Protective Effects of Statins on Limb and Cardiovascular Outcomes in Patients with Peripheral Artery Disease and End-Stage Renal Disease.

Background: Previous studies have reported that statins have inconsistent and marginal cardiovascular (CV) benefits in patients with end-stage renal disease (ESRD). However, whether statins play a secondary preventive role in patients with peripheral artery disease (PAD) and ESRD remains unclear. Objectives: This study aimed to compare the long-term clinical outcomes between statin users and nonusers with PAD and ESRD. Methods: This retrospective cohort study assessed the long-term protective effects of statins using data from the National Health Insurance Research Database in Taiwan. Propensity score matching was performed according to sex, age, index year, related comorbidities, and medications. The main outcomes were limb events and major adverse CV events (MACEs). Results: The statin user group (n = 4,460) was compared with the propensity score-matched statin nonuser group (n = 4,460). The mean age of the matched patients was 64 years, and 40% of the patients were men. The baseline characteristics of the groups were well-balanced. The overall limb event and MACE rates were not different between the two groups. However, the statin user group had lower rates of limb amputation [adjusted hazard ratio (aHR): 0.85, 95% confidence interval (CI): 0.73-0.99], stroke (aHR: 0.71, 95% CI: 0.62-0.83), CV death (aHR: 0.46, 95% CI: 0.32-0.66), and all-cause death (aHR: 0.45, 95% CI: 0.42-0.48) despite having a higher rate of percutaneous transluminal angioplasty for PAD. Conclusions: This population-based retrospective cohort study demonstrated that statin therapy was associated with a lower risk of limb amputation, nonfatal stroke, CV death, and all-cause death in patients with PAD and ESRD.

Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells.

Plasma levels of angiopoietin-2 are increased in patients with chronic kidney disease (CKD). Moreover, mouse models of progressive kidney disease also demonstrate increased angiopoietin-2 in both plasmas and kidneys. The role of dysregulated angiopoietins in the progression of kidney disease has not been thoroughly investigated. Here, we found in a cohort of 319 patients with CKD that plasma angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratios were positively associated with the development of kidney failure. In mice with progressive kidney disease induced by either ureteral obstruction or ischemia-reperfusion injury, overexpression of human angiopoietin-1 in the kidney tubules not only reduced macrophage infiltration in the initial stage post-injury but also attenuated endothelial cell apoptosis, microvascular rarefaction, and fibrosis in the advanced disease stage. Notably, angiopoietin-1 attenuated chemokine C-C motif ligand 2 (CCL2) expression in the endothelial cells of the fibrosing kidneys, and these protective effects led to attenuation of functional impairment. Mechanistically, angiopoietin-1 reduced CCL2-activated macrophage migration and protected endothelial cells against cell apoptosis induced by angiopoietin-2 and Wnt ligands. Based on this, we applied L1-10, an angiopoietin-2 inhibitor, to the mouse models of progressive kidney disease and found inhibitory effects on macrophage infiltration, microvascular rarefaction, and fibrosis. Thus, we defined the detrimental impact of increased angiopoietin-2 on kidney survival of patients with CKD which appears highlighted by angiopoietin-2 induced endothelial CCL2-activated macrophage infiltration and endothelial cell apoptosis in their kidneys undergoing fibrosis.

Comparison of the O-RADS and ADNEX models regarding malignancy rate and validity in evaluating adnexal lesions.

OBJECTIVE: This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions. METHODS: This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart. RESULTS: Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s). CONCLUSIONS: The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time. KEY POINTS: • Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. • Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.

Efficacy and Safety of "I-Stop-Mini Adjustable" Sling System versus Transobturator Midurethral "Obtryx" Sling System in Stress Urinary Incontinence: A Retrospective Cohort Study.

