, 1844). Experimental diets containing 6 different AQMM levels (Trial 1: 0, 0.5, 1.0, 1.5, 2.0, and 2.5%) and 6 different AGMM levels (Trial 2: 0, 0.5, 1.0, 1.5, 2.0, and 2.5%) were formulated to feed juvenile prawn [initial body weight of 0.82 ± 0.05 g (Trial 1) and 1.24 ± 0.03 g (Trial 2)] for 60 days. Prawn fed diets containing 1.0% of AQMM and AGMM showed significantly increased (P < 0.05) survival rate, weight gain, specific growth rate, protein efficiency ratio, edible flesh weight, and proximate composition (moisture, crude protein, crude fat, and ash), while feed intake and feed conversion ratio were significantly decreased (P < 0.05). Whereas, 1.5-2.5% of AQMM- and AGMM-supplemented diets fed prawn showed a reverse trend when comparing other groups. Moreover, the minerals (macro elements: Ca, P, Mg, Na, and K; trace elements: Cu, Zn, and Fe) were significantly increased (P < 0.05) in the carcass of prawn when fed with 2.5% AQMM- and AGMM-supplemented diets. The present results suggest that the optimal dietary supplementation of AQMM and AGMM at a concentration of up to 1.06 and 1.02%, respectively (based on polynomial regression analysis), improved growth and enhanced the crude protein level of juvenile prawn.

Stimulation of the pelvic nerve increases bladder capacity in the PGE2 cat model of overactive bladder.

Selective electrical stimulation of the pudendal nerve exhibits promise as a potential therapy for treating overactive bladder (OAB) across species (rats, cats, and humans). More recently, pelvic nerve (PelN) stimulation was demonstrated to improve cystometric bladder capacity in a PGE2 rat model of OAB. However, PelN stimulation in humans or in an animal model that is more closely related to humans has not been explored. Therefore, our objective was to quantify the effects of PGE2 and PelN stimulation in the cat. Acute cystometry experiments were conducted in 14 α-chloralose-anesthetized adult, neurologically intact female cats. Intravesical PGE2 decreased bladder capacity, residual volume, threshold contraction pressure, and mean contraction pressure. PelN stimulation reversed the PGE2-induced decrease in bladder capacity and increased evoked external urethral sphincter electromyographic activity without influencing voiding efficiency. The increases in bladder capacity generated by PelN stimulation were similar in the rat and cat, but the stimulation parameters to achieve this effect differed (threshold amplitude at 10 Hz in the rat vs. twice threshold amplitude at 1 Hz in the cat). These results highlight the potential of PGE2 as a model of OAB and provide further evidence that PelN stimulation is a promising approach for the treatment of OAB symptoms.

Dynamic voltage threshold adjusted substrate modification technique for complex atypical atrial flutters with varying circuits.

BACKGROUND: Atypical atrial flutter (AFL) is common in patients with postsurgical atrial scar, with macro- or microscopic channels in the scar acting as substrate for reentry. Heterogeneous atrial scarring can cause varying flutter circuits, which makes mapping and ablation challenging, and recurrences common. AIM: We hypothesize that dynamically adjusting voltage thresholds can identify heterogeneous atrial scarring, which can then be effectively homogenized to eliminate atypical AFLs. METHODS: We studied consecutive patients who presented to Electrophysiology laboratory for atypical AFL ablation with history of atriotomy and included the patients with multiple, varying flutter circuits during mapping in our study. We excluded patients with stable flutter circuit that was sustained and could be localized using traditional entrainment and activation mapping strategy. In the included patients, we performed detailed high-density voltage map of the atrium of interest. We adjusted voltage thresholds as needed to identify heterogeneity and channels in the scarred regions. A thorough scar homogenization was performed with irrigated smart-touch ablation catheter. Re-inducibility of tachycardia, and immediate and long-term outcomes were studied. RESULTS: Of five studied cases, one was female; age 66 ± 10 years. All five had prior surgical substrate. All the patients had multiple flutter morphologies, which varied as we mapped the AFL. After scar homogenization, tachycardia was not inducible in any patient. No recurrence of flutter was noted during a mean follow-up duration of 450 ± 27 days. CONCLUSION: High-density voltage mapping and homogenization of the scar can be an effective strategy in eliminating complex scar-mediated atypical AFL with multiple circuits.

Apical splenic nerve electrical stimulation discloses an anti-inflammatory pathway relying on adrenergic and nicotinic receptors in myeloid cells.

The autonomic nervous system innervates all lymphoid tissues including the spleen therefore providing a link between the central nervous system and the immune system. The only known mechanism of neural inhibition of inflammation in the spleen relies on the production of norepinephrine by splenic catecholaminergic fibers which binds to ß2-adrenergic receptors (ß 2-ARs) of CD4+ T cells. These CD4+ T cells trigger the release of acetylcholine that inhibits the secretion of inflammatory cytokines by macrophages through α7 nicotinic acetylcholine receptor (α7nAchRs) signaling. While the vagal anti-inflammatory pathway has been extensively studied in rodents, it remains to be determined whether it coexists with other neural pathways. Here, we have found that three nerve branches project to the spleen in mice. While two of these nerves are associated with an artery and contain catecholaminergic fibers, the third is located at the apex of the spleen and contain both catecholaminergic and cholinergic fibers. We found that electrical stimulation of the apical nerve, but not the arterial nerves, inhibited inflammation independently of lymphocytes. In striking contrast to the anti-inflammatory pathway mechanism described so far, we also found that the inhibition of inflammation by apical nerve electrical stimulation relied on signaling by both ß 2-ARs and α7nAchRs in myeloid cells, with these two signaling pathways acting in parallel. Most importantly, apical splenic nerve electrical stimulation mitigated clinical symptoms in a mouse model of rheumatoid arthritis further providing the proof-of-concept that such an approach could be beneficial in patients with Immune-mediated inflammatory diseases.

Stimulation of the sensory pudendal nerve increases bladder capacity in the rat.

Pudendal nerve stimulation is a promising treatment approach for lower urinary tract dysfunction, including symptoms of overactive bladder. Despite some promising clinical studies, there remain many unknowns as to how best to stimulate the pudendal nerve to maximize therapeutic efficacy. We quantified changes in bladder capacity and voiding efficiency during single-fill cystometry in response to electrical stimulation of the sensory branch of the pudendal nerve in urethane-anesthetized female Wistar rats. Increases in bladder capacity were dependent on both stimulation amplitude and rate. Stimulation that produced increases in bladder capacity also led to reductions in voiding efficiency. Also, there was a stimulation carryover effect, and increases in bladder capacity persisted during several nonstimulated trials following stimulated trials. Intravesically administered PGE2 reduced bladder capacity, producing a model of overactive bladder (OAB), and sensory pudendal nerve stimulation again increased bladder capacity but also reduced voiding efficiency. This study serves as a basis for future studies that seek to maximize the therapeutic efficacy of sensory pudendal nerve stimulation for the symptoms of OAB.

Stimulation of the pelvic nerve increases bladder capacity in the prostaglandin E2 rat model of overactive bladder.

Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial for the treatment of OAB. Therefore our motivation was to test the hypothesis that PelN stimulation would increase bladder capacity in the prostaglandin E2 (PGE2) rat model of OAB. Cystometry experiments were conducted in 17 urethane-anesthetized female Sprague-Dawley rats. The effects of intravesical PGE2 vs. vehicle and PelN stimulation after intravesical PGE2 on cystometric parameters were quantified. Intravesical infusion of PGE2 resulted in decreased bladder capacity and increased voiding efficiency without a change in bladder contraction area under the curve, maximum contraction pressure, or contraction duration. Bladder capacity was also significantly decreased compared with vehicle (1% ethanol in saline) confirming that the change in bladder capacity was mediated by PGE2 PelN stimulation reversed the PGE2-induced change in bladder capacity and increased the external urethral sphincter electromyogram activity at a specific stimulation condition (amplitude of 1.0 times threshold at 10 Hz). These results confirm that the urodynamic changes reported in conscious rats are also observed under urethane anesthesia and that PelN stimulation is a novel and promising approach for the treatment of the symptoms of OAB.

OAB without an overactive bladder in the acute prostaglandin E2 rat model.

Intravesical prostaglandin E2 (PGE2) was previously used to induce overactive bladder (OAB) symptoms, as it reduces bladder capacity in rats and causes a "strong urgency sensation" in healthy women. However, the mechanism by which this occurs is unclear. To clarify how PGE2 reduces bladder capacity, 100 µM PGE2 was administered intravesically during open, single-fill cystometry with simultaneous measurement of sphincter EMG in the urethane-anesthetized female Wistar rat. PGE2 was also applied to the urethra or bladder selectively by use of a ligature at the bladder neck before (urethra) or during (bladder) closed-outlet, single-fill cystometry. Additional tests of urethral perfusion with PGE2 were made. PGE2 decreased bladder capacity, increased voiding efficiency, and increased sphincter EMG during open cystometry compared with saline controls. The number of nonvoiding contractions did not change with PGE2; however, bladder compliance decreased. During closed-outlet cystometry, PGE2 applied only to the bladder or the urethra did not decrease bladder capacity. Urethral infusion of PGE2 decreased urethral perfusion pressure. Taken together, these results suggest that intravesical PGE2 may decrease bladder capacity by targeting afferents in the proximal urethra. This may occur through urethral relaxation and decreased bladder compliance, both of which may increase activation of proximal urethra afferents from distension of the proximal urethra. This hypothesis stands in contrast to many hypotheses of urgency that focus on bladder dysfunction as the primary cause of OAB symptoms. Targeting the urethra, particularly urethral smooth muscle, may be a promising avenue for the design of drugs and devices to treat OAB.

Inverse Correlation of Venous Brain Natriuretic Peptide Levels with Body Mass Index Is due to Decreased Production.

OBJECTIVE: The aim of this paper was to study the association between body mass index (BMI) and coronary sinus (CS) brain natriuretic peptide (BNP) levels in patients with heart failure and reduced systolic function (HFrEF). BACKGROUND: There is an inverse relationship between systemic venous BNP (V-BNP) levels and BMI in patients with HFrEF. It is unclear whether this finding is due to decreased production or due to an increased metabolism of BNP. Since CS-BNP levels reflect BNP production, we hypothesized that assessing the correlation of CS-BNP levels with BMI would provide insight into the mechanism of this inverse relationship of V-BNP and BMI. METHODS: We prospectively enrolled 54 subjects with HFrEF who were to undergo cardiac resynchronization device implantation. CS-BNP, V-BNP, and arterial BNP (A-BNP) levels were measured during the implant procedure. Subjects were divided into 2 groups based on their BMI (group 1: BMI <30 and group 2: BMI ≥30). RESULTS: The mean age of the overall study group was 64 ± 10 years. Average BMI for group 1 was 25.8 ± 2.8 and 36.8 ± 4.6 for group 2 (p < 0.03). A history of hypertension was present in 55% (n = 26) of the subjects, while diabetes was reported in 31% (n = 15). Serum creatinine was 1.0 ± 0.2 mg/dL and TSH 2.1 ± 1.4 mIU/L. 79% of the subjects were receiving ß-blockers, while 94% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The mean CS-BNP, V-BNP, and A-BNP levels in group 2 were significantly lower than in group 1 (286.2 ± 170.5 vs. 417.5 ± 247.5 pg/mL, p = 0.04; 126.6 ± 32.5 vs. 228 ± 96.4 pg/mL, p = 0.01; and 151.9 ± 28.6 vs. 242 ± 88.8 pg/mL, p = 0.04, respectively). Univariate analysis and multivariate regression adjusted for age, diabetes mellitus, sex, glomerular filtration rate, and left atrial size confirmed BMI as an independent predictor of CS-BNP levels (ß = -0.372, p = 0. 03) in our study. CONCLUSIONS: In this study, we demonstrate an inverse relationship between CS-BNP levels and BMI in patients with HFrEF. These findings suggest that the previously established inverse relationship between V-BNP and BMI is due to a decreased cardiac production of BNP in obese patients rather than from increased peripheral metabolism.

Cardiac Implantable Electronic Device-Related Infection and Extraction Trends in the U.S.

BACKGROUND: Implantation of cardiac implanted electronic device (CIED) has surged lately. This resulted in a rise in cardiac device-related infections (CDI) and inevitably, lead extractions. We examined the recent national trend in the incidence of CIED infections and lead extractions in hospitalized patients and associated mortality. METHODS: Using the Nationwide Inpatient Sample for the years 2003-2011 we identified patients diagnosed with a CDI-associated infection as determined by discharge ICD-9 diagnostic codes. We examined the trend of device-related infections overall and in different subgroups. We studied mortality associated with device infections, lead extractions, associated costs, and length of stay. RESULTS: There is a significant increase in the number of hospitalizations due to CDI from 5,308 in the year 2003 to 9,948 in 2011. Males (68%), Caucasians (77%), and age group 65-84 years (56.4%) accounted for majority of CDI. The mortality associated with CDI was 4.5 %, and was worse in higher age groups (2.5% in 18-44 years compared to 5.3% in 85+ years, P < 0.001). Average length of stay was unchanged over the years remaining at 13.6 days; however, mean hospitalization charges increased from $91,348 in 2003 to $173,211 in 2011 (P < 0.001). Among all lead extraction procedures, the percentage of patients undergoing lead extraction secondary to CDI also increased from 2003 (59.1%) to 2011 (76.7%), P-value < 0.001. CONCLUSIONS: Healthcare burden associated with CDI infections and associated lead extractions has significantly increased in the recent years. Despite an increase in cost associated with CIED infections, mortality remains the same, and is higher in older patients.

Incidence, predictors and outcomes of hematoma after ICD implantation: An analysis of a nationwide database of 85,276 patients.

BACKGROUND: Pocket hematoma is one of the most common complications following cardiac device implantation. This study examined the impact of this complication on in-hospital outcomes following Implantable Cardioverter Defibrillator (ICD) implantation. METHODS: Data from Nationwide Inpatient Sample (NIS) 2010 was queried to identify all primary implantations of ICDs and Cardiac Resynchronization Therapy Defibrillators (CRT-D) during the year 2010 using ICD-9 codes. We then identified the patients who experienced a procedure related hematoma during the hospital stay. We compared the outcomes of the patients with and without a hematoma complication. All analyses were performed using SPSS 20 complex samples using appropriate weights to adjust for the complex sampling design of the national database. RESULTS: Out of a total of 85,276 primary ICD implantations in the year 2010, 2233 (2.6% of the implantations) were complicated by a hematoma. Increased age (p < 0.001), and comorbidities such as congestive heart failure (odds ratio (OR) - 1.86, p < 0.001), coagulopathy (OR - 2.3, p < 0.001) and renal failure (OR - 1.52, p < 0.001) were associated with an increased risk of pocket hematoma formation. Patients who developed a hematoma had a longer hospitalization (9.1 days versus 5.5 days, p < 0.001) and higher in-hospital costs ($56,545 versus $47,015, p < 0.001) compared to patients who did not have a hematoma. Overall mortality associated with ICD implantation was low (0.6%), and hematoma formation did not adversely affect mortality (0.6% versus 0.4%, p = 0.63). CONCLUSION: Hematoma occurs infrequently after ICD implantation, however, it adversely impacts the cost of procedure and length of stay.

Impact of haematoma after pacemaker and CRT device implantation on hospitalization costs, length of stay, and mortality: a population-based study.

AIMS: Pocket haematoma is a common complication following pacemaker implantation. Impact of this complication on post-procedural outcomes has previously not been systematically studied. We sought to identify the incidence of pocket haematoma after a de novo pacemaker and cardiac resynchronization therapy (CRT) device implantation and evaluate its impact on the hospital outcomes using a large all-payer national inpatient database. METHODS AND RESULTS: Data from Nationwide Inpatient Sample 2010 was queried to identify all primary implantations of single chamber, dual chamber pacemakers, and biventricular devices during the year 2010 using the appropriate ICD-9 codes. Patients who experienced a procedure-related haematoma during the hospital stay were identified. Of a total of 78,751 primary pacemaker implantations in the year 2010, 1677 (2.1%) of the implantations were complicated by a pocket haematoma. Higher age groups, more complex pacemaker types (BiV > dual chamber > single chamber), and comorbidities such as congestive heart failure and coagulopathy were associated with an increased risk of pocket haematoma formation post-pacemaker implantation. Patients who developed a pocket haematoma had a longer length of stay (8.7 vs. 4.8 days, P < 0.001), higher hospitalization costs ($48,815 vs. $34,324, P < 0.001) and higher in-hospital mortality (2.0 vs. 0.7%, P < 0.001) compared with patients who did not develop a haematoma. CONCLUSIONS: Haematoma is a relatively common complication associated with pacemaker implantation; however, it adversely impacts in-hospital outcomes.