Comparison of in-hospital outcomes and complications of left atrial appendage closure with the Watchman device between males and females.

AIMS: Left atrial appendage occlusion (LAAO) with WATCHMAN device is being used for patients with atrial fibrillation (AFB) and, as an off-label use, atrial flutter (AFL) who can't comply with long-term anticoagulation. We aim to study the differences in outcomes between sexes in patients undergoing Watchman device implantation. METHODOLOGY: The National Inpatient Sample was queried between 2016 and 2019 using ICD-10 clinical modification codes I48x for AFB and AFL. Patients who underwent LAAO were identified using the procedural code 02L73DK. Comorbidities and complications were identified using ICD procedure and diagnosis codes. Differences in primary outcomes were analyzed using multivariable regression and propensity score matching. RESULTS: 38 105 admissions were identified, of which 16 795 (44%) were females (76 ± 7.6 years) and 21 310 (56%) were males (75 ± 8 years). Females were more likely to have cardiac (frequencies: 5.8% vs 3.75%, aOR: 1.5 [1.35-1.68], p1 day inpatient (1.79 [1.67-1.93], P < 0.01) and be discharged to a facility (1.54 [1.33-1.80], P < 0.01). CONCLUSION: Females are more likely to develop cardiac, renal, bleeding, pulmonary and TEE-related complications following LAAO procedure, while concurrently showing higher mortality, length of stay and discharge to facilities.

The metabolites could not be ignored: A comparative study of the metabolite norfluoxetine with its parent fluoxetine on zebrafish (Danio rerio).

The ubiquitous pharmaceuticals in aquatic environments have attracted huge attention due to their significant risks to humans and ecosystems. However, even though the knowledge of the negative effects induced by the parent pharmaceuticals is quite extensive, little is known about their metabolites for a long time. This study provides systematical knowledge about the potential toxicity of metabolite norfluoxetine and its parent fluoxetine on zebrafish (Danio rerio) at the early life stage. The results showed that the metabolite norfluoxetine had similar acute toxicity in fish with the parent fluoxetine. For the altered fish development, there was no significant difference in most cases between the two pharmaceuticals. Compared to the control, the metabolite markedly inhibited the locomotor behavior under light-to-dark transitions, which was comparable to the parent. Norfluoxetine could easily accumulate but hardly eliminate from fish, relative to fluoxetine. In addition, the accumulated fluoxetine in zebrafish may rapidly metabolize to norfluoxetine and then be eliminated through different metabolic pathways. The functional genes related to serotonergic process (5-ht1aa, 5-ht2c, slc6a4b, and vmat), early growth (egr4), and circadian rhythm (per2) were downregulated by both the norfluoxetine and fluoxetine, indicative of the same mode-of-action of norfluoxetine with its parent in these functions. Meanwhile, the alterations caused by norfluoxetine were more pronounced than that of fluoxetine in the genes of 5-ht2c, slc6a4b, vmat, and per2. The molecular docking also confirmed that norfluoxetine could bind with serotonin transporter protein in the same as fluoxetine with a lower binding free energy. Overall, the metabolite norfluoxetine could induce similar and even more toxic effects on zebrafish with the same mode of action. The different and binding energy of the metabolite norfluoxetine and its parent fluoxetine on zebrafish may be responsible for the differentiated effects. It highlights the risks of the metabolite norfluoxetine in the aquatic environment could not be ignored.

Distribution, Bioaccumulation, and Risks of Pharmaceutical Metabolites and Their Parents: A Case Study in an Yunliang River, Nanjing City.

The occurrence, bioaccumulation, and risks of 11 pairs of pharmaceutical metabolites and their respective parents were investigated in the water, sediment, and fish of an urban river in Nanjing city, China. The results showed that most of the target metabolites and their parents were detected in all water samples, with concentrations ranging from 0.1 ng/L to 72.9 ng/L. In some cases, the concentrations of metabolites in water were significantly higher than their parents, with fold changes reaching up 4.1 in the wet season and 6.6 in the dry season, while in sediment and fish, a lower concentration was observed in most cases. A lowered concentration of detected pharmaceuticals was observed in the dry season when compared to the wet season due to the seasonal variation in pharmaceutical consumption and overflow effluent. The bioaccumulation of pharmaceuticals in different fish tissues were detected with a descending order of overall concentration as gill > brain > muscle > gonad > intestine > liver > blood. In addition, the concentrations of both metabolites and their parents also decreased along the river in two seasons. However, the concentration rates of metabolites and their parents were significantly altered along the river in both water and sediment. The relatively high concentration proportions of the detected pharmaceuticals in water suggested that pharmaceuticals were more likely to apportion in water than in sediment, especially for the metabolites. Meanwhile, the rates of the metabolite/parent pairs between fish and water/sediment were generally lower, indicating the higher excretion capacity of metabolites from fish than their parents. Most of the detected pharmaceuticals had no impact on aquatic organisms. However, the presence of ibuprofen posed a medium risk to fish. Compared to the parents, metabolites showed a relatively low risk value but a high contribution to the total risk. It highlights that metabolites in the aquatic environments cannot be ignored.

Gut Microbes in Immunoglobulin A Nephropathy and Their Potential Therapeutic Applications.

Microbial ecosystem consists of a complex community of bacterial interactions and its host microenvironment (tissue, cell, metabolite). Because the interaction between gut microbiota and host involves many diseases and seriously affects human health, the study of the interaction mechanism between gut microbiota and host has attracted great attention. The gut microbiome is made up of 100 trillion bacteria that have both beneficial and adverse effects on human health. The development of IgA Nephropathy results in changes in the intestinal microbial ecosystem that affect host physiology and health. Similarly, changes in intestinal microbiota also affect the development of IgA Nephropathy. Thus, the gut microbiome represents a novel therapeutic target for improving the outcome of IgA Nephropathy, including hematuria symptoms and disease progression. In this review, we summarize the effect of intestinal microbiota on IgA Nephropathy in recent years and it has been clarified that the intestinal microbiota has a great influence on the pathogenesis and treatment of IgA Nephropathy.

Clinical presentation, diagnosis, and treatment of atrioesophageal fistula resulting from atrial fibrillation ablation.

BACKGROUND: Atrioesophageal fistula (AEF) is a worrisome complication of atrial fibrillation (AF) ablation. Its clinical manifestations and time course are unpredictable and may contribute to diagnostic and treatment delays. We conducted a systematic review of all available cases of AEF, aiming at characterizing clinical presentation, time course, diagnostic pitfalls, and outcomes. METHODS: The digital search retrieved 150 studies containing 257 cases, 238 (92.6%) of which with a confirmed diagnosis of AEF and 19 (7.4%) of pericardioesophageal fistula. RESULTS: The median time from ablation to symptom onset was 21 days (interquartile range [IQR]: 11-28). Neurological abnormalities were documented in 75% of patients. Compared to patients seen by a specialist, those evaluated at a walk-in clinic or community hospital had a significantly greater delay between symptom onset and hospital admission (median: 2.5 day [IQR: 1-8] vs. 1 day [IQR: 1-5); p = .03). Overall, 198 patients underwent a chest scan (computed tomography [CT]: 192 patients and magnetic resonance imaging [MRI]: 6 patients), 48 (24.2%; 46 CT and 2 MRI) of whom had normal/unremarkable findings. Time from hospital admission to diagnostic confirmation was significantly longer in patients with a first normal/unremarkable chest scan (p < .001). Overall mortality rate was 59.3% and 26.0% survivors had residual neurological deficits at the time of discharge. CONCLUSIONS: Since healthcare professionals of any specialty might be involved in treating AEF patients, awareness of the clinical manifestations, diagnostic pitfalls, and time course, as well as an early contact with the treating electrophysiologist for a coordinated interdisciplinary medical effort, are pivotal to prevent diagnostic delays and reduce mortality.

Mixed Effect Modeling of Dose and Linear Energy Transfer Correlations With Brain Image Changes After Intensity Modulated Proton Therapy for Skull Base Head and Neck Cancer.

PURPOSE: Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT. METHODS AND MATERIALS: For 15 patients with RAIC after IMPT, contrast enhancement observed on T1-weighted magnetic resonance imaging was contoured and coregistered to the planning computed tomography. Monte Carlo calculated dose and dose-averaged LET (LETd) distributions were extracted at voxel level and associations with RAIC were modelled using uni- and multivariate mixed effect logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve and precision-recall curve. RESULTS: An overall statistically significant RAIC association with dose and LETd was found in both the uni- and multivariate analysis. Patient heterogeneity was considerable, with standard deviation of the random effects of 1.81 (1.30-2.72) for dose and 2.68 (1.93-4.93) for LETd, respectively. Area under the receiver operating characteristic curve was 0.93 and 0.95 for the univariate dose-response model and multivariate model, respectively. Analysis of the LETd effect demonstrated increased risk of RAIC with increasing LETd for the majority of patients. Estimated probability of RAIC with LETd = 1 keV/µm was 4% (95% confidence interval, 0%, 0.44%) and 29% (95% confidence interval, 0.01%, 0.92%) for 60 and 70 Gy, respectively. The TD15 were estimated to be 63.6 and 50.1 Gy with LETd equal to 2 and 5 keV/µm, respectively. CONCLUSIONS: Our results suggest that the LETd effect could be of clinical significance for some patients; LETd assessment in clinical treatment plans should therefore be taken into consideration.

Microplastic pollution in an urbanized river affected by water diversion: Combining with active biomonitoring.

Microplastics as the most challenging environmental pollutants in ocean have raised increasing concerns, however, the understanding of microplastics in freshwater falls far behind. The main objective of this study is to assess the microplastic pollution in an urbanized river affected by water diversion. The active biomonitoring method with caged native crucian carp (Carassius auratus) was used to evaluate the microplastic risk for riverine fish. It found that microplastic abundance in water and sediment was 1467-20567 items/m³ and 1115-6380 items/kg, respectively. The operational water diversion did not alleviate the microplastic pollution in water. The abundance in sediment was not simply proportional to that in water. However, the main morphological profiles and polymer composition were similar in the water and sediment. Microplastic accumulation in caged fish intestine was higher than that in gill. Intestine seems to be an ideal tissue to reflect the microplastic pollution in water. Shapes may contribute to the accumulation in fish. Based on the pollution load index, all caged fish did not reach to high level risks. These findings not only improve the understanding on the impact of water diversion on microplastic pollution in urban river, but also shed an insight in the related risk for riverine fish.

Influence of dissolved organic matter on the accumulation, metabolite production and multi-biological effects of environmentally relevant fluoxetine in crucian carp (Carassius auratus).

Fluoxetine is a widely prescribed antidepressant that has been frequently detected in aquatic environments and is associated with a series of neurological, behavioural and neuroendocrine disruptions in nontarget organisms. However, studies on its effects in fish under realistic environmental conditions are still limited. In this study, we determined the influences of an environmentally relevant concentration of fluoxetine (100 ng/L) on crucian carp (Carassius auratus) in the presence of dissolved organic matter (DOM). Endpoints that were assessed included accumulation of fluoxetine and metabolite formation as well as related biological responses involving neurotransmission and metabolic processes. Fluoxetine was significantly bioconcentrated in the fish brain and liver and largely transformed to the active metabolite norfluoxetine. Brain neurotransmission processes related to serotonin and choline and liver metabolic status were simultaneously altered. DOM added at 1 mg/L had no effect on the accumulation of fluoxetine or its metabolites in different tissues of the fish. However, at 10 mg/L DOM facilitated fluoxetine and norfluoxetine accumulation in the liver, brain, kidney, gill and bile tissues of the fish. The neuroendocrine-disrupting effects on fish caused by fluoxetine were also enhanced by the co-addition of DOM at 10 mg/L. Binding with fluoxetine and the inhibition of metabolic functions caused by DOM may be responsible for this increase in effects. These findings imply that at high concentrations DOM can increase the toxicity of environmentally relevant concentrations of fluoxetine to fish.

Residues, bioaccumulation, and trophic transfer of pharmaceuticals and personal care products in highly urbanized rivers affected by water diversion.

Little information is available on the bioaccumulation and trophic transfer of pharmaceuticals and personal care products (PPCPs) in urban rivers system, particularly for those affected by water transfer. Herein, a comprehensive study was conducted to investigate the biological residues, bioaccumulation and trophic transfer of 45 PPCPs in the Nanjing Qinhuai River system under the background of water diversion projects. A total of 30 compounds were detected with a descending order of overall concentration as plankton > benthic mollusc > fish (except grass carp). Higher biological residues were observed in the downstream than those in the upstream, with the largest increase for fish (136.4 %) and the lowest increase for phytoplankton (5.4 %). However, the bioaccumulation classifications of most PPCPs were unchanged among the three different water-diversion regions. Trophic magnification factors (TMFs) of organic UV filters (homosalate, oxybenzone, ethylhexyl methoxycinnamate and octocrylene) ranged from 1.23 to 2.04, suggesting trophic magnification potential, while trophic dilution for pharmaceuticals (sertraline, citalopram, caffeine and roxithromycin) with TMFs of 0.42 to 0.50 were observed. A notable positive correlation was observed between the pH-dependent distribution coefficient (logDow) and the TMFs of the PPCPs (P < 0.05). Although the human health hazard assessment indicated no immediate health risk via the consumption of freshwater food, attention should be paid to the joint effects of PPCPs.

Enhanced photocatalytic activity of a hydrogen bond-assisted 2D/2D Z-scheme SnNb2O6/Bi2WO6 system: Highly efficient separation of photoinduced carriers.

2D/2D materials have attracted extensive attention in the field of photocatalysis due to their large contact surfaces and short charge transfer distances. However, 2D/2D heterojunction materials, especially those that connect different materials together using strong chemical bonds, are still challenging to prepare. Herein, a novel hydrogen bond-assisted 2D/2D Z-scheme SnNb2O6/Bi2WO6 system was successfully prepared using a facile hydrothermal method. The 2D/2D Z-scheme system increases the accessible area for charges and constructs interfacial electric fields, thereby reducing the barriers for electron transport and enhancing the photocatalytic activity. In addition, the electronic coupling of the surface hydrogen bonds can further enhance the interfacial electric fields, which offers a new route for lowering the interfacial potential barrier of the system. As expected, the hydrogen bond-assisted 2D/2D Z-scheme SnNb2O6/Bi2WO6 system results in an outstanding improvement of the norfloxacin (NOR) photodegradation efficiency, and the degradation rate constant (4.06 × 10-2 min-1) is 9 and 2 times higher than those of SnNb2O6 (4.33 × 10-3 min-1), and Bi2WO6 (1.70 × 10-2 min-1), respectively. Simultaneously, three differently degradation pathways for the degradation of NOR were proposed based on the degradation products that were identified. Finally, a fast charge transfer mechanism of the hydrogen bonds that are connected to the 2D/2D Z-scheme SnNb2O6/Bi2WO6 system is proposed, which is based on the ESR analysis and the DFT calculations.

Clinical outcomes after intensity-modulated proton therapy with concurrent chemotherapy for inoperable non-small cell lung cancer.

BACKGROUND & PURPOSE: We report disease control, survival, and toxicity in patients with advanced inoperable non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy and intensity-modulated proton therapy (IMPT) at a single institution. MATERIAL AND METHODS: All patients were treated with IMPT with concurrent chemotherapy. Endpoints assessed were local, regional, and distant control, disease-free survival (DFS), and overall survival (OS). RESULTS: Fifty-one patients were enrolled with a median follow-up time of 23.0 months; 39 (76%) were treated with a simultaneous integrated boost to the gross tumor volume (GTV). The median GTV dose was 67.3 CGE and the median CTV dose was 60.0 CGE. Median OS and DFS times were 33.9 months and 12.6 months. The 3-year local control rate was 78.3%. Treatment was well tolerated, with a grade 3 toxicity rate of 18% (9 events: 4 esophagitis, 3 dermatitis, 1 esophageal stricture, and 1 fatigue) and no grade 4 or 5 toxicity. The most common grade 2 toxic effects were esophagitis (22 [43%]), dermatitis (16 [31%]), pain (15 [29%]), and fatigue (14 [27%]). CONCLUSIONS: Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity.

Transcriptional control of the main aromatic hydrocarbon efflux pump in Pseudomonas.

Bacteria of the species Pseudomonas putida are ubiquitous soil inhabitants, and a few strains are able to thrive in the presence of extremely high concentrations of toxic solvents such as toluene and related aromatic hydrocarbons. Toluene tolerance is multifactorial in the sense that bacteria use a wide range of physiological and genetic changes to overcome solvent damage. This includes enhanced membrane impermeabilization through cis to trans isomerization of unsaturated fatty acids, activation of a stress response programme, and induction of efflux pumps that expulse toxic hydrocarbons to the outer medium. The most relevant element in this toluene tolerance arsenal is the TtgGHI efflux pump controlled by the TtgV regulator. We discuss here how TtgV controls expression of this efflux pump in response to solvents.

The collagen receptor DDR2 is expressed during early cardiac development.

Discoidin Domain Receptor 2 (DDR2) is a receptor tyrosine kinase which has been shown to regulate cell migration upon binding its ligand, collagen. Expression studies determined that DDR2 mRNA and protein are present in the atrioventricular canal during epithelial-mesenchymal transformation (EMT) and the receptor is expressed in both activated endothelial and migrating mesenchymal cells in vivo.

A single 24F Blake drain after wedge resection or lobectomy: a study on 100 consecutive cases.

OBJECTIVE: To evaluate the results of chest drainage using one 24F Blake drain after standard thoracic operations (wedge resection and lobectomy). METHODS: In 2005, 100 consecutive patients underwent drainage of their pleural cavity following lobectomy or wedge resection(s). There were 70 men and 30 women, with a mean age of 55 years (17-83). There were 47 lobectomies (23 upper, 5 middle, 19 lower), 3 bilobectomies (2 right upper and middle, 1 right lower and middle), and 2 anatomical segmentectomies. All these anatomical resections were performed by standard thoracotomy, mainly for cancer diseases (45 cases). Furthermore, 48 atypical resections by single or multiple wedge(s) were realized, 20 of them by VATS. They included 14 various benign diseases, 16 malignant diseases, 8 significant emphysema bullous, and 10 blebs. Chest X rays were performed regularly in the postoperative period to detect residual pleural effusion or pneumothorax necessitating additional drainage or reoperation. Patients were controlled one month after discharge. RESULTS: One patient with pleural carcinosis died of pulmonary embolus on day 8. Neither replacement of chest tube nor reoperation was necessary for pleural space problems. Median duration of drainage was 5 days (3-15), 6 days after lobectomy and 4 days after wedge resection. In 15 cases, the duration of drainage was more than 8 days: 11 persistent air leaks and 4 drainages exceeding 150-200 cm3 daily. Ninety percent of patients were discharged the day following the drain removal. CONCLUSIONS: Postoperative courses after standard thoracic procedures using a single 24F Blake drainage appear similar to that accounting after a classical semi-rigid drainage. Such single drainage may appear now as an acceptable option. The flexible quality of the drain, its reduced caliber, and the character unique of the drainage, may contribute to improve comfort of the operated patients.