STUDY OBJECTIVE: To compare the safety, efficacy, and adverse events of the new mini-adjustable sling system "I-stop-mini" with transobturator midurethral slings "Obtryx" (Boston Scientific, Marlborough, MA) in women with stress urinary incontinence. DESIGN: A single-center, retrospective cohort study. SETTING: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan. PATIENTS: A total of 347 patients who underwent I-stop-mini or Obtryx for stress urinary incontinence treatment. INTERVENTIONS: Midurethral sling with either I-stop-mini or Obtryx. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were objective success and subjective cure rates between the 2 groups. Objective success was evaluated using a 1-hour pad test, and subjective cure was evaluated using a questionnaire score (Incontinence Impact Questionnaire, Urinary Distress Inventory, and International Consultation on Incontinence Questionnaire Short Form). Secondary outcomes were the evaluation of surgical outcomes, operative data, and adverse events between the 2 groups. In total, 171 of 200 I-stop-mini subjects and 127 of 147 Obtryx subjects completed 12 months of follow-up. Regarding the objective success between the I-stop-mini group and the Obtryx group, 1-month postoperative (3.6 ± 5.2 vs 3.9 ± 12.6; p = .765), 6-month postoperative (3.9 ± 5.1 vs 4.2 ± 12.6; p = .848), and 12-month postoperative (4.6 ± 5.6 vs 4.5 ± 13.6; p = .980) 1-hour pad tests showed no significant difference. The 12-month subjective cure rates decreased from 94.7% (1-month postoperative) to 91.2% (12-month postoperative) in the I-stop-mini group and 95.2% (1-month postoperative) to 85.0% (12-month postoperative) in the Obtryx group. Similar and durable efficacy was observed between the 2 groups. The I-stop-mini group had shorter operative times and hospital stays than the Obtryx group; however, both groups showed similar adverse event rates. CONCLUSION: The objective success and subjective cure rates of I-stop-mini did not differ to those of Obtryx. However, long-term data and further prospective studies on I-stop-mini are necessary to arrive at a definite conclusion.

Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision.

Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman's syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate-carboxymethylcellulose or polyethylene oxide-sodium carboxymethylcellulose as anti-adhesive barrier.

Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells.

The role of the epithelial-mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-ß1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-ß1 treatment. CSE or TGF-ß1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.

Low-Frequency Vibration Facilitates Post-Exercise Cardiovascular Autonomic Recovery.

It is important to use short breaks to accelerate post-exercise recovery in sports. Previous studies have revealed that vibration can reduce post-exercise muscle soreness. However, there is still high heterogeneity in the effects of vibration on cardiovascular autonomic activities, and most studies to date have focused on high-frequency vibration. This study aimed to investigate the effect of low-frequency lower-body vibration (LBV) on post-exercise changes in heart rate variability and peripheral arterial tone. Ten men and 9 women aged 20 to 25 were recruited for this study. Each subject visited the testing room three times with at least 2 days in between. Each time, the subject received one of the three different vibration frequencies (0, 5, and 15 Hz) in a random order in the sitting position for 10 minutes. LBV was performed immediately after a static standing (control) test and 3-min-step test. Heart rate variability and digital volume pulse wave were recorded during the vibration phase (V1: vibration 0-5 minutes; V2: 6-10 minutes) and the recovery phase (Rc1: recovery phase 11-15 minutes; Rc2: 16-20 minutes). The result of digital pulse wave analysis showed that the reflection index (RI) under 15 Hz decreased during V1. Heart rate of the 15-Hz group also decreased during Rc1 and Rc2. According to the analysis of heart rate variability, low-frequency power/high-frequency power (LF/HF) decreased and normalized high-frequency power (nHF) increased during V2, Rc1 and Rc2 under 15 Hz and, during Rc2 under 5 Hz vibration. This study confirmed that the application of low-frequency LBV after exercise can reduce peripheral vascular tone, accelerate heart rate recovery, decrease cardiac sympathetic nerve activity, and promote parasympathetic nerve activity. The effect was more pronounced at 15 Hz than at 5 Hz. The findings provide a method to accelerate cardiovascular autonomic recovery after exercise.

Defect-Accommodating Intermediates Yield Selective Low-Temperature Synthesis of YMnO3 Polymorphs.

In the synthesis of complex oxides, solid-state metathesis provides low-temperature reactions where product selectivity can be achieved through simple changes in precursor composition. The influence of precursor structure, however, is less understood in solid-state synthesis. Here we present the ternary metathesis reaction (LiMnO2 + YOCl → YMnO3 + LiCl) to target two yttrium manganese oxide products, hexagonal and orthorhombic YMnO3, when starting from three different LiMnO2 precursors. Using temperature-dependent synchrotron X-ray and neutron diffraction, we identify the relevant intermediates and temperature regimes of reactions along the pathway to YMnO3. Manganese-containing intermediates undergo a charge disproportionation into a reduced Mn(II,III) tetragonal spinel and oxidized Mn(III,IV) cubic spinel, which lead to hexagonal and orthorhombic YMnO3, respectively. Density functional theory calculations confirm that the presence of Mn(IV) caused by a small concentration of cation vacancies (∼2.2%) in YMnO3 stabilizes the orthorhombic polymorph over the hexagonal. Reactions over the course of 2 weeks yield o-YMnO3 as the majority product at temperatures below 600 °C, which supports an equilibration of cation defects over time. Controlling the composition and structure of these defect-accommodating intermediates provides new strategies for selective synthesis of complex oxides at low temperatures.

Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice.

BACKGROUND/PURPOSE: Substantial progress was made in acute kidney injury (AKI) over the past 10 years, but no therapeutic interventions have been shown to prevent AKI or accelerate functional recovery after injury. A large number of preclinical studies supports the use of recombinant human erythropoietin (rHuEPO) to prevent AKI, but the clinical trial data are inconclusive. To address concerns about preclinical study design and reporting in AKI, we here presented our rigorous experiments on the use of rHuEPO in a mouse model simulating the most common post-ischemic AKI in patients. METHODS: Use of saline vehicle or rHuEPO (100 or 1000 U/KgBW) in mice subjected to AKI induced by ischemia-reperfusion injury of left kidney 2 weeks after right nephrectomy (NX + IRI). RESULTS: NX + IRI resulted in a reproducible AKI model. Use of rHuEPO as a pretreatment or posttreatment did not affect AKI severity, functional recovery, and mouse survival regardless of gender, injury severity, or doses of rHuEPO. Administering rHuEPO with 1000 U/KgBW did increase hematocrit and modulate AKI kidney macrophages by Nos2 downregulation and Ccl17 upregulation. Active expression of erythropoietin receptor (EPOR) was not identified in renal cells by lineage tracing study, whereas expression of colony-stimulating factor 2 receptor ß (CSF2Rß) was identified in kidney macrophages and upregulated after AKI. Both EPOR and CSF2Rß were identified in cultured bone marrow derived macrophages, possibly mediated the robust inhibition of cytokine-induced phenotype switching by rHuEPO. CONCLUSION: Use of rHuEPO can modulate macrophage function but not the post-ischemic AKI severity, functional recovery and survival in mice.

A set of microsatellite markers to differentiate Plasmodium falciparum progeny of four genetic crosses.

BACKGROUND: Four Plasmodium falciparum genetic crosses (HB3×3D7, HB3×Dd2, 7G8×GB4, and 803×GB4) have produced sets of recombinant progeny that are widely used for malaria research, including investigations of anti-malarial drug resistance. It is critical to maintain the progeny free from cross-contamination. Microsatellite polymorphisms can be used to validate parasite identity. RESULTS: A set of 12 markers was developed that differentiates the parents of the four P. falciparum crosses. This typing set identified distinguishing patterns of inheritance (fingerprints) in segregant collections of 15 progeny clones from HB3×3D7, 32 from HB3×Dd2, 33 from 7G8×GB4, and 81 from 803×GB4. Stronger amplification was observed with shorter relative to longer alleles of individual microsatellites. In experiments with mixed parental DNAs, electropherograms showed that signals of cross-contamination can be missed when minor peaks less than 1/4 or 1/3 the height of the major peak are disregarded by threshold settings commonly used for population studies. CONCLUSIONS: Microsatellite typing is an effective method to check the identity of P. falciparum lines and detect parasite cross-contamination in cultures; however, care must be taken not to ignore minor peaks that can be overlooked. The 12 microsatellite markers presented here provide a rapid and efficient means to distinguish the segregants of laboratory crosses. Fingerprint patterns from these markers are useful to maintain the integrity of diverse parasite lines in and between research laboratories.

A HECT ubiquitin-protein ligase as a novel candidate gene for altered quinine and quinidine responses in Plasmodium falciparum.

The emerging resistance to quinine jeopardizes the efficacy of a drug that has been used in the treatment of malaria for several centuries. To identify factors contributing to differential quinine responses in the human malaria parasite Plasmodium falciparum, we have conducted comparative quantitative trait locus analyses on the susceptibility to quinine and also its stereoisomer quinidine, and on the initial and steady-state intracellular drug accumulation levels in the F1 progeny of a genetic cross. These data, together with genetic screens of field isolates and laboratory strains associated differential quinine and quinidine responses with mutated pfcrt, a segment on chromosome 13, and a novel candidate gene, termed MAL7P1.19 (encoding a HECT ubiquitin ligase). Despite a strong likelihood of association, episomal transfections demonstrated a role for the HECT ubiquitin-protein ligase in quinine and quinidine sensitivity in only a subset of genetic backgrounds, and here the changes in IC50 values were moderate (approximately 2-fold). These data show that quinine responsiveness is a complex genetic trait with multiple alleles playing a role and that more experiments are needed to unravel the role of the contributing factors.

Bevacizumab is associated with a higher gastrointestinal/genitourinary fistula or perforation risk in cervical cancer patients undergoing pelvic radiotherapy.

BACKGROUND: Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. OBJECTIVES: To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. SEARCH STRATEGY: In this meta-analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. SELECTION CRITERIA: Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. DATA COLLECTION AND ANALYSIS: Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I2) was used to assess heterogeneity. Egger's regression test with a two-tailed P value was used to evaluate publication bias. MAIN RESULTS: Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76-9.20] and OR 4.71 [95% CI: 1.51-14.70], respectively). CONCLUSIONS: The bevacizumab-containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab-associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.

Intrauterine adhesion.

Intrauterine adhesions (IUA) occurred in the reproductive-age women are a big economic and health problem, resulting in severe impairment of social, psychological and physical function of the female genital organs. IUA-related symptoms or signs are varied greatly from free of symptoms or ambiguous symptoms (an incidental finding during the intervention) to ceased menstruation and loss of fecundability. The underlying pathophysiology is not completely understood, but intrauterine damage with broken basal layers of the endometrium formatting scar tissues or fibrosis in the endometrium with subsequently causing partial or complete occlusion of the uterine cavity may be a well-accepted hypothesis. Previously, infection is the most common cause to develop IUA, but now, intrauterine surgery may be a critical cause contributing to the majority of cases of IUA. In the current review, update information about the etiology, epidemiology, pathophysiology, sequelae and prevention of IUA will be renewed. We emphasize the importance of awareness of IUA, and primary prevention should be considered in the routine clinical practice if intrauterine surgery has been applied, based on uncertainty of ideal treatment for the established IUA and unpredictable outcomes after IUA treatment. So far, evidence supports that hyaluronic acid with/without other strategy is the most valuable and effective method to reduce the formation and re-formation of IUA as well as to achieve the best fertility outcome.

Optimizing ensemble U-Net architectures for robust coronary vessel segmentation in angiographic images.

Automated coronary angiography assessment requires precise vessel segmentation, a task complicated by uneven contrast filling and background noise. Our research introduces an ensemble U-Net model, SE-RegUNet, designed to accurately segment coronary vessels using 100 labeled angiographies from angiographic images. SE-RegUNet incorporates RegNet encoders and squeeze-and-excitation blocks to enhance feature extraction. A dual-phase image preprocessing strategy further improves the model's performance, employing unsharp masking and contrast-limited adaptive histogram equalization. Following fivefold cross-validation and Ranger21 optimization, the SE-RegUNet 4GF model emerged as the most effective, evidenced by performance metrics such as a Dice score of 0.72 and an accuracy of 0.97. Its potential for real-world application is highlighted by its ability to process images at 41.6 frames per second. External validation on the DCA1 dataset demonstrated the model's consistent robustness, achieving a Dice score of 0.76 and an accuracy of 0.97. The SE-RegUNet 4GF model's precision in segmenting blood vessels in coronary angiographies showcases its remarkable efficiency and accuracy. However, further development and clinical testing are necessary before it can be routinely implemented in medical practice.

MPT0E028, a novel pan-HDAC inhibitor, prevents pulmonary fibrosis through inhibition of TGF-ß-induced CTGF expression in human lung fibroblasts: Involvement of MKP-1 activation.

Histone deacetylase (HDAC) inhibitors are potential candidates for treating pulmonary fibrosis. MPT0E028, a novel pan-HDAC inhibitor, has been reported to exhibit antitumor activity in several cancer cell lines. In this study, we investigated the mechanism underlying the inhibitory effects of MPT0E028 on the expression of fibrogenic proteins in human lung fibroblasts (WI-38). Our results revealed that MPT0E028 inhibited transforming growth factor-ß (TGF-ß)-, thrombin-, and endothelin 1-induced connective tissue growth factor (CTGF) expression in a concentration-dependent manner. In addition, MPT0E028 suppressed TGF-ß-stimulated expression of fibronectin, collagen I, and α-smooth muscle actin (α-SMA). Furthermore, MPT0E028 inhibited the TGF-ß-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). MPT0E028 reduced the increase in SMAD3 and c-Jun phosphorylation, and SMAD3-and activator protein-1 (AP-1)-luciferase activities under TGF-ß stimulation. Transfection with mitogen-activated protein kinase phosphatase-1 (MKP-1) siRNA reversed the suppressive effects of MPT0E028 on TGF-ß-induced increases in CTGF expression; JNK, p38, and ERK phosphorylation; and SMAD3 and AP-1 activation. Moreover, MPT0E028 increased MKP-1 acetylation and activity in WI-38 cells. Pretreatment with MPT0E028 reduced the fibrosis score and fibronectin, collagen, and α-SMA expression in bleomycin-induced pulmonary fibrosis mice. In conclusion, MPT0E028 induced MKP-1 acetylation and activation, which in turn inhibited TGF-ß-stimulated JNK, p38, and ERK phosphorylation; SMAD3 and AP-1 activation; and subsequent CTGF expression in human lung fibroblasts. Thus, MPT0E028 may be a potential drug for treating pulmonary fibrosis.

Impact of early bleeding on long-term mortality after left atrial appendage occlusion.

BACKGROUND: Short-term antithrombotic therapy is recommended after left atrial appendage occlusion (LAAO) to reduce the risk of device-related thrombosis. However, patients referred for LAAO have excess bleeding risk. Yet, short-term bleeding events post-LAAO are not well characterized. OBJECTIVES: We aimed to evaluate the incidence of early bleeding post-LAAO and its association with long-term mortality risk. We also sought to identify predictors of early bleeding. METHODS: Patients who underwent LAAO at Mayo Clinic between 2018 and 2023 were included. Early bleeding was defined as bleeding that occurred within 3 months of discharge. A multivariable Cox proportional hazards model was used to assess the association between early bleeding and death and to estimate the hazard ratio. Multivariable regression analysis was used to identify predictors of early bleeding. RESULTS: Of the 592 patients included, 389 (66%) were male, and the mean age was 75.6 years. Eighty-three patients (14.0%) experienced early bleeding, with the majority having minimal (63.4%) or minor (17.3%) bleeding. At a median follow-up of 14.4 months (interquartile range 4.2-27.9 months), early bleeding after LAAO was associated with an increased risk of all-cause mortality (adjusted hazard ratio 2.07; 95% confidence interval 1.15-3.75; P = .02). A history of intracranial bleeding, nonparoxysmal atrial fibrillation, CHA2DS2-VASc score, and early device-related thrombosis were independent predictors of early bleeding. Antithrombotic therapy at discharge was not associated with early nonprocedural bleeding. CONCLUSION: One in 7 patients experience a nonprocedural bleeding event within 90 days of LAAO. Early bleeding after LAAO is associated with a higher all-cause mortality risk during mid-term follow-up. Further studies are needed to optimize the management of patients undergoing LAAO.

The role of sialylation in gynecologic cancers.

Sialic acids (SA) are a kind of nine-carbon backbone sugars, serving as important molecules in cell-to-cell or cell-to-extra-cellular matrix interaction mediated by either O-linked glycosylation or N-linked glycosylation to attach the terminal end of glycans, glycoproteins, and glycolipids. All processes need a balance between sialylation by sialyltransferase (STs) and desialylation by sialidases (also known as neuraminidases, NEU). Although there is much in uncertainty whether the sialyation plays in cancer development and progression, at least four mechanisms are proposed, including surveillance of immune system, modification of cellular apoptosis and cell death, alteration of cellular surface of cancer cells and tumor associated microenvironment responsible carcinogenesis, growth and metastases. The current review focuses on the role of glycosylation in gynecologic organ-related cancers, such as ovarian cancer, cervical and endometrial cancer. Evidence shows that sialylation involving in the alternation of surface components of cells (tumor and cells in the microenvironment of host) plays an important role for carcinogenesis (escape from immunosurveillance) and dissemination (metastasis) (sloughing from the original site of cancer, migration into the circulation system, extravasation from the circulatory system to the distant site and finally deposition and establishment on the new growth lesion to complete the metastatic process). Additionally, modification of glycosylation can enhance or alleviate the aggressive characteristics of the cancer behaviors. All suggest that more understandings of glycosylation on cancers may provide a new therapeutic field to assist the cancer treatment in the near future.

Towards scanning nanostructure X-ray microscopy.

This article demonstrates spatial mapping of the local and nanoscale structure of thin film objects using spatially resolved pair distribution function (PDF) analysis of synchrotron X-ray diffraction data. This is exemplified in a lab-on-chip combinatorial array of sample spots containing catalytically interesting nanoparticles deposited from liquid precursors using an ink-jet liquid-handling system. A software implementation is presented of the whole protocol, including an approach for automated data acquisition and analysis using the atomic PDF method. The protocol software can handle semi-automated data reduction, normalization and modeling, with user-defined recipes generating a comprehensive collection of metadata and analysis results. By slicing the collection using included functions, it is possible to build images of different contrast features chosen by the user, giving insights into different aspects of the local structure.

Efficacy of the new adjustable I-stop-mini sling system in women with stress urinary incontinence and intrinsic sphincter deficiency: A retrospective cohort study.

OBJECTIVE: We aimed to evaluate the efficacy, surgical outcomes, and adverse events of the adjustable midurethral sling I-stop-mini in women with intrinsic sphincter deficiency (ISD)-type stress urinary incontinence. We compared this new sling system with the Obtryx transobturator midurethral sling system. METHODS: This retrospective cohort study was conducted at a single center from June 2017 to December 2020. A total of 141 women who underwent placement of an I-stop-mini or Obtryx and were followed up for at least 1 year were enrolled. ISD was defined as a Valsalva leak point pressure of ≤60 cmH2 O or a maximal urethral closure pressure of ≤20 cmH2 O. Student t test was used to compare continuous variables, and chi-square test was used to compare the distribution of categorical data. RESULTS: In terms of objective success, I-stop-mini and Obtryx showed no significant differences in the postoperative 1-month, 6-month, and 12-month. The two devices showed similar effectiveness regardless of the ISD definition. The I-stop-mini group had a significantly shorter operative time, whereas the adverse event rates were similar. CONCLUSION: The subjective cure rate, objective success, and adverse event rate did not differ in the two devices. I-stop-mini had a significantly shorter operative time.

Efficacy of minimally invasive pectopexy with concomitant I-stop-mini sling for women with pelvic organ prolapse and overt stress urinary incontinence: A retrospective cohort study.

OBJECTIVE: To compare the efficacy of minimally invasive pectopexy with I-stop-mini (MPI) and minimally invasive sacrocolpopexy with Obtryx (MSO). METHODS: Women with pelvic organ prolapse quantification (POP-Q) stage III or more and overt stress urinary incontinence from May 2018 to May 2021 were included. Patients with meshes fixed on the cervix or vaginal vault and bilateral pectineal ligament with I-stop-mini were classified into the MPI group, while those fixed on the apex and sacral promontory with Obtryx were classified into the MSO group. The primary outcomes were 1-year-postoperative POP-Q stage, patient-reported urinary and prolapse outcomes (Urogenital Distress Inventory-6, International Consultation on Incontinence Questionnaire-Short Form, and Pelvic Organ Prolapse Distress Inventory-6), 1-h pad test, and sexual life quality (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). Secondary outcomes included operative data and adverse events. RESULTS: The efficacy of MPI was similar to that of MSO according to the primary outcomes. MPI had shorter operative times (133.4 ± 30.6 min versus 199.3 ± 20.9 min, P = 0.001) and lower incidence rate of abdominal pain (0% vs 20%, P = 0.02) and groin pain (8% vs 40%, P = 0.01) than MSO. CONCLUSIONS: MPI showed similar efficacy to MSO, but demonstrated shorter operative times and lower incidence rates of abdominal and groin pain